PAEDIATRIC SOLID TUMOURS

Alan DavidsonHaematology - Oncology

Red Cross Children’s Hospital

23.22.13.74.655.37.18.68.7

11.332.4

34.6

• US figures show total of 146 cancers per million children aged 0-14 per year

ALL

BRAIN TUMOURS

NEUROBLASTOMA

NHL

WILMS TUMOUR

AML

HODGKIN’S DISEASE

RHABDOMYOSARCOMA

RETINOBLASTOMA

OSTEOSARCOMA

EWING’S TUMOUR

OTHERS

CANCER IN CHILDHOOD

CHILDHOOD CANCER AT RCCH

• Approximately 130 new cases per year

• Many present with advanced disease

• Many have presented to the health service several times over the preceding weeks or months !

• These delays make treatment more difficult … and adversely effects prognosis.

1 6

0

5

4

3

5

4

5

9

8

1 1

1 6

1 7

1 6

4

2

1

6

3

6

5

5

1 6

1 3

1 4

1 7

1 0

3

1

4

3

7

6

7

7

8

1 2

1 5

1 5

Numbers represent actual number of tumours for 2003 / 2004 / 2005

ALL

BRAIN TUMOURS

NHL

AML

WILMS TUMOUR

NEUROBLASTOMA

RHABDOMYOSARCOMA

GERM CELL TUMOUR

HODGKIN’S DISEASE

HEPATOBLASTOMA

BONE TUMOURS

RETINOBLASTOMA

OTHER

SPECTRUM AT RCCH

ONCOLOGY FOR THE PAEDIATRICAN:

What’s the central message ?

• EARLY DIAGNOSIS• MEANS …

– Improved prognosis– Less treatment related morbidity

• NEEDS …– Working knowledge of common

tumours– High index of suspicion

IMPROVED PROGNOSIS“WHAT A DIFFERENCE A DAY (OR TWO) MAKES”

0 50 100 150 200 250 300 350

T ime - months

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Cum

ulative Proportion S

urviving

S tage I 94.4% S tage II 96.2% S tage III 84.9% S tage IV 54.2%

Comple te CensoredCh i-squa re = 22 .898 d f = 3 p = 0 .00004

FAVOURABLE HISTOLOGY WILMS’ TUMOUR

O ver all 5 -year S ur vi valLM B Chemother apy

1988-2004[Log R ank p value 0 .0 6 ]

Complete Cens ored

Stage II and III [88.2% ]

Stage IV [66.0% ]

0 20 40 60 80 100 120 140 160 180 200 220

Time - months

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Cum

ulative Proportion S

urviving

BURKITT’S LYMPHOMA

EWING’S SARCOMA

WILMS’ TUMOUR TREATMENT…

– Surgery (primary or delayed) for all

– Chemotherapy• Stage I or II: Vincristine + Dactinomycin• Stage III or IV: Add DOXORUBICIN

– RENAL BED RADIOTHERAPY for local Stage III– PULMONARY RADIOTHERAPY for lung metastases

LESS TOXICITY“SMALLER OMELETTE … LESS EGGS”

• LEUKAEMIAS– ALL / AML / CML

CLASSIFYING CHILDHOOD MALIGNANCY

• BRAIN TUMOURS– Seperate textbook !

• RARE TUMOURS– Thyroid Ca / Melanoma

• EMBRYONAL TUMOURS– Neuroblastoma– Nephroblastoma– Rhabdomyosarcoma– Hepatoblastoma– Retinoblastoma– PNET– Germ Cell Tumour

• BONE TUMOURS– Osteogenic Sarcoma– Ewing’s Sarcoma

• Named for MAX WILMS• Derived from the metanephros = hence the classic

triphasic nature = epithelial / blastemal / stromal

• Associations– Overgrowth = BWS / Hemihypertrophy– Non-overgrowth = Aniridia / WAGR / Denys-Drash

• Age 0-5yrs (median 3yrs)

• Presents with Mass / Pain / Haematuria / Paraneoplasias

• Renal mass … L>R (not across midline) 10% bilateral

• Metastasis … lungs / liver / brain / (bone)

NEPHROBLASTOMA

• Stage I ... confined to kidney

• Stage II ... through capsule

• Stage III ... residual tumour» Local spread» Nodes» IVC Thrombus

• Stage IV ... metastatic disease

• Stage V ... bilateral disease

WILMS’ TUMOUR

STAGING

• DIAGNOSIS and STAGING– FBC / Urea & Creatinine / LDH– Urine– Ultrasound and CT Abdomen– CXR and CT Chest– Biopsy if deemed inoperable or protocol calls for pre-op

chemo

• MANAGEMENT– Two schools (NWTS and SIOP)– Surgery + Chemo +/- XRT– Same results ! In fact …

DIAGNOSIS AND MANAGEMENT

So good that we’re deintensifying treatment !!

0 50 100 150 200 250 300 350

T ime - months

0.0

0.1

0.2

0.3

0.4

0.5

0.6

0.7

0.8

0.9

1.0

Cum

ulative Proportion S

urviving

S tage I 94.4% S tage II 96.2% S tage III 84.9% S tage IV 54.2%

Comple te CensoredCh i-squa re = 22 .898 d f = 3 p = 0 .00004

FAVOURABLE HISTOLOGY WILMS’ TUMOUR

• Derived from primitive neural crest cells of the sympathetic nervous system– Hence they are found along the sympathetic chain– 1/3 adrenal 1/3 abdominopelvic 1/3 thoracic or cervical

• Age 0-3yrs [median of 17m] [40% are infants]– Prognosis inversely related to age … Younger kids usually have

lower grade tumours (some of which regress spontaneously) in more favourable sites (cervicothoracic) and are much less likely to metastasize

• Staging:– I: confined to organ– II: extends outside organ (+/- nodes) NOT across midline– III: across midline … involving contralateral nodes– IV: Metastasis to Liver / Bone and BM / Skin– IVS: I/II with remote disease in liver, skin, bone marrow (<10%)

NEUROBLASTOMA

• Abdominal mass > 50% … usually smooth and hard (crosses midline)

• Pelvic Mass• Mediastinal or cervical mass

• Mass effect … proptosis / superior mediastinal syndrome / UAO / spinal cord compression

• Bone marrow … anaemia / thrombocytopaenia / bone pain with limp

• Metabolic (catecholamines and vasoactive intestinal peptides) … sweating / diarrhoea & vomiting /

hypertension• Bluish skin marks (typically blanch)• Opsoclonus-myoclonus / Cerebellar ataxia

CLINICAL PRESENTATION

• DIAGNOSIS and STAGING– FBC / Urea & Creatinine / LDH– Urinary catecholamines (HVAs and VMAs)– Calcified mass on plain AXR– Imaging of abdomen, chest and possibly spine– Bone Marrow / MIBG / Bone Scan

– Biopsy can be avoided if BM involved !

• MANAGEMENT– Surgery +/- Chemotherapy

DIAGNOSIS AND MANAGEMENT

• Commonest soft tissue sarcoma of childhood• Derived from primitive muscle

• Age 2-15yrs• Prognosis varies with

– Histology: Embryonal > Alveolar– Site: Orbit > Paratesticular > Vaginal > Bladder / Prostate >

Retroperitoneal > Extremity > Parameningeal– Stage

• Staging:– I to IV based on complex system using TNM and Site– IRS Grouping now generally followed …

Group I completely excised Group II microscopic residua

Group III macroscopic residua Group IV metastases

RHABDOMYOSARCOMA

• DIAGNOSIS and STAGING– FBC / Urea & Creatinine / LDH– Local imaging …

CT for abdomen / MRI for parameningeal tumours

– CXR and CT chest– Bone Marrow

• MANAGEMENT– Chemotherapy with Surgery +/- XRT

DIAGNOSIS AND MANAGEMENT

• Commonest paediatric liver tumour• Age usually under 18 months• Presents as hepatomegaly with elevated FP• Metastasizes locally and to lungs

• DIAGNOSIS– FBC / Renal and liver functions / FP– CT abdmen and chest

• MANAGEMENT– Chemotherapy – Surgery

HEPATOBLASTOMA

CLINICAL SCENARIOS IN SOLID PAEDIATRIC

TUMOURS

AN APPROACH FOR THE GENERAL PAEDIATRICIAN

LEUKAEMIA LYMPHOMA or NEUROBLASTOMA

• ASK ABOUT …– bone pain

• WATCH OUT FOR …– swollen gums– lymph nodes– abdominal masses– proptosis

1. PANCYTOPAENIA

MUST exclude HIV infection …

LEUKAEMIA (or LYMPHOMA)– FBC: Hb Plt WCC / … look for blasts– Chemistry: LDH (with a normal ALT) and Urate – CXR: mediastinal mass in T-cell lymphoma

NEUROBLASTOMA– Look for an Abdominal Mass !– FBC: typically anaemic with preserved platelets– Chemistry: LDH (with a normal ALT) and urinary

HVAs– Xrays: lytic bone lesions or calcified abdominal mass

1. PANCYTOPAENIA

WHO SHOULD DO THE BONE MARROW ?

Generally the receiving hospital but this matter should always be discussed!

LEUKAEMIA (or ANY SUSPECTED MALIGNANCY)– Aspirates and trephines Flow cytometry

Cytogenetics Ig gene rearrangements by PCR FISH for translocations

– Complicated set of investigations: leave for referral centre !

OTHER INDICATIONS– Disseminated TB / ITP / Storage disorders.– Probably fine to do.

1. PANCYTOPAENIA

2. BONE PAIN

• NOT localised

• Wakes the child

• Limp or Reluctance to bear weight

• A toddler who stops walking

• Backache!!

2. BONE PAIN

• Again, malignancies involving the bone marrow…

LEUKAEMIA or LYMPHOMA NEUROBLASTOMA

• Remember … if local pain and swelling (especially around the knee joint)…

BONE TUMOURS eg. OSTEOGENIC SARCOMA

• from 6m to 6y …

ABDOMINAL MASSis a tumour until

proven otherwise

ALWAYS CONSIDER SEDATING THE PATIENT IF YOU CAN”T PALPATE THE ABDOMEN !

3. ABDOMINAL MASS

WILMS TUMOUR• flank mass / typical imaging / LDH

HEPATOBLASTOMA• hepatomegaly / typical imaging / Feto-protein

NEUROBLASTOMA• adrenal mass / typical imaging / LDH and HVAs• ? signs of metastatic involvement

BURKITT LYMPHOMA• central abdominal mass / nodes on imaging / LDH

3. ABDOMINAL MASS

No need for

BIOPSY !!

REFER

GERM CELL TUMOUR Feto-protein

BURKITT LYMPHOMA LDH and urate

RHABDOMYOSARCOMA LDH

NEUROBLASTOMA LDH

(3. PELVIC MASS)

No need for

BIOPSY !!

REFER

4. AN UNEXPLAINED MASS

• SITES– Head and Neck– Limbs– Testis

5. UNEXPLAINED NEUROLOGY• Headache > 2 weeks• Early morning vomiting• Ataxia / unsteady gait• Cranial Nerve Palsy

BRAIN TUMOURS (watch out for neurocutaneous syndromes)

• Posterior fossa … ataxia and cranial nerve palsies• Supratentorial … headache and vomiting hemiplegia

RHABDOMYOSARCOMA (often occult in the sinuses)

• Lower cranial nerve palsies eg. VI, VII, IX, XII

NEUROBLASTOMA (secondary to skull infiltration)

• Commonly VI nerve palsy

7. EYE CHANGES

• White Reflex• Recent Onset Squint• Loss of Vision

RETINOBLASTOMA

• Proptosis

LEUKAEMIA especially Acute Myeloid Leukaemia NEUROBLASTOMA RHABDOMYOSARCOMA

7. EYE CHANGES• Leukocoria

• REFER to an Ophthalmologist urgently for slit lamp examination

7. EYE CHANGES• Proptosis

• CONSIDER Leukaemia / Neuroblastoma / Rhabdomyosarcoma … abnormal FBC means diagnosis might be made on BM examination … REFER

• OTHERWISE REFER to an Ophthalmologist for urgent biopsy

• Pallor plus Bleeding• Persistent Fever / Apathy / Weight Loss• Bone Pain• Adenopathy• Unexplained Neurological Signs• Unexplained Mass• Eye Changes

IN SUMMARY … REMEMBER THE WARNING SIGNS

THE BOTTOM LINE

• Be aware of the clinical spectrum of childhood cancer

• Don’t waste time with special investigations … Seek expert advice

• Refer cases early … and URGENTLY !