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Pediatric Brain Tumors and Implications for Physical Therapy

Pediatric Brain Tumors and Implications for Physical Therapy

12/15/2018

PEDIATRIC OBJECTIVES AND THE ROLE OF PHYSICAL THERAPY • Identify and describe common pediatric ALONG THE diagnoses. CONTINUUM OF CARE • Recognize the associated side effects of medical Stacey Caviston PT, DPT, PCS treatments for pediatric cancers and their Kristen DeVirgilio PT, DPT impact on function. Megan Ryninger PT, DPT, PCS January 25, 2019 • Develop and implement effective physical therapy examinations, treatment strategies, and overall plan(s) of care for pediatric patients in all stages of treatment. • Discuss the differences between pediatric and adult cancers.

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ADULT VERSUS PEDIATRIC CANCERS

• Pediatric cancers are not strongly linked to lifestyle factors

• Less health co-morbidities lend to improved GENERAL response and tolerance of treatment OVERVIEW • Cancer treatment can have long term side effects Pediatric Cancers • More inpatient admissions

COMMON PEDIATRIC CANCERS KEY STATISTICS

• • Pediatric cancers make up < 1% of all cancers • Brain and spinal cord tumors diagnosed each year • • Wilms tumor • An estimated 10,590 new cancer cases will be diagnosed among children 0 to 14 years of age in • Lymphoma (including both Hodgkin and Non the US in 2018. Hodgkin) • Rhabdomyosarcoma • Cancer is the second-leading cause of death • among children ages 1-14 years (after accidents), • Bone cancer (including osteosarcoma and Ewing accounting for 13% of deaths in 2015. )

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INCIDENCE RATES INCIDENCE RATES

American Cancer Society. Cancer Facts & Figures 2018. Atlanta: American Cancer Society; 2018. American Cancer Society. Cancer Facts & Figures 2018. Atlanta: American Cancer Society; 2018.

ETIOLOGY GENERALIZED

• Inherited familial syndromes • Unusual mass or swelling • type 1 • Paleness • Li-Fraumeni syndrome • Loss of energy • Genetic syndromes • Increase in or bruising • Down Syndrome • Persistent, localized pain or limping • Germline • Prolonged/unexplained fever • Environmental factors • Frequent often associated with • • Lifestyle factors • Sudden eye or vision changes • Not typically a factor in pediatric cases • Sudden unexplained weight loss

GENERAL DIAGNOSTIC TESTS STAGING

• Medical history and physical exam • Currently no national system for pediatrics • Blood tests • Bone marrow aspiration and • Staging systems vary by: • Lumbar puncture • Diagnosis • Biopsy • Trial group/current protocol • Chest x-ray • Computed tomography (CT) or positron emission tomography (PET) scan • Magnetic resonance imaging (MRI) • Ultrasound

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MEDICAL INTERVENTIONS

• Chemotherapy • Cytotoxic used to kill cancerous cells by: • Killing cancer cells • • Stopping cancer cells from dividing • Most common methods of administration: • • Oral • Intravenous • Intrathecal • Steroids • Malignant cancers receive multiple chemotherapy agents via individualized road maps

COMMON TYPES OF CHEMOTHERAPY CHEMOTHERAPY SIDE EFFECTS AGENTS Chemotherapy Agent Possible Side Effects Common Diagnoses

Vincristine Hair loss, peripheral neuropathy, constipation, low blood Acute leukemia, Hodgkin’s/non-Hodgkin’s • /vomiting counts, nausea, vomiting, mouth sores, diarrhea, loss of lymphoma, neuroblastoma, appetite, taste changes, abdominal cramping rhabdomyosarcoma, Ewing’s sarcoma, • Fatigue Wilms’ tumor, multiple • Fever myeloma, chronic , thyroid cancers, brain tumors, and some blood • Pain disorders • Hearing loss Low blood counts, nausea, vomiting, kidney toxicity, low Hodgkin’s/non-Hodgkin’s lymphoma, magnesium/potassium/calcium, peripheral neuropathy, neuroblastoma, • Anemia/neutropenia high frequency hearing loss, loss of appetite, taste changes, • Bruising/bleeding liver dysfunction, hair loss, changes in fertility • Diarrhea or constipation Etoposide Low blood counts, low platelet counts, hypotension, loss of Hodgkin’s and non-Hodgkin’s lymphoma, • Nerve/muscle effects fertility, nausea, vomiting, hair loss, mouth sores, diarrhea, Wilm’s tumor, rhabdomyosarcoma, Ewing’s poor appetite, nerve damage sarcoma, neuroblastoma, brain tumors, and • Secondary can be used for conditioning for bone marrow transplant • Hair loss • Mouth sores High dose methotrexate Low blood counts, mouth sores, poor appetite, nausea, Acute lymphoblastic leukemia, sarcomas, • Weight loss vomiting, kidney toxicity, kidney failure, skin rash, diarrhea, non-Hodgkin’s lymphoma, and cutaneous T hair loss, eye irritation, liver problems, radiation recall, loss of cell lymphoma • Infection fertility • Changes in appetite Doxorubicin Heart damage, fatigue, nausea, vomiting, mouth sores, bone Soft and bone sarcomas, acute marrow suppression lymphoblastic leukemia, acute myeloid leukemia, Hodgkin lymphoma Ifosfamide Damage to lining of bladder, mouth sores, nausea, vomiting, Soft tissue and bone sarcoma nerve damage, , hair loss

RADIATION THERAPY TYPES OF RADIATION

• Use of high energy particles or waves to destroy cancer cells by inhibiting cell growth and X-ray/photon Proton division • Total brain irrigation • Targets tumor at • Deposit energy in higher intensity • Method of administration depends on type and small packets along • Depth of energy is stage of cancer their path through the released and can be • External tissue controlled • Internal • Can damage healthy • Fewer short term and • Systemic tissue long term side effects • Decreases risk of secondary malignancies

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RADIATION THERAPY GENERAL SIDE DOSE DISTRIBUTION EFFECTS

• Fatigue

• Hair Loss

• Integumentary changes

• Immunosuppression

Fowler JF. What can we expect from dose escalation using proton beams? Clin Oncol. 2003;15(1):S10-S15. • Secondary malignancies

TYPES OF SURGERY

• Biopsy • Curative • Palliative • Gross total resection • Relieve pain • Clear margins • Minimize symptoms • Gross total resection versus partial resection • Improve quality of life • Reconstruction

• Limb salvage

• Amputation

SURGICAL SIDE EFFECTS STEROIDS

• Pain • are man-made drugs that work like cortisol, a natural hormone in your body. • Fatigue • Appetite loss • Prescribed as part of treatment or as a • Integumentary changes supportive measure • Numbness • Bleeding • Common corticosteroids used in pediatric • Infection cancer treatment: • Physical impairments • • Prednisone • Cognitive impairments

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STEROID SIDE EFFECTS PEDIATRIC CANCER PROGNOSIS

• Increased appetite • The 5-year relative survival for the most recent time • Weight gain period (2007-2013) is 83%, although rates vary considerably depending on cancer type, patient age, and • Muscle weakness other characteristics. • Mood swings • Depends on several factors including: • Nausea • Type of tumor • Insomnia • Location of tumor • High glucose levels • Grade of tumor • High blood pressure • Staging • Avascular (AVN) • Speed of growth • Hearing loss • Treatment options • Age of child • Immunosuppression • survivors can experience late and long • Gastrointestinal issues term effects from treatment in a variety of body systems.

BONE MARROW, STEM CELL, AND SURVIVAL RATES CORD BLOOD TRANSPLANTS

• Healthy marrow or stem cells are infused into pt’s blood stream

• Goal of transplant is engraftment

• Indications • Patients with relapsed ALL and AML • Patients with life threatening disease • Patients with Neuroblastoma • Some patients with brain tumors

American Cancer Society. Cancer Facts & Figures 2018. Atlanta: American Cancer Society; 2018.

BONE MARROW, STEM CELL, AND TRANSPLANT PROCESS CORD BLOOD TRANSPLANTS

• Types of Transplant • Pre-transplant conditioning • Bone Marrow • High doses of chemo and or radiation • Stem Cells • Umbilical Cord Blood • Transplant • Cells are administered • Source of cells • Allogenic - Donor • Post-transplant • Autogenic - Self • Await engraftment • Syngenic - Identical twin • Usually 12-17 days

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BONE MARROW AND STEM CELL TRANSPLANT – SIDE EFFECTS

• Graft vs. Host Disease (GVHD) • Mucositis • Nausea/Vomiting • Venous Occlusive Disease (VOD) • Steroid induced myopathy • Sterility SOLID TUMORS • Cardiac and pulmonary disease • High risk of life threatening infection • Secondary malignancies

COMMON DIAGNOSES OSTEOSARCOMA

• Osteosarcoma • Tumor cells arise from osteoblast cells and • Ewing’s Sarcoma primarily affect the ends of the long bones • Rhabdomyosarcoma • Most common malignant in children • Neuroblastoma and adolescents • ~ 400 new pediatric cases each year in the United States • ~ 2% of childhood cancers

• Common sites: • Distal femur • Proximal tibia • Proximal humerus

OSTEOSARCOMA SIGNS AND OSTEOSARCOMA STAGING SYMPTOMS • Pain • Simplified • Stiffness or tenderness • Local • Progressively worse over time • Resectable • Wakes from sleep • Non-resectable • Swelling • Metastatic • Musculoskeletal Tumor Society (MSTS) staging • Palpable mass in arm or leg system • Difficulty walking or limp • Grade (G) Stage Grade Tumor • Fracture • Extent of (T) IA G1 T1 M0 • Metastases (M) • Fatigue IB G1 T2 M0 • TNM staging system IIA G2 T1 M0 • Weight loss • (T) Tumor IIB G2 T2 M0 G1 or T1 • Anemia • (N) Nodes III M1 • (M) Metastasized G2 orT2 • (G) Grade

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OSTEOSARCOMA TREATMENT OSTEOSARCOMA PROGNOSIS

• Chemotherapy: Total 6 cycles • Positive Prognostic Factors • Neoadjuvant: Prior to surgery or radiation • 2 cycles • Younger age • Adjuvant: Continues after surgery/radiation • Female • Common chemotherapy agents: • Distal primary tumor site • Methotrexate • Doxorubicin • Complete tumor resection • Cisplatin • Good tumor necrosis following chemotherapy • Ifosfamide • Etoposide • Surgery • 5 year survival rate • Goal: to remove all cancer cells (negative margins) • Localized: 60-80% • Limb Salvage • Amputation • Metastatic: 15-30% • Time frame of surgery: Week 11 • Improved to ~ 40% if only metastasis is to lungs • Improved survival if tumor and all metastases can be • Radiation surgically removed • Not very sensitive to radiation • Used when positive margins left following surgery • Symptom control in recurrent tumors

EWING’S SARCOMA SIGNS AND EWING’S SARCOMA SYMPTOMS • Malignant small, round, blue cell tumor starting • Pain in the bones or surrounding soft tissue • Stiffness or tenderness • Progressively worse over time • Wakes from sleep • Second most common malignant bone tumor in • Swelling children and adolescents • Palpable mass • ~ 200 new cases each year in the United States • Difficulty walking or limp • ~ 1% of childhood cancers • Fracture • Fatigue • Common Sites: • Weight loss • Pelvis • Chest wall (ribs and scapula) • Anemia • Legs (middle of long bones)

EWING’S SARCOMA STAGING EWING’S SARCOMA TREATMENT

• Simplified • Chemotherapy: Total of 6 cycles • Local • Each cycle includes: • Metastatic • Vincristine, doxorubicin, • American Joint Committee on Cancer (AJCC) staging system – TNMG • Ifosfamide, etoposide • (T) Tumor • Neoadjuvant: Prior to surgery or radiation • T0: No evidence of primary tumor • 3 cycles • T1: Tumor is no more than 8 cm across • Adjuvant: Continues after surgery/radiation • T2: Tumor is larger than 8 cm across • T3: Tumor is in more than one site in the same bone • Surgery • (N) Nodes • Goal: to remove all cancer cells (negative margins) • N0: No spread to nearby lymph nodes • Depends on size and location of tumor • N1: Spread to nearby lymph nodes • Arms/Legs: limb sparing versus amputation • (M) Metastasis • Proximal tumors: more complicated • M0: No metastasis • Time frame of surgery: • M1a: Metastasis to lungs only • Following 3 cycles of chemotherapy/Week 13 • M1b: Metastasis to other parts of the body • (G) Grade • Radiation • GX: Grade can not be assessed • Ewing’s tumors are very sensitive to radiation • G1: Low grade • G2-G3: High grade • Used as primary local control or in conjunction with surgery • All Ewing tumors are considered G3

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EWING’S SARCOMA PROGNOSIS RHABDOMYOSARCOMA (RMS)

• Aggressive tumor that develops from skeletal muscle cells that have • Positive Prognostic Factors failed to fully differentiate • Smaller tumor size • Small, round, blue cell tumor • Distal tumor site (arm/leg versus chest wall or pelvis) • Incidence: 400-500 new cases each year in United States • Tumor response to chemotherapy • ~ 3% of childhood cancers • More common in males • Younger age (< 10 years old) • More common in children < 10 years old

• Embryonal Rhabdomyosarcoma (ERMS) • Common in children 0-5 years old • 5 year survival rate • Common in head/neck and urogenital tract • Localized: 70% • Metastatic: 30% • Alveolar Rhabdomyosarcoma (ARMS) • Effects all age groups equally • Common in large muscles of trunk arms and legs

RHABDOMYOSARCOMA SIGNS RHABDOMYOSARCOMA STAGING AND SYMPTOMS • Depends on location of tumor • 3 part staging: • Eye: vision, eye bulging, oculomotor control • TNM staging system • Sinuses: earache/, nosebleeds, congestion • (T) Tumor • Urogenital: bleeding, painful or difficulty with voiding • (N) Nodes or bowel movement • (M) Metastasized • Abdomen/pelvis: vomiting, pain, constipation • Above factors combined to determine stage (1-4) • Clinical Group: I-IV • Lump or swelling • Based on extent of disease and initial tumor resection • Bone pain • PAX/FOX01 gene present or absent on tumor cells • Weakness • Risk Group: • Weight loss • Determined based on above 3 factors • Risk group determines treatment plan • Low, Intermediate, High

RHABDOMYOSARCOMA RHABDOMYOSARCOMA TREATMENT PROGNOSIS • Surgery • 5 year survival rate • Typically first step in treatment (based on location, function or metastatic disease) • Low risk: 70-90% • Chemotherapy • Intermediate risk: 50-70% • Low Risk • VA: vincristine and dactinomycin • High risk: 20-30% • Intermediate Risk: • VAC: vincristine, dactinomycin, and cyclophosphamide • VAC/VI: vincristine, dactinomycin, and cyclophosphamide, • Positive prognostic factors alternating with vincristine and irinotecan • High Risk: • Age: 1-9 years old • VAC or clinical trials • Tumor size < 5cm • Radiation • Gross total resection with negative margins • Typically used when some of the primary tumor is present after surgery • Absence of PAX/FOX01 gene • Used if resection would result in loss of vital organ or dysfunction

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NEUROBLASTOMA SIGNS AND NEUROBLASTOMA SYMPTOMS • Cancer that start in neuroblasts of the • Lump/swelling in abdomen or neck sympathetic nervous system • Swelling of the legs or upper chest, neck and face • Enlarged belly • Problems breathing or swallowing • Most common cancer in infants • Weight loss • ~ 6% of all childhood cancers • Complaining about feeling full • ~ 800 new cases each year in the United States • Problems with bowel movements or urinating • 90% of cases diagnosed prior to 5 years of age. • Pain in bones • Lumps or bumps in the skin that may appear blue • Problems being able to feel or move parts of the body • Opsoclonus-- syndrome

NEUROBLASTOMA STAGING NEUROBLASTOMA TREATMENT

• International Neurobalstoma Risk Group Staging • Treatment plan based on risk group System (INRGSS) • Surgery • Uses results from imaging tests • Biopsy • Resection if possible • Can be determined prior to start of treatment • Chemotherapy • 4 stages • Used prior to and following surgery • L1, L2, M, MS • Radiation • International Neuroblastoma Staging System • Not a common intervention for neuroblastoma • Used in high risk group following stem cell transplant or for symptom management (INSS) and to treat life threatening symptoms • Uses results from tumor resection to determine stage • High dose chemotherapy and stem cell transplant (SCT) • • High risk group Children’s Oncology Group (COG) risk groups • Tandem SCT • Low risk • Used to repair bone marrow from intense chemotherapy treatment • Intermediate risk • Immunotherapy • High risk: • Monoclonal antibodies injected into the body to seek out and attach to cancer cells • MIBG • Highly radioactive from injected into the blood and delivers local radiation to neuroblastoma cells • Requires hospital admission in special environment

SURGICAL MANAGEMENT OF SOLID NEUROBLASTOMA PROGNOSIS TUMORS IN THE EXTREMITIES

• Positive prognostic factors • Younger age (< 12-18 months) • Favorable tumor histology • Limb salvage • Low DNA index • Endoprosthetic placement • Absence of MCYN gene amplifications • Vascularized autologous bone graft • No changes to tumor cells • Allograft • Presence of neurotrophin receptors

• 5 year survival rate • Amputation • Low risk: 95% • Upper and lower extremity options • Intermediate risk: 90-95% • Rotationplasty • High risk: 40-50%

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COMMON DIAGNOSES

• Leukemia

• Lymphoma LIQUID TUMORS

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LEUKEMIA LEUKEMIA SIGNS AND SYMPTOMS

• Fever and unexplained infection • Cancer of the blood and bone marrow • Fatigue and generalized weakness • Bruising and bleeding (petechiae) • Cancer cells divide rapidly and live longer than • Bone and/or joint pain healthy cells so take over the space leaving little to no room for healthy WBC, RBC, and platelets • Abdominal pain due to enlarged liver or spleen • Swollen lymph nodes • Incidence • Decreased appetite/weight loss • Most common type of pediatric cancer • Accounts for 29% of all childhood cancers

www.healio.com

ACUTE LYMPHOBLASTIC LEUKEMIA LEUKEMIA (ALL)

• B-Cell – 85% • Types of Leukemia • Early Pre-B Cell • Acute Lymphoblastic • Pre-B Cell Leukemia (ALL) • B-Cell (Burkitt’s Lymphoma) • T-Cell • B-Cell • T-Cell – 15% • Acute Myeloid Leukemia (AML) • Peak age for diagnosis is 2 – 4 years old • Classification - Acute versus Chronic • Acute – blast cells • Incidence - accounts for 80% of pediatric • Chronic – mature/ leukemia diagnoses abnormal cells

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ALL STAGING ALL TREATMENT

Risk Group Age at Diagnosis Criteria • Chemotherapy

Standard Risk (SR) 1 – 9 years old White Blood Cell (WBC) Count at Diagnosis • Radiation < 50,000/µL High Risk Less than 1 year old White Blood Cell (WBC) Count at Diagnosis Greater than 10 years ≥ 50,000/µL • Transplant old • Relapsed disease

Very High Risk Less than 1 year old Children with slow response to with specific cyto- treatment gentics • Chimeric Antigen Receptor Therapy (CAR-T) Children with signs of leukemia after the first 4 weeks of treatment

*Children with T-Cell ALL are classified in a higher risk group

ALL PHASES OF CHEMOTHERAPY ALL RADIATION THERAPY TREATMENT

ALL - Standard Risk ALL - High Risk • A minority of children with ALL require Induction ~ 1 month ~ 1 month radiation therapy

Consolidation ~1-2 months ~ 2 months • Possible indications

Interim Maintenance ~ 1-2 months ~ 2 months • ALL that has spread to the brain, or testicles • In preparation for bone marrow transplant Delayed Intensification ~ 2 months ~ 2 months

Maintenance End of DI until ~ 2 years from End of DI until ~ 2 years from • Timing of radiation is variable start of therapy start of therapy

CAR-T OVERVIEW

• Targeted immunotherapy that genetically modifies a patient's T-cells so they will attack certain proteins on the surface of cancer cells

CHIMERIC ANTIGEN • Goal is proliferation and persistence of engineered RECEPTOR THERAPY T cells (CAR-T) • Indications: • Relapsed or refractory B-cell ALL • B-cell non Hodgkin's lymphoma

• Types • CAR-T 19 – targets CD 19 on • Other receptor numbers are currently being investigated

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CAR-T PROCESS CAR-T • T-Cell harvest from patient through leukophoresis • Cells are manufactured in the lab with vector • During this time the patient undergoes bridging chemotherapy

• Infusion Process • Lymphodepleting chemotherapy for a week • Preinfusion studies completed (bone marrow aspirate and biopsy, diagnostic lumbar pucture) • Infusion of CAR-T Cells

• Ongoing Monitoring • Diagnostic testing at day 28 and then every 3 months for the first year • Positive idicators • CAR-T cells in peripheral blood, bone marrow, and CSF • Lack of cancer cells • Lack of B-Cells

CAR-T SIDE EFFECTS ALL PROGNOSIS

• Cytokine Release Syndrome (CRS): systemic inflammatory response • Positive prognostic factors • Common Side Effects - High fever, Myalgias, Headaches, Nausea, and • Greater than 1 year old and less than 10 years old at diagnosis Fatigue • WBC less than 50,000/µL at diagnosis • More Serious Side Effects – Hypotension, Vascular leak leading to • No CNS involvement at diagnosis respiratory compromise, Renal insufficiency, and Coagulopathy • Cyto-genetics testing (ex Philadelphia chromosome negative indicator) • Fever • Initial response to treatment • Infection • B-Cell aplasia • 5 year survival rate - 91% • Neurological side effects • Headaches • •

ACUTE MYELOID LEUKEMIA (AML) AML TREATMENT

• Types • Chemotherapy • M0 – M7 based on cell type as determined by BMA at diagnosis

• Peak ages of diagnosis are 0-2 years old and • Monoclonal Antibody Therapy adolescence • Transplant • Staging – high risk if do not achieve remission • Patients with a sibling match • Patients with relapsed disease after induction or AML is relapsed • Patients with unfavorable cyto-genetics

• Incidence - accounts for 20% of all pediatric leukemia diagnoses

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AML PHASES OF CHEMOTHERAPY MONOCLONAL ANTIBODY THERAPY TREATMENT

• Induction • Antibodies are used to deliver drugs and • ~1 month long to cancer cells • Repeated every 10 days to 2 week until bone marrow is leukemia free, usually 2-3 cycles • Antibodies attaches to a protein found on the • Consolidation (Intensification) surface of many AML cells • Typically 3 cycles, each 28 days long

• Used in combination with chemotherapy to improve the long-term survival

MONOCLONAL ANTIBODY THERAPY SIDE EFFECTS AML PROGNOSIS

• Low blood counts • Positive prognostic factors: • Greater than 1 year old at diagnosis and less than 10 years old at • Nausea diagnosis • Vomiting • WBC less than 10,000/µL at diagnosis • Cyto-genetics testing • Headache • Initial response to treatment • Loss of appetite • Lower BMI • Fever and chills (most common with first dose) • Fatigue • 5 year survival rate - 65% • Venous Occlusive Disease (VOD)

LYMPHOMA LYMPHOMA SIGNS AND SYMPTOMS

• Cancer of the • Swelling of lymph nodes • Can present as solid tumors of lymph nodes • Mediastinal mass • Types • Difficulty breathing • Hodgkin Lymphoma • Weight loss • Non-Hodgkin Lymphoma • Night sweats • Incidence • Fatigue • 3rd most common type of childhood cancer • 8% of all childhood cancers • Fever • More common in boys than girls

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HODGKIN LYMPHOMA HODGKIN LYMPHOMA STAGING

• Diagnosed based on presence of Reed-Sternberg Cells

• Peak age of diagnosis is 15-19 years old

• Incidence - 10% of all pediatric lymphoma diagnoses

https://www.lls.org/lymphoma/hodgkin-lymphoma/diagnosis/hodgkin-lymphoma-staging

HODGKIN LYMPHOMA TREATMENT HODGKIN LYMPHOMA PROGNOSIS

• Chemotherapy • Positive Prognostic Factors • Lack of metastasis • Lack of B symptoms • Radiation • unexplained fever • drenching night sweats • unexpected weight loss • Response to treatment • Transplant

• 5 year survival rate - 98%

NON-HODGKIN LYMPHOMA NON-HODGKIN LYMPHOMA STAGING

Stage • Types Stage I Cancer is in one group of lymph nodes • Small B-Cell Lymphoma (Burkitt’s Lymphoma) • Lymphoblasitc Lymphoma (T-Cell Lymphoma) Stage II Tumor present in two or more lymph node areas on the • Large cell Lymphoma same side of the diaphragm

• Peak age of diagnosis is adolescence Stage III Tumor on both sides of the diaphragm

Stage IV Tumor has spread from original location to bone marrow or • Incidence - 90% of all pediatric lymphoma (brain or spinal fluid) diagnoses

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NON-HODGKIN LYMPHOMA TREATMENT NON-HODGKIN LYMPHOMA PROGNOSIS

• Chemotherapy • Positive Prognostic Factors • Lack of metastasis • Lack of B symptoms • Surgery (Burkitt’s) • unexplained fever • drenching night sweats • unexpected weight loss • Monoclonal Antibody Therapy • Response to treatment

• 5 year survival rate –91% • Transplant

CLASSIFICATION OF BRAIN TUMORS BRAIN TUMORS

CLASSIFICATION OF BRAIN TUMORS CLASSIFICATION OF BRAIN TUMORS

Secondary Primary (Metastatic) Benign • Malignant • Originate from • Originate from cells • Typical of the cell of • Cell of origin with normal cells within outside of the central origin greater differentiation the brain nervous system • Decreased mitosis • Increased mitosis • Name includes cell of (CNS) • Fast growing/high • Slow growing/low grade origin with or without • Always malignant grade location • Invade surrounding • Localized brain tissues • Benign or malignant • Well defined borders • Metastasize outside of the CNS

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WORLD HEALTH ORGANIZATION (WHO) GRADES Grade Characteristics Tumor Types Low Grade Grade I •Least malignant (benign) •Possibly curable via surgery alone •Non-infiltrative •Long-term survival •Slow growing CLINICAL Grade II •Relatively slow growing •Somewhat infiltrative •May recur as higher grade PRESENTATION High Grade Grade III •Malignant •Infiltrative •Tend to recur as higher grade Grade IV •Most malignant •Rapid growth, aggressive •Widely infiltrative •Rapid recurrence •Necrosis prone

GENERALIZING SYMPTOMS LOCALIZING SYMPTOMS

• Increased (ICP) • Headache, nausea, vomiting, fatigue • Decreased upgaze, sixth cranial nerve palsies, • Infants: macrocephaly, failure to thrive, developmental delay • Ataxia • “Flu-like” symptoms • Cranial nerve deficits • Cognitive deficits or changes in school performance • Mental status changes

• Seizures Jain, V. Brain Tumor. Slide Share website. https://www.slideshare.net/jvyom001/brain-tumor- 68206369. November 4, 2016. Accessed November 1, 2018.

COMMON DIAGNOSES

• • • TYPES OF TUMORS • Brain stem

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TYPES OF TUMORS ASTROCYTOMA

• Incidence: • 35% of childhood brain tumors • 80% are low grade • Most common in children 5-8 years old

• Location: • Can occur anywhere in the central nervous Cerebellar . Clinical Gate website https://clinicalgate.com/cerebellar-astrocytomas/. March 26, system (CNS) 2015. Accessed November 1, 2018.

Brain Tumors. Children’s Hopsital of Wisconsin website https://www.chw.org/medical-care/macc-fund- center/conditions/oncology/brain-tumors. Accessed November 1, 2018.

ASTROCYTOMA SCALE ASTROCYTOMA TREATMENT

Grade • Depends on location and grade of tumor • Low grade Low Grade I Juvenile pilocytic • Surgery is primary therapy astrocytoma (JPA) • Management of residual tumor: II Diffuse astrocytoma • Observation • Re-resection High Grade III • Radiation therapy

IV • High grade multiforme (GBM) • Surgery • Radiation therapy

ASTROCYTOMA PROGNOSIS MEDULLOBLASTOMA • Prognostic factors • Low grade • Incidence: • Young age • 18-20% of primary • Subtotal resection CNS tumors • >70% occur in • 5 year survival rates children less than 10 • Low grade years old • 97% for pilocytic • Slightly more • 80-85% for diffuse common in males • High grade • 25% for anaplastic • 20% for GBM • Location: • Gaillard, F. Medulloblastoma. Radiopaedia website https://radiopaedia.org/articles/medulloblastoma. Accessed November 1, 2018.

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MEDULLOBLASTOMA STAGING MEDULLOBLASTOMA TREATMENT

Standard Risk High Risk • Surgery

Age >/= 3 years old < 3 years old • Radiation therapy Location Cerebellum Supratentorial • Chemotherapy Residual Tumor < 1.5 cm2 >/= 1.5 cm2

Metastases No Yes • Bone/stem cell transplant

Slide courtesy of Cindy Schmus

MEDULLOBLASTOMA PROGNOSIS EPENDYMOMA

• Prognostic factors • Subtotal resection • Incidence: • Patient age: < 3 years old • 9-10% of childhood brain tumors • Location: supratentorial • Metastasis • Location: • 5 year survival rates • Supratentorium • Standard Risk: 70-80% • Infratentorium • High Risk: 60-65% • Spinal • Infants: 30-50%

Ependymoma. Pediatric Oncology Education Materials website http://www.pedsoncologyeducation.com/ependymoma_location.asp. Accessed November 1, 2018.

EPENDYMOMA TREATMENT EPENDYMOMA PROGNOSIS

• Surgery – aggressive resection • Prognostic factors • Subtotal resection • Histology: anaplastic • Radiation therapy • Metastasis • Younger age at diagnosis • Chemotherapy • Location

• 5 year survival rates • Observation – in rare cases • Birth to 19: 75%

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BRAIN STEM GLIOMA BRAIN STEM GLIOMA

• Based on type: • Incidence: • Focal: • 10% of pediatric brain • Observation (with or without diversion) tumors • Surgical resection • in the form of radiation therapy or chemotherapy in select circumstances • Location: • 80% occur in the pons • Diffuse intrinsic: • Radiation therapy – standard of care • Types: • Diffuse intrinsic

Brain Stem Glioma. Brain Tumour Foundation of Canada • Focal website https://www.braintumour.ca/4884/brainstem-glioma. Accessed November 1, 2018.

BRAIN STEM GLIOMA PROGNOSIS PROGNOSIS

• Prognostic factors • Type: Diffuse intrinsic • Location in pons ASTROCYTOMA • Age: > 3 years of age with diffuse intrinsic PNET

• 5 year survival rates EPENDYMOMA • Based on location: • Focal: >90% 5 year survival rate GLIOMA • Pons: median survival rate < 1 year 0% 5 YEAR SURVIVAL RATES 100%

Slide courtesy of Cindy Schmus

ADULT VERSUS PEDIATRIC CONSIDERATIONS

• Children are not small adults • Children react differently to treatments • Children heal more quickly • Children are undergoing periods of rapid growth and PHYSICAL THERAPY development MANAGEMENT • Children will be active if they feel good

• Family centered care

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MEDICAL CONSIDERATIONS GENERAL CONSIDERATIONS

• Lab values Patient Family • Medical status • Level of coping • Treatment effects

• Cognitive status • Dynamics • Lines and tubes

• Chronological/ • Resources/supports • General anesthesia effects developmental age

• Level of coping

AGE RELATED CONSIDERATIONS

• Baseline developmental abilities

• Use of preferred play and leisure activities EXAMINATION History, Review of Systems, Tests and Measure

PAIN HISTORY

• Pain Scales • Numerical rating scale Objective Subjective • > 8 years of age • Medical history • Social • FLACC • 2 months to 7 years • Imaging • Developmental • Wong-Baker Faces • Operative reports • Home set up • 3 years and up • Medications • Equipment • Consider • Red flags • Schooling/Daycare • Impact of pain on other assessment areas • Impact of arousal level/cognition on ability to communicate pain • Individualized response

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REVIEW OF SYSTEMS

• Cardiovascular

• Integumentary

• Musculoskeletal CARDIOVASCULAR

• Neuromuscular SYSTEM

TESTS AND MEASURES FOR BODY NORMAL CARDIORESPIRATORY STRUCTURE AND FUNCTION PARAMETERS

• Monitor heart rate • Monitor oxygen saturation • Monitor blood pressure • Chest wall shape • Chest wall mobility • Breathing pattern • Tolerance to activity/rate of perceived exertion • Endurance • Fatigue levels

Values courtesy of the Children’s Hospital of Philadelphia

IMPAIRMENTS COMMONLY ASSOCIATED WITH TREATMENT DECONDITIONING/FATIGUE

• Deconditioning • Due to treatment, prolonged • PT Assessment: admissions, abnormal blood • General cardiopulmonary tests • Cancer related fatigue counts and measures • Standardized tests: • 6 minute walk test • Pulmonary complications from treatment • 3 minute step test

• PT Interventions:

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LATE EFFECTS PULMONARY COMPLICATIONS

• Heart disease • Due to radiation therapy to • PT Assessment: • Arrhythmia the chest or total body • Chest wall measurements in irradiation; complication of various positions • Hypertension bone marrow transplant • Posture • Reduced lung function • Shoulder range of motion (ROM) • Dyspnea • Common diagnoses: • Hamstring flexibility • Pulmonary fibrosis • Radiation pneumonitis • Strength assessment specifically core and proximal • Constant cough • Pulmonary fibrosis musculature • Lung graft versus host • Pulmonary pneumonitis disease (GVHD) • Increased risk of lung infections • Bronchiolitis obliterans • PT Interventions: • Increased risk for

TESTS AND MEASURES FOR BODY STRUCTURE AND FUNCTION

• Wound characteristics • Scar characteristics: • Location • Location • Wound bed margin • Size description • Color INTEGUMENTARY • Drainage/exudate • Moisture: description • Elastic Turgor • Integrity of Tissues • Wound type SYSTEM • Mobility of scar • Depth of tissue destruction • Tissue color • Infection • Photo documentation

IMPAIRMENTS COMMONLY WOUND PREVENTION ASSOCIATED WITH TREATMENT

• Assess risk for skin injury • Scar adhesion • Graft versus host disease (GVHD) • Consider • Radiation changes/burns • Bony prominences • Poor wound healing • Impact of immobility • Sensation

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GVHD OVERVIEW SCAR ADHESION

• Potential complication of allogenic transplants • Due to surgical • PT Assessment: intervention • Modified Vancouver scale • Types • Acute • Skin • PT Interventions: • Liver • Gastrointestinal tract (stomach, intestines, colon) • Chronic • Single organ to widespread

• Common medical management includes steroids

GVHD CLASSIFICATION SKIN GVHD PT MANAGEMENT

• Assessment: • Interventions: • Skin injury prevention • ROM • Positioning • Posture • Mobility • Joint play • Flexibility

TESTS AND MEASURES FOR BODY STRUCTURE AND FUNCTION

• ROM • Strength MUSCULOSKELETAL • Posture SYSTEM • Mobility

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RANGE OF MOTION RANGE OF MOTION

https://www.semanticscholar.org/topic/Active-Range-of-Motion/274568

STRENGTH POSTURAL ASSESSMENT

• Observation • Common postural changes • Head preference • Elevated shoulders • Kyphosis • Gravity dependent positioning • Foot and ankle alignment

COMMON IMPAIRMENTS ASSOCIATED MOBILITY WITH TREATMENT

• Developmental transitions • Chemotherapy induced peripheral neuropathy • Functional transfers (CIPN) • Gross motor skill assessment • Steroid myopathy • Gait assessment • Avascular necrosis (AVN) • Stair negotiation assessment • Orthopedic post operative complications • Bone instability • Pathologic fractures • Bone density

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CIPN OVERVIEW CIPN SIGNS AND SYMPTOMS

• Damage to peripheral nerves as a side effect of • Pain chemotherapy treatment • Burning • Vincristine, cisplatin • Tingling • Loss of sensation • Incidence • Balance problems • Difficulty walking/climbing stairs • Increased sensitivity to temperature/touch/pressure • Muscle atrophy • Muscle weakness • Diminished or absent reflexes • Audible foot slap

CIPN PT ASSESSMENT CIPN PT INTERVENTIONS

• Ankle dorsiflexion ROM • Great toe extension and tibialis anterior muscle strength • Popliteal angle • Achilles reflex • Sensation/vibration • Foot posture/alignment • Balance • Gait • Standardized tests: • Ped-mTNS • Pediatric balance scale

CIPN PROGNOSIS STEROID MYOPATHY OVERVIEW

• Insidious disease process that causes weakness to the proximal muscles of the upper and lower extremities

• Signs and symptoms: • Symmetric, proximal muscle weakness • Malaise • Fatigue • Absence of sensory complaints

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STEROID MYOPATHY PT AVN MANAGEMENT

• Assessment: • Interventions: • Death of bone tissue • PT Assessment: • General due to lack of blood • General musculoskeletal test supply musculoskeletal tests and measure with and measures focus on proximal • Pain musculature • Side effect of steroid • Mobility treatment

• PT Interventions:

ORTHOPEDIC POST OPERATIVE ORTHOPEDIC POST OPERATIVE COMPLICATIONS OVERVIEW COMPLICATIONS PT MANAGEMENT • Due to surgery for localized treatment • • Assessment • Common complications: • General • Pain musculoskeletal tests • ROM deficits and measures • Weakness • Immobility • Altered sensation • Leg length discrepancies • Nerve damage • Postural abnormalities • Altered gait mechanics • Wound dehiscence/infection • Hardware failure • Repeat surgeries

INTERVENTIONS LATE EFFECTS

• Stunted growth • Bone pain • Joint stiffness • Decreased bone density • Gait alterations

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TESTS AND MEASURES FOR BODY STRUCTURE AND FUNCTION

• Muscle tone • Sensation NEUROMUSCULAR • Reflexes • Level of arousal • Balance • Cognition SYSTEM • Coordination • Cranial nerve testing • Proprioception • Vision/hearing

COMMON IMPAIRMENTS ASSOCIATED POSTERIOR FOSSA SYNDROME WITH TREATMENT OVERVIEW

• A postoperative syndrome involving a variety of • Posterior fossa syndrome clinical characteristics • Neurological • Neuropsychological • Ataxia • Neurolinguistic • Incidence: Reports vary from 2-50% • Spasticity • Onset: Varies from 24-107 hours post operatively • Hemiplegia • Duration: Weeks to months

POSTERIOR FOSSA SYNDROME SIGNS POSTERIOR FOSSA SYNDROME PT AND SYMPTOMS MANAGEMENT

Motor Cognitive Affect/Behavior Speech/Language • Assessment: • Interventions: • Ataxia • Attention • Depression • Cerebellar mutism • Dysmetria • Memory • Irritability • Naming problems • General • Dysphagia • Executive • Lability • Verbal fluency neuromuscular tests • functioning • Apathy • Dysarthria • Hypotonia • Visuospatial skills • Anxiety • Slowed speech and measures • • Processing speed • Forced • Decreased verbal • Speech and language • • Verbal crying/laughter output • Oculomotor comprehension • Transient eye • Short phrases screening problems • Reading/writing closure • Distorted vowels • Urinary difficulties • Impulsivity • Prolonged • Cognitive screening retention/incontin phonemes ence • Mono- • Affect and behavior pitch/loudness • Hypernasality screening • Vocal

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POSTERIOR FOSSA SYNDROME PROGNOSIS ATAXIA OVERVIEW

• Lack of voluntary coordination of muscle movements

ATAXIA PT MANAGEMENT SPASTICITY

• Assessment • Interventions • Due to damage of the • PT assessment: • Ataxia rating scale nerves in the central • Modified Ashworth nervous system. Score • Mobility • Altered muscle • ROM measurements movement patterns • Mobility and ADL’s with hypertonia and increased tendon reflex • PT interventions: activity • Managed with oral medications, local injections or intrathecal baclofen

LATE EFFECTS

• Neurocognitive impairments • Lower IQ scores • Poor attention/memory • Poor hand eye coordination • Behavioral problems • Developmental delay • Pituitary issues EVALUATION • Seizures Diagnosis, Prognosis, Plan of Care • Headaches

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CANCER REHABILITATION ACROSS THE DIAGNOSIS AND PROGNOSIS CONTINUUM

• PT Diagnosis • Based on impairments

• Prognosis depends on: • Type of cancer Re- End of • Grade/stage of cancer Diagnosis IP Admission OP Follow up Admissions Clinic Visits Treatment Survivorship • Type of treatment • Social and physical supports • Psychological • Barriers to accessing care

FOCUS OF PT GOALS AND PT PLAN OF CARE ACROSS SETTINGS INTERVENTIONS

Acute Care Rehab Outpatient Early Intervention School Based Therapy • Change in • Acute change Require ongoing EI: 0-3 years old PT impairments Preventative Who functional status in functional skilled PT IU: 3-5 years old which limit access • Change in medical status treatment to school status requiring environment or • New diagnosis intensive PT activities • Prolonged with daily admission progress

Restorative Supportive Where Bedside Rehab gym Outpatient gym Home or daycare School Frequency Variable: 1-7x/week Daily 1-3x/week Variable: 1-7x/week 1-3x/week

Goals • Safety for home • Safety for • School re-entry • Developmental • Normalizing • Return to functional home • Return to skill peer baseline • Return to recreational acquisition interactions • Minimize skill functional activities • Family • Optimizing Palliative regression baseline • Compensatory education navigation of • Prevention of co- • Compensatory strategies school morbidities strategies • Quality of environment • DME movement • Optimizing • Family training • DME/bracing activity and participation limitations

SURVIVORSHIP

• Maximizing outcomes while minimizing long term side effects and the impact on growth • Promoting health and wellness • Improving quality of life • Improving access to ongoing medical care, SURVIVORSHIP support, and surveillance for late effects • Support for patients and families • Screening of educational and vocational progress

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REHABILITATION NEEDS OF SURVIVORSHIP SURVIVORS

• Pain • Fatigue Prevention • Impaired mobility Decrease • Decreased range of motion long term • Decreased strength health • Impaired activities of daily living risks • Cognitive impairments • Neuropathy/nerve disorders Early Identification • Low back pain • General musculoskeletal symptoms

THANK YOU

CASE STUDIES Pediatric Cancers

QUESTIONS REFERENCES

• American Cancer Society. Cancer Facts & Figures 2018. Atlanta: American Cancer Society; 2018. • Barawid E, et al. The Benefits of Rehabilitation for Palliative Care Patients. American Journal of Hospice & Palliative Medicine 2015;32(1):34-43. • Braam KI, et al. Physical exercise training interventions for children and young adults during and after treatment for childhood cancer (Review). Cochrane Database of Systematic Reviews 2013, Issue 4. Art. No.: CD008796.b • Geiger R, et al. Six-Minute Walk Test in Children and Adolescents. Journal of Pediatrics. 2007 Apr;150(4):395-9, 399.e1-2. • San Juan AF, Wolin K, Lucía A. Physical activity and pediatric cancer survivorship. Recent Results Cancer Res 2011;186:319–47. • Silver J, et al. Impairment-Driven Cancer Rehabilitation: An Essential Component of Quality Care and Survivorship. CA Cancer J Clin 2013;63:295-317. • Smolik S, et al. Assessment Tools for Peripheral Neuropathy in Pediatric Oncology: A Systematic Review From the Children’s Oncology Group. Journal of Pediatric Oncology Nursing. 2018, Vol. 35(4) 267–275 • Tseng-Tien Huang and Kirsten K. Ness. Exercise Interventions in Children with Cancer: A Review. International Journal of Pediatrics Volume 2011, Article ID 461512.

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REFERENCES: WEBSITES DEVELOPMENTAL

• American Cancer Society. Cancer A-Z. https://www.cancer.org/cancer.html. Accessed APPENDIX December 2018. • NIH National Cancer Institute. Cancer Types. https://www.cancer.gov/types. Accessed December 2018. • Kids Health from Nemours. Steroids for Treating Cancer. https://kidshealth.org/en/parents/steroid-treatment.html. Accessed December 2018. • Children’s Cancer and Leukemia Group. Introduction to Steroids. https://www.cclg.org.uk/CSOIR/Introduction-to-steroids. Accessed December 2018 • American Society of Clinical Oncology. https://www.cancer.net/. Accessed December 2018. • National Center for Biotechnology Information. https://www.ncbi.nlm.nih.gov/books/NBK459232/. Accessed December 2018 • Children’s Hospital of Philadelphia. The Cancer Center. https://www.chop.edu/centers- programs/cancer-center/conditions. Accessed December 2018. • Association of Pediatric Hematology/Oncology Nurses. http://aphon.org/. Accessed December 2018 • Guide to Physical Therapist Practice 3.0. Alexandria, VA: American Physical Therapy Association; 2014. Available at: http://guidetoptpractice.apta.org/. Accessed December 2018

INFANT POSTURE INFANT POSTURE

• 1 month: • 3 months: beginning physiological flexion, of symmetry, fully rounded back, antigravity flexor flexed neck control emerges, midline orientation of head emerges

LOWER EXTREMITY POSTURAL INFANT POSTURE DEVELOPMENT

• 4 months: strong symmetry, bilateral control of extensor and flexor muscles, emergence of controlled purposeful movement

Knee. Musculoskeletal Key website https://musculoskeletalkey.com/knee-4/. June 7, 2016. Accessed November 1, 2018.

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PROTECTIVE EXTENSION REACTIONS PRIMITIVE INFANT REFLEXES IN SITTING Reflex Onset Integration Stimulus Response Forward 6-7 months Persists Displace Lower center of extremities gravity outside and UE’s base of extend and support abduct to forward protect and support body

Lateral 7 months Persists Same as above Same as above except displacing laterally

Backwards 9-10 months Persists Same as above Same as above except displacing Retained primitive reflexes as a sign of brain imbalance. Brain Balance Centers website https://blog.brainbalancecenters.com/2014/09/retained-primitive- backwards reflexes-sign-brain-imbalance. Access November 1, 2018.

STAGES OF LOCOMOTOR EQUILIBRIUM REACTIONS DEVELOPMENT Reflex Onset Integration Stimulus Response • Early stepping Prone 6 months Persists Tilt supporting Abduction and surface to displace extension or • Rolling center of gravity extremities, with curvature of trunk • Crawling Sitting 7-8 months Persists Same as above Trunk extension or • Creeping flexion to A/P displacement, • Cruising abduction and extension of • Erect ambulation extremities to lateral • Running displacement with trunk rotation • Galloping Quadruped 9-12 months Persists Same as above Similar to prone • Hopping Standing 12-21 months Persists Same as above Ankle • Skipping dorsiflexion/planta rflexion, hip flexion or extension, trunk flexion or extension

KEY GROSS MOTOR SKILLS DEVELOPMENT OF GAIT

• 9-15 months: 3.5 months Rolls prone > supine • Wide base of support 6.5 months Sits independently Rolls supine > prone • Hips abducted, flexed and externally rotated • Tibia in mild internal torsion and varus 9.5 months Creeps, cruises • Elevated center of mass 12 months. Walks 2-3 steps Stands alone well • Increased hip and knee flexion • Full foot initial contact 13.5 months Creeps up stairs • Short stride, increased cadence 22 months Runs Walks upstairs holding rail 28 months Jumps with both feet 4 years old Skipping, galloping

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DEVELOPMENT OF GAIT DEVELOPMENT OF GAIT

• 18-24 months: • 3 to 3.5 years: • Limb is straight at 18 months of age • Mature patterns • Decrease in base of support • Tibiofemoral angle-valgus alignment • Prolonged stance phase • Decreasing femoral antetorsion of the hip • Increased cadence • Center of mass closer to extremities • Center of mass descends to proximal end of legs • Consistent heel strike with knee flexion • Heel strike develops

DEVELOPMENT OF GAIT DEVELOPMENT OF RUNNING

• 6 to 7 years: • 18 months – early running, modified walking, • Fully mature gait pattern limited range of motion, short stride length • Tibiofemoral angle returns to neutral • 2-3 years – smoother stride and run • Femoral antetorsion is resolved • 4-5 years – improvement in power and form • Heel position is neutral • Center of mass at level of third lumbar vertebrae • 5-6 years – advance to level of adult pattern • 6 years – refined adult running pattern

DEVELOPMENT OF STAIR DEVELOPMENT OF JUMPING NEGOTIATION

• 18-24 months: Places two feet on each with • 24 months – jump down from 12 inches handrail • 28 months – jump off floor both feet • 2-3 years of age: 2 feet on each step without • 31 months – jump down 18 inches 1 foot leading support; 1 foot on each step with handrail • 32-33 months – jump down 12 inches both feet • 3-4 years of age: walks up and down steps with 1 foot on each step without support • 37 months – jump down 14-18 inches both feet • 37 months – jump forward 4-14 inches • 38 months – hop on 2 feet 1-3 times • 43 months – hop on 1 foot 1-3 times

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PEDIATRIC STANDARDIZED OUTCOME PEDIATRIC STANDARDIZED OUTCOME MEASURES MEASURES

Test Age Domains Tested Test Age Domains Tested

Pediatric Balance Scale 2.5 to 7 years * Balance Alberta Infant Motor Scale 0 to 18 months Gross motor skills (AIMS) Balance Error Scoring System 5 to 14 years Balance (BESS) Peabody Developmental Newborn to 6 years 11 Gross motor skills Wee Functional Independence 6 months to 7 years * Self care Motor Scales 2 (PDMS-2) months Fine motor skills Measure (Wee FIM) Mobility Visual motor skills Cognition Bayley Scales of Infant 1 month to 3.5 years Gross motor skills Pediatric modified total 5 to 18 years Peripheral Development Fine motor skills neuropathy scale (Ped-mTNS) Neuropathy Cognition Language 6 Minute Walk Test 3 to 18 years Cardiopulmonary Bruininks –Oseretsky Test of 4 to 21 years Fine motor skills PedsQL 2 to 18 years Quality of life Motor Proficiency (BOT-2) Coordination Balance Strength * Can be used above age range if child is expected to be delayed in these areas. Ceiling effect present at upper end of age range

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