NCG GUIDELINES 2020

PAEDIATRIC HEMATOLYMPHOID AND SOLID TUMOURS

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Table of Contents

PEDIATRIC HEMATOLYMPHOID TUMORS .......................................................................................................... 4

PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA ................................................................................................... 5
Treatment Algorithm: Newly diagnosed ALL ................................................................................................... 5
Risk Stratification ............................................................................................................................................. 6
PEDIATRIC ACUTE MYELOID LEUKEMIA ............................................................................................................... 7
Treatment Algorithm: Newly diagnosed AML ................................................................................................. 8
PEDIATRIC ACUTE PROMYELOCYTIC LEUKEMIA (APML)...................................................................................... 9
Treatment Algorithm: Newly diagnosed APML (start from AML pathway) .................................................... 9
PEDIATRIC CHRONIC MYELOID LEUKEMIA......................................................................................................... 10
Treatment Algorithm: Pediatric CML ............................................................................................................. 10
Risk Stratification
11
Monitoring and response guidelines in CML CP ............................................................................................ 11
LANGERHANS CELL HISTIOCYTOSIS.................................................................................................................... 12
Treatment Algorithm: `Newly diagnosed case of Langerhans cell Histiocytosis ........................................... 12
NON-HODGKIN LYMPHOMA (NHL) .................................................................................................................... 14
Treatment Algorithm: Newly diagnosed Non-Hodgkin lymphoma ............................................................... 14
Alternate Regimen option: BFM Classification and treatment ...................................................................... 15
Diagnostic workup for Suspected NHL........................................................................................................... 16
PEDIATRIC HODGKIN LYMPHOMA ..................................................................................................................... 17
Treatment algorithm: Pediatric Hodgkin Lymphoma .................................................................................... 17
APPENDIX A (FLOWCYTOMETRY) ....................................................................................................................... 19
A. Acute Leukemia- Essential panel (a) .......................................................................................................... 19
B. Acute leukemia – Optimal panel (b) .......................................................................................................... 19
C. Acute leukemia – Optional panel (c).......................................................................................................... 20
D. DNA ploidy by flow cytometry for B-ALL – Optimal (b) ............................................................................. 20
E. B-ALL Minimal Residual Disease Panel Essential (a) + Optional (c) ........................................................... 20
F. T-ALL MRD Optimal (b) + Optional (c) ....................................................................................................... 21
G. AML MRD Optimal (b) + Optional (c)......................................................................................................... 21
H. Lymphoproliferative disorders/Lymphoma Essential (a) + Optimal (b) + Optional (c) ............................. 21
APPENDIX B ........................................................................................................................................................ 22
Histopathology for lymphomas ..................................................................................................................... 22
Lymphoma Tissue Diagnosis .......................................................................................................................... 22
A. Hodgkin lymphoma.................................................................................................................................... 22
(cHL) classical Hodgkin Lymphoma and (NLPHL) Nodular Lymphocyte Predominant Hodgkin Lymphoma-
requisites for diagnosis .................................................................................................................................. 22

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 5. CD3 and CD20 negative NHL- requisites for diagnosis .............................................................................. 24
APPENDIX C ........................................................................................................................................................ 25
Response assessment for Lymphomas .......................................................................................................... 25
PEDIATRIC SOLID TUMORS ............................................................................................................................... 26
WILMS TUMOUR ................................................................................................................................................ 27
Treatment Algorithm: Wilms Tumor.............................................................................................................. 27
Risk Stratification ........................................................................................................................................... 28
Staging of Wilms Tumour............................................................................................................................... 28
RT guidelines in Wilms Tumour ..................................................................................................................... 29
NEUROBLASTOMA ............................................................................................................................................. 30
Treatment Algorithm: Neuroblastoma .......................................................................................................... 30
Risk Stratification ........................................................................................................................................... 31
Very low Risk ..................................................................................................................................................... 31
Infant (<18 months) asymptomatic, no high-risk molecular features, Ganglioneuroma any age..................... 31
Low Risk ............................................................................................................................................................. 31
Infant (<18 months) NB L2 or stage II/III (non-metastatic)................................................................................ 31
Intermediate Risk .............................................................................................................................................. 31
Stage M infant (<18 months) NB, Stage II/III, L2 non-infantile NB, infant (<18 months) NB L2 or stage II/III
with 11q aberration ........................................................................................................................................... 31
High Risk ............................................................................................................................................................ 31
Any NMYC amplified tumour, Metastatic Stage M(non-infant), infant NB MS with 11q aberration ................ 31
HEPATOBLASTOMA ............................................................................................................................................ 32
Treatment Algorithm: Hepatoblastoma ........................................................................................................ 32
Risk Stratification ........................................................................................................................................... 33
RETINOBLASTOMA ............................................................................................................................................. 34
Treatment Algorithm: Retinoblastoma .......................................................................................................... 34
Grouping for Intraocular Retinoblastoma...................................................................................................... 34
Treatment Algorithm: Retinoblastoma- Unilateral........................................................................................ 35
Treatment Algorithm: Retinoblastoma- Bilateral .......................................................................................... 36
EXTRACRANIAL GERM CELL TUMOUR ............................................................................................................... 38
Treatment Algorithm: Extra Renal Germ Cell Tumor..................................................................................... 38
Risk stratification ........................................................................................................................................... 39
RHABDOMYOSARCOMA .................................................................................................................................... 41
Treatment Algorithm: Neuroblastoma .......................................................................................................... 41
Radiotherapy Guidelines for Rhabdomyosarcoma ........................................................................................ 42
Risk stratification of RMS ............................................................................................................................... 43
NASOPHARYNGEAL CARCINOMA....................................................................................................................... 44

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 Treatment Algorithm: Nasopharyngeal Carcinoma ....................................................................................... 44
ANNEXURE -1 ..................................................................................................................................................... 45
DIAGNOSTIC INVESTIGATIONS FOR COMMON PAEDIATRIC SOLID TUMOURS .................................................. 45
ANNEXURE 2 ......................................................................................................... Error! Bookmark not defined.
PATHOLOGY SYNOPTIC REPORTING FORMS......................................................... Error! Bookmark not defined.

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 PEDIATRIC HEMATOLYMPHOID TUMORS

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 PEDIATRIC ACUTE LYMPHOBLASTIC LEUKEMIA
Treatment Algorithm: Newly diagnosed ALL

Suspected Acute
Lymphoblastic Leukemia (ALL)

Examination:
CNS, Lymph nodes, Liver, Spleen, Testes

Baseline Blood Investigations: Standard risk*

CBC, peripheral smear, blood group, 3 drug induction (Week 1 – 5) MRD^
Renal Function Test(RFT), Liver Function Consolidation (Week 6 – 8) If MRD> 0.01% at
Test(LFT), Serum electrolyte, LDH Interim maintenance (Week 9 – 17) the end of induction
Coagulation profile(a), Viral markers(b) Delayed intensification (Week 18 – 24) go to High risk arm
Maintenance (Week 1-84) 8 cycles
Chest Radiograph (a) CNS prophylaxis (intrathecal chemo)

Bone marrow/peripheral blood if child

unstable for bone marrow Intermediate risk*
examination) 4 drug induction (Week 1 – 5) MRD^
Morphology, Biopsy, Consolidation (Week 6 – 10) If MRD > 0.01% at
Cytogenetics (a) karyotyping for Interim maintenance (Capizzi MTX) (Week the end of induction
ploidy(a) FISH for t12;21, BCR 11 – 18) go to High risk arm
ABL/t(9;22) KMT2A/MLL 11q23 break Delayed intensification (Week 19 – 25)
apart probe (a) Maintenance (Week 1 – 84) 8 cycles
Other translocations by FISH and CNS prophylaxis (intrathecal chemo)
workup for Ph like ALL (b) If Ph +ve ALL or Ph
Flowcytometry for immunophenotyping like ALL treat on
High risk*
Baseline ALL panel + ploidy + MRD panel High risk arm with
4 drug induction (Week 1 – 5) MRD^
(a) TKI
Consolidation (Week 6 – 14) MRD^
Molecular PCR studies as indicated (b)
Imaging # If CNS 3 on day 8:
Interim maintenance (HDMTX) (Week 15 – 18 Gy (Cranial RT)
Special investigations
22)
CSF studies cell count + cytospin (a) If testicular
Delayed intensification (Week 23 – 29)
USG/testicular biopsy when indicated involvement
Maintenance (Week 1 – 84) 8 cycles
2D-ECHO (b) persists at end of
CNS prophylaxis (intrathecal chemo)
consolidation (24
Gy bilateral
In case of induction failure or persistent testicular radiation)
MRD positivity consider for allogenic bone
marrow transplant in CR1

^ MRD = Minimal residual disease by flow cytometry or PCR to assess response to treatment. Risk stratification depends
upon MRD assessment. To be done at centers with expertise in flowcytometry and/PCR MRD detection. # Imaging like
CXR for patients with T-ALL or LBL with mediastinal mass at the end of consolidation at the end of consolidation to
assess response to treatment.

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 Risk Stratification

Standard Risk Intermediate risk High risk

B lineage ALL and B lineage ALL and T lineage ALL or
Age > 1 and <10 years and Age > 10 years B lineage ALL and
WBC <50,000/mm3 and or Presenting WBC > High risk cytogenetics
Prednisolone good responder and 50,000/mm3 BCR-ABL, iAMP21, MLL rearranged,
No testicular or bulky disease and or testicular/bulky disease and t(17;19), Hypodiploidy (< 45
No high-risk cytogenetics and Prednisolone good response and chromosomes or DNA index <0.81)
MRD <10 -4 at week 5 No high-risk cytogenetics and or Prednisolone poor response
MRD <10 -4 at week 5 or MRD positive (>10-4) at week 5
or No CR at the end of induction
or CNS disease

Protocol options:
• ICICLE-2014
• BFM 90
• BFM 95 (ALL)
• UK ALL protocols
• COG protocols
• MCP 841
• Any others with similar backbone

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PEDIATRIC ACUTE MYELOID LEUKEMIA
Newly diagnosed AML

Suspected Acute Myeloid Leukemia (AML)

Granulocytic sarcoma threatening vision

or spinal cord compression
Examination:
Consider focal radiation (b)
CNS, Lymph nodes, Liver, Spleen, Testes,
Gum hypertrophy, Presence of skin lesions
or granulocytic sarcomas, Performance
status
Child fit for intensive chemotherapy (a)*
Baseline Investigations:
Induction with Anthracycline + Cytarabine+ Etoposide
CBC, peripheral smear, MPO stain, Renal
3+7(DA)/ADE/FLAGIda/DAT
function test (RFT), Serum electrolytes,
Liver function test (LFT), LDH, Blood group
Coagulation profile, (a),
Viral markers(b) Second cycle of chemotherapy with Cytarabine +/-
Anthracycline (a)
Chest Radiograph (a) HiDAC/HDAC/DA /ADE/MAE/LDAC

Bone marrow/peripheral blood if child

unstable for bone marrow examination) In remission by flow or Not in morphologic
Morphology, Biopsy, morphology (a) remission or by
Cytogenetics (a) flowcytometry
Cytogenetics combination of conventional 
karyotyping and FISH (a) Transplant counseling
2 to 3 more cycles of chemo (a)
t(8;21) RUNX1-RUNX1T1 and transplant workup (a)
HiDAC/ MiDAC/Clad AraC
t(16;16) or inv(16) CBCB-MYH11 + maintenance for 12 months (b)
t(15;17) PML-RARA, 11q23 MLL break apart
probe, -5 or del(5q),-7 or del(7q) (a)
Flowcytometry for immunophenotyping 2 to 3 more cycles of
Baseline AML panel (a) + MRD panel (b) chemo (a)
Molecular PCR as indicated (b) HiDAC/MACE/MiDAC/
FLT3-ITD, NPM1 mutation Biallelic mutation Clad AraC
of CEBPA, KIT (b)

Special investigations
CT scan thorax (b) High risk AML
Transplant counselling and Allogeneic
CSF studies cell count + cytospin (a) Hematopoietic stem
USG/testicular biopsy when indicated (b) HLA typing upfront
After 3 to 5 cycles of cell transplantation
2-D ECHO (a)
chemotherapy

* In case patient has active infection or malnourished and child is not fit for intensive chemotherapy, may
consider metronomic chemotherapy for 1 to 3 months
3+7(DA) Daunorubicin + Cyatarabine/AraC HiDAC High dose AraC
DAE Daunorubicin AraC Etoposide LDAC Low dose AraC
FLAG Ida Fludarabine AraC GCSF Idarubicin MAE MItoxantrone AraC Etoposide
Clad AraC Cladarabine AraC

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Treatment Algorithm: Newly diagnosed AML

Newly diagnosed AML (AML-1)

1 Standard risk Based on cytogenetics and M1 marrow t(8;21) RUNX1-RUNX1T1
or MRD (if available) negative at end of t(16;16) or inv(16) CBCB-MYH11
induction II
2 Intermediate risk If not satisfying criteria for high risk or
standard risk
3 High risk Based on cytogenetics and positive MRD Complex karyotype
or >5% blasts on morphology in the -5 or del(5q)
bone marrow at end of Chemotherapy -7
cycle II FLT3 ITD with allelic ratio > 0.4

Protocol options

UK MRC series of protocols including Myechild-1 protocol

St Jude AML 08
BFM AML protocol
Any Anthracycline and Cytarabine based protocol

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PEDIATRIC ACUTE PROMYELOCYTIC LEUKEMIA (APML)

Treatment Algorithm: Newly diagnosed APML (start from AML pathway)

CBC, peripheral smear, coagulation profile including
APML suspected on peripheral PT/PTT/INR, D-Dimer, Fibrinogen, 68-12 hourly as
smear or presentation (DIC) required.
suggestive of APML
Platelet transfusion/Fresh frozen plasma as required

Diagnosis by FISH for PML-RARA (a)

Start Arsenic or All Trans Retinoic Molecular studies by t(15;17) for FLT-3 (b)
Acid (ATRA) even if diagnosis is
not confirmed
Induction

WBC <10,000 arsenic and

ATRA based regimen
Consolidation
+anthracycline induction
Arsenic + ATRA based consolidation
for min of 42 days upto 60
followed by FISH (a) or RQ-PCR (b)
days until remission
Refer to center with expertise in Repeat total of 3 to 4 cycles
management of Leukemia
Induction Consolidation
Arsenic + ATRA +anthracycline
WBC >10,000 arsenic and
based consolidation followed by
ATRA + anthracycline
FISH(a) or RQ-PCR (b)
based regimen + for min
Repeat total of 4 cycles followed
of 42 days upto 60 days
by maintenance
until remission

Repeat total of 3 to 4 cycles

Supportive care

1. Platelet transfusion to keep platelets >30,000/cumm until coagulation parameters

are stable
2. FFP/Cryoprecipitate for Hyperfibrinolysis to keep Fibrinogen >150 mg/dL
3. Hydroxyurea/Anthracyclines for WBC >10,000 or rising counts
4. Steroids Dexamethasone for Differentiation syndrome (DS) 10mg/m2 in 2 divided
doses
5. Hold Arsenic and ATRA for severe DS only

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PEDIATRIC CHRONIC MYELOID LEUKEMIA

Treatment Algorithm: Pediatric CML

Chronic Myeloid Leukemia

Imatinib(a)
Chronic Phase or
Investigations (baseline) Dasatinib (b)

Complete blood Counts

Peripheral Smear Imatinib or Dasatinib
Renal function test (RFT) Accelerated phase Recommend transplant in CR
Liver function test (LFT)
LAP score
Bone marrow aspirate and
biopsy. Acute leukemia like treatment
Morphology with Imatinib or Dasatinib
Cytogenetics (FISH) Recommend transplant in CR
RT/RQ-PCR Blast Phase If transplant not an option,
consider oral maintenance
chemotherapy with
6TG,Etoposide with Imatinib or
Dasatinib

CML Chronic Phase with

treatment failure or Change to 2nd generation TKI
development of TKI
Recommend transplant
resistant mutation

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 Risk Stratification

Bone marrow blasts <10%

Chronic Phase
Does not meet criteria for AP or BC

Blasts 10 -19% of WBC count or BM

cells

>20% basophils in peripheral blood

Persistent thrombocytopenia (<100)

unrelated to therapy; persistent
thrombocytosis (>1000) unresponsive
Chronic Myeloid Leukemia Accelerated phase to therapy

Increasing spleen, or WBC count or

high platelets unresponsive to therapy

Cytogenetic evidence of clonal

evolution (second Ph, trisomy 8,
isochromosome 17q, trisomy 19),
complex

Blasts >20% of WBC count or BM

cellsExtramedullary blast proliferation
Blast Phase
Large foci/cluster of blasts in bone
marrow biopsy

Monitoring and response guidelines in CML CP

Time (months) Failure Warning Optimal Response
{Investigation}
0 {FISH+ RTPCR} NA High risk; Additional NA
(a) cytogenetic
abnormalities
3 {FISH} (a) No HR; stable disease or NA CHR
disease progression PCyR; Ph+ <35%
BCR-ABL< 10 % IS
6 {FISH} (a) Less than CHR; NA CCyR; Ph+ 0%
no CyR: Ph+ >95% BCR-ABL< 1 % IS
12 {RQPCR} (a) Less than PCyR: Ph+ >35% Less than MMR MMR BCR-ABL <0.1% IS
18 {RQPCR} (a) Less than CCyR NA MMR or better
After 18 months Loss of CHR; loss of CCyR; Loss of MMR; TKI
{RQPCR} (a) TKI resistant mutation resistant mutation

FISH Fluorescent in-situ hybridization

RQ-PCR Real-time Quantitative PCR
CHR Complete Hematological response
PCyR Partial Cytogenetic response
CCyR Complete cytogenetic response
MMR Major molecular response

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 LANGERHANS CELL HISTIOCYTOSIS
Treatment Algorithm: `Newly diagnosed case of Langerhans cell Histiocytosis

Examination Group 1 (RO+)

Skin and scalp rashes, purpura, Multisystem LCH with
bleeding, jaundice, pallor, ear risk organ involvement Adequate
discharge, gum and palatal lesions, like liver spleen lung response
soft tissue swellings and hematological
lymphadenopathy, dyspnea, 6 weeks Continuation
tachypnea, intercostal retractions, induction +
liver, spleen, neurological Maintenance
examination Prednisolone
Group 2 (RO -) + Vinblastine
Investigations Multisystem Low risk + Etoposide
CBC, ESR, Renal function test, liver Multi system LCH
without risk organ Inadequate
function test, coagulation studies,
involvement response
skeletal survey(a), response
Urine specific
Response gravity if CNS risk (b)
assessment assessment
Reinduction
PET scan (b)
NAD = Noif active disease +
MRI brain CNS involvement
Continuation
suspected
NED = No(b) especially
evidence with
of disease Group 3 +
history of polyuria and endocrine
Single system low risk Maintenance
workup (b)
High resolution CT for suspected Single system involved
lung involvement (b)
GI biopsy if patient has diarrhea (b) Curettage/Intra lesional steroids
Biopsy from involved site and stain Single bone lesion Or Low dose radiation
for CD1a and Langerin (CD207) (a) Observation
Bone marrow biopsy for multi
system disease (a)

AD better = Active disease better with reduction In size of lesion or SUV uptake on PET/Based on CT/Xray
AD worse = Active disease worse
RO+ Risk organ involved
RO- No involvement of Risk Organs

Chemotherapy options for salvage (recurrent or refractory LCH)

• Cladribine/Cytarabine
• Lenalidomide and Dexamethasone
• Vincristine/Cytarabine
• BRAF inhibitors (for BRAF V600E positive refractory or recurrent LCH)

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 Induction Reassessment PET Post induction Maintenance Total duration
Treatment (3month/cycle) of treatment
(Vinblastine+

Prednisolone)

Group 1 High Risk NAD/NED # Continuation 6 cycles of 24 months

(+Etoposide) (+Etoposide) maintenance
(in good
AD Better/Intermediate Reinduction> (Etoposide in first responders)
Continuation 2 cycles)

AD Worse Salvage

Group 2 Low Risk NAD/NED Continuation 3 cycles of 15 months

(-Etoposide) maintenance
AD Better/Intermediate Reinduction> (in good
Continuation (Etoposide) responders)

AD Worse Salvage

Group 3 Low Risk NAD/NED Continuation None 6 months

(-Etoposide)
AD Better/Intermediate Reinduction> Stop treatment (in good
Continuation after Week 25 responders)
(End of
AD Worse Salvage continuation)

# AD Active disease
NAD No active disease
NED No evidence of disease

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 NON-HODGKIN LYMPHOMA (NHL)
Treatment Algorithm: Newly diagnosed Non-Hodgkin lymphoma

Group A 2 cycles of chemotherapy on

FAB/LMB 96
Stage I completely resected or
Or
abdominal stage II
MCP-842 (4 to 6 cycles)

Burkitt lymphoma/Diffuse
Large B-Cell Lymphoma (I)

FAB-LMB Classification Group B

Induction + consolidation +
Pre phase COP (7 days) maintenance phase as per
Multiple extra-abdominal sites
FAB/LMB 96/COG C5961
Imaging to assess response Non resected stage I, II and III
Or MCP 842
to treatment. Imaging same Stage III with <25% Bone marrow
Or COG ANHL 131
as baseline (a) involvement and no CNS involvement
+ Rituximab *
Induction + consolidation
Repeat Imaging (a)

In case of residual disease

Repeat biopsy (a)

If adequate response /biopsy Group C

negative complete
chemotherapy Stage IV disease with or without CNS Induction + consolidation +
involvement maintenance phase as per
Patients with poor response to initial FAB/LMB/COG ANHL 1131
prophase COP protocols
Patients presenting after more than 1 Or MCP 842 protocol 8 cycles
month after primary surgery or + Rituximab *
recurrence post-surgery also need to
be treated on high risk protocol

* + Rituximab can be given in following cases (b)

• Group B with Bone marrow involvement / Group C / inadequate initial response

• R2 disease Stage II stage IV as in the BFM classification below

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 Alternate Regimen option: BFM Classification and treatment

R1 Completely resected Stage I Chemotherapy as per

and II GER-GPOH-NHL-BFM 95
R2 Non resected stage I,II, and III + Rituximab * for R2 disease
(with LDH <500IU/L)
Burkitt lymphoma/Diffuse
Large B-Cell Lymphoma (II)
BFM Classification Stage III with LDH 500-999 IU/L
Stage IV, BMA blasts >25%, no Chemotherapy as per
CNS disease and LDH < 1000 IU/L GER-GPOH-NHL-BFM 95
Stage III, IV with BMA blasts > + Rituximab *
25%, with LDH >1000 IU/L
Any CNS disease

Biopsy of mass: Treatment is as per leukemia

(Nodal/extra-nodal protocol for Pre B ALL
B-LBL
lesion) Histopathology
BFM 90 or ICICLE or institutional
and
protocol for Pre B ALL are
Immunohistochemistry(a)
recommended

Lymphoblastic lymphoma

Biopsyof mass:
(Nodal/extra-nodal
Treated as per leukemia protocol
lesion) Histopathology
for T ALL BFM 90 or ICICLE
T-LBL and
protocol or institutional protocol
Immunohistochemistry
for T ALL are recommended
Pleural fluid for
flowcytometry( if Pleural
effusion present)
Primary Mediastinal B cell lymphoma(PMBCL) specific type of B cell lymphoma treated on DA-REPOCH
(Dose adjusted R EPOCH) 6 cycles (a) Reassessment scan is done only after the 6 cycle of chemotherapy

ALCL 99 protocol (3 cycles)

Or
MCP-842 with Vinblastine (8 cycles)
Low Risk Or
Stage I & II NHL- BFM protocol (R1/R2)
Anaplastic large cell (no visceral/skin/mediastinal
Or
disease)
lymphoma (ALCL) COG ANHL 12P1 backbone

* (Risk groups vary

between protocols) ALCL 99 protocol (6 cycles- both
High risk Standard risk and High risk)
Stage III & IV Or
(OR visceral/skin/mediastinal
MCP-842 with Vinblastine
disease- irrespective of stage)
(8 cycles with 12 months maintenance)
Or
NHL- BFM protocol (R3/R4)
Or
COGANHL 12P1 backbone

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ALCL relapse is salvageable with Vinblastine based chemotherapy (b)

Diagnostic workup for Suspected NHL

1 History and Symptomatic large mediastinal masses, epidural or paraspinal tumors, should be
physical recognized on examination and dealt with as an emergency. Steroids can be initiated
exam before diagnostic confirmation but biopsy should not be delayed.
2 Laboratory Baseline labs CBC, Renal function test, Liver function test, serum electrolytes LDH
Coagulation profile, (a) Viral Markers(b)
Bone marrow aspirate and biopsy (a)
CSF cytospin and morphology (a)
3 Imaging CXR (a) For initial staging of tumor and response assessment
CT scan neck chest abdomen (Treatment modality is based on site of lesion and
and pelvis (a) best suited modality at that particular center on a
OR case by case basis)
PET scan whole body (b)
Ultrasound for certain intra-
abdominal masses (b)
2 D ECHO (a)
4 Histology Biopsy (a) NHL is a heterogenous group of disorders. Common
Excision biopsy or core biopsy Pediatric NHLs include
Histopathology(a) • Aggressive mature B cell NHLs
Immunohistochemistry (a) as (Burkitt lymphoma and
in appendix Diffuse large B cell lymphoma)
• Lymphoblastic lymphoma T/B cell type
Flowcytometry on pleural
• Primary mediastinal large B cell lymphoma
effusion or ascitic fluid where
(PMBCL)
possible (b)
• Anaplastic large cell lymphoma (ALCL)
Miscellaneous NHL
5 Molecular Burkitt lymphoma t(8;14)(q24;q32) t(2;8) or t(8;22)(b)
studies (b) Anaplastic large cell lymphoma t(2;5)(p23;q35)(b)

Staging (Due to high incidence of extra-nodal disease Murphy’s staging is used for NHL)
Burkitt’s and DLBCL are stratified as mentioned subsequently.
Stage I Involvement of a single tumor or nodal area excluding the abdomen and mediastinum
Stage II Disease extent is limited to a single tumor with regional node involvement, two or more
tumors or nodal areas involved on one side of the diaphragm, or a primary gastrointestinal
tract tumor (completely resected) with or without regional node involvement.
Stage III Tumors or involved lymph node areas occur on both sides of the diaphragm. Stage III NHL
also includes any primary intrathoracic (mediastinal, pleural, or thymic) disease, extensive
primary intra-abdominal disease, or any paraspinal or epidural tumors.
Stage IV In stage IV childhood NHL, tumors involve the bone marrow and/or CNS, regardless of other
sites of involvement.
• Bone marrow involvement is defined as 5% or more malignant cells the bone marrow, with
normal peripheral blood counts and smears.
• Patients with lymphoblastic lymphoma with more than 25% malignant cells in the bone marrow
are considered to have Acute Lymphoblastic Leukaemia and to be treated on ALL protocols.
• Patients with Burkitt’s lymphoma with >25% blasts are considered as Burkitt’sleukaemia but
treated on Burkitt’s lymphoma protocol as stage IV disease with higher intensity of chemotherapy
• CNS disease is any malignant cell present in the CSF regardless of cell count.

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 PEDIATRIC HODGKIN LYMPHOMA
Treatment algorithm: Pediatric Hodgkin Lymphoma

Hodgkin Lymphoma

Low risk Intermediate risk High risk

2# OEPA/ABVD 2#OEPA/ABVD/ABVE-PC 2#OEPA/ABVD/ABVE-PC/BEACOPP

CECT or
FDG-PET CT scan (a) (response assessment table below)

 RT ( for OEPA patients) 2# COPDac/COPP  RT* or 4# COPDac RT* or

or 2# ABVD  RT* 4# ABVD + RT* 4# ABVD + RT*
1-3# ABVE-PC  RT* 1-3# ABVE-PC  RT*
2-4#BEACOPP  RT*

Chemotherapy regimens

BEACOPP: Bleomycin, Etoposide, Doxorubicin, Cyclophosphamide, Vincristine, Procarbazine, and

Prednisone

ABVD: Doxorubicin, Bleomycin, Vinblastine, and Dacarbazine

ABVE-PC: Doxorubicin, Bleomycin, Vincristine, Etoposide, Prednisone, Cyclophosphamide

OEPA: Vincristine, Etoposide, Prednisone, Doxorubicin

COPDac: Cyclophosphamide, Vincristine, Prednisone, Dacrbazine

*RT indicated only for inadequate response (PET)/ bulky disease denoted as (X) in the staging at presentation

RT doses ranging from 19.8 cGy to 25 cGy

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Diagnostic workup

1 History and B symptoms (any one is sufficient)

physical Fever (oral temp >38’C)
examination Night sweats
Weight loss > 10% in last 6 months
2 Laboratory Baseline labs CBC, Renal function test, Liver function test, serum
electrolytes LDH Coagulation profile, Viral Markers (b)
Bone marrow aspirate and biopsy for stage IV only (b)
CSF cytospin and morphology only if indicated (b)
3 Imaging CXR
CT scan chest abdomen and pelvis (if PET not available)
OR
PET scan whole body (a)
2D ECHO (a)
4 Histology Excision biopsy of a peripheral lymph node or
Core biopsy of mediastinal or abdominal lymph node if no
accessible enlarged peripheral node
Immunohistochemistry as in appendix (a)

Staging information (Ann-Arbor staging system)

Stage I Involvement of a single lymphatic site (ie. nodal region, Waldeyer’s ring, thymus,
spleen) (Stage I); or involvement of a single extralymphatic organ or site in the
absence of any lymph node involvement (Stage IE)
Stage II Involvement of two or more lymph node regions on the same side of the diaphragm
(Stage II) or localized involvement of a single extra lymphatic organ or site in
association with regional lymph node involvement with out without involvement of
other lymph node regions on the same side of the diaphragm (Stage IIE)
Stage III Involvement of lymph node regions on both sides of the diaphragm (Stage III) which
may also be accompanied by extra lymphatic extension in association with adjacent
lymph node involvement (Stage IIIE) or by involvement of the spleen or both (Stage III
ES)
Stage IV Diffuse or disseminated involvement of one or more extra lymphatic organs, with or
without associated lymph node involvement; or isolated extra lymphatic organ
involvement in the absence of adjacent regional lymph node involvement, but in
conjunction with disease in distant site(s). Stage IV includes any involvement of the
liver or bone marrow, lungs (note) or CSF.
The substage classification A,B,E,S,X amend each stage based on defined features
B - B symptoms, A - absence of B symptoms. S - Spleen Involvement E - extra-nodal extension which most
commonly involves lung, pleura, pericardium or bone when there is contiguous extension of lymph node
disease or the site is proximal to an involved draining lymph node. X - Bulky disease defined differently by
various study groups. Bulky peripheral lymphadenopathy is defined as single or conglomerated lymph
nodal mass >6cm in longest diameter. Bulky mediastinal disease is defined as a mediastinal mass with a
horizontal tumor diameter ≥1/3rd the thoracic diameter.

NCG PHL AND PST 2020 18

 APPENDIX A (FLOWCYTOMETRY)
A. Acute Leukemia- Essential panel (a)

1. Smears stained with a Romanowsky stain and Myeloperoxidase or Sudan Black B

2. NSE, toluidine blue and Iron stain as required.

Note: Morphology is followed by flow cytometricimmunophenotyping and other ancillary techniques

including cytogenetics and molecular diagnostics. The final diagnosis is based on a combination of all these
modalities.

Essential
Common markers CD45, CD38, HLADR
Markers of immaturity CD34
Lineage associated Lineage Specific
B-cell CD10, CD19, CD20, surface or
cytoplasmic CD22, CyCD79a
T-cell CD1a, CD4, CD5, CD7, CD8, Surface and Cytoplasmic CD3
TCRγδ
Myeloid CD13, CD33, CD117 cyMPO or Cytochemical
Myeloperoxidase or Sudan Black B
Monocytic CD36, CD64 Non Specific Esterase
Megakaryoblastic X
NK-cell CD56
Plasmacytoid dendritic CD123
cells

B. Acute leukemia – Optimal panel (b)

Essential + additional markers as below

Optimal Lineage associated Lineage Specific

B - cell CD73, CD86, CD25, CD304
T - cell
Myeloid CD15
Monocytic CD11c, CD14
Megakaryoblastic CD41, CD61
NK – cell
Plasmacytoid dendritic
cells

NCG PHL AND PST 2020 19

C. Acute leukemia – Optional panel (c)

Optional
Common markers CD25, CD45Ra
Markers of immaturity CD133, TdT
Lineage associated Lineage Specific
B - cell CD58, CD81, NG2, CRLF2 IgM, Kappa & Lambda chains
T - cell CD2, CD99, TCRαβ
Myeloid CD15, CD11b, CD16, CD65,
CD66c
Monocytic CD86, CD300e
Megakaryoblastic CD42b
NK-cell CD94, CD161
Plasmacytoid dendritic cells CD303, CD304
Mast cells CD203c
Erythroid lineage CD49d, CD71, CD105 CD235a

D. DNA ploidy by flow cytometry for B-ALL – Optimal (b)

Propidium Iodide
FxCycle Violet
DRAQ5
DAPI (4’,6-Diamidino-2-phenyl Indole)

E. B-ALL Minimal Residual Disease Panel Essential (a) + Optional (c)

Essential Optimal Optional

CD10, CD19, CD20, CD34, CD38, CD45, CD25, CD44, CD66c, CD81, CD200, CD58
CD73, CD123, CD86, CD304
Nuclear dye such as Syto13, Syto16,
Syto44

Recommendations for processing

- Use Euroflow recommended Bulk-lysis method
- Acquire minimum 10,00,000 CD45-positive events
- Minimum 8-color antibody panel
- Use the template-based analysis
- Should be done in a laboratory with workload of minimum 30 acute leukemia samples per month
- Mention the limit of detection and limit of quantitation of MRD assay
- Mentioned the number of events studied
- Control sample should be evaluated atleast once in month

NCG PHL AND PST 2020 20

F. T-ALL MRD Optimal (b) + Optional (c)

Optimal Optional

CD4, CD5, CD7, CD8, CD16, CD34, CD38, CD45, CD56, CD1a, CD2, CD48, CD99, TdT
Surface and cytoplasmic CD3
Nuclear dye such as Syto13, Syto16, Syto44 -

G. AML MRD Optimal (b) + Optional (c)

Optimal Optional

Deviation from normal CD13, CD14, CD15, CD33, CD34, CD36, CD11b, CD65, CD66c,
CD38, CD45, CD64, CD117, CD123, HLADR CD71,
Leukemia associated CD7, CD19, CD56 CD2, CD4, CD5,
Immunophenotypic
markers

H. Lymphoproliferative disorders/Lymphoma Essential (a) + Optimal (b) + Optional (c)

B-cell NHL

Essential Optimal Optional

CD5, CD10, CD19, CD20, CD23, CD22, CD38, CD27, CD43, CD44, CD49d, CD72, CD79b,
CD45, CD200, Kappa & Lambda IgM, CD81, CD123, CD148, CD180, CD305, IgD,
light chains IgG, FMC7, ROR1, Ki67, BCL2, BCL6, Mum-1

T- NHL

Essential Optimal Optional

CD3, CD4, CD5, CD7, CD8, CD10, CD2, CD30, CD94, CD38, CD45RA, CD45RO, TCL1,
CD16, CD25, CD26, CD45, CD56 CD161, CD185, CD279, TCRVβ-repertoire, KIR, Ki67, TIA-1
ALK-1, Perforin,
Granzyme

Important: The laboratory without expertise in diagnosing hematolymphoid neoplasms and with
inadequate IHC/Flow cytometricimmunophenotyping panels should refer the sample to any specialized lab
dealing with such neoplasms. There cannot be any definite algorithms for diagnosing hematolymphoid
neoplasms as each lesion is different and number of reagents used may vary case to case basis.

NCG PHL AND PST 2020 21

APPENDIX B

Histopathology for lymphomas

Tissue /lymph node processing guidelines

Essential
• Tissue preservation (avoid frozen processing)
• Fixative: 10% neutral buffered formalin
• Fixation:
• Lymph nodes/tissue thicker than 0.8 -1.0cms; should be bisected and large tissue should be
serially sliced, perpendicular to the long axis.
• Tissue ≤4 cm in greatest dimension should be processed in entirety
• Should be put for fixation within 30 – 60 minutes of biopsy
• Fixation volume should be at 3-4 times the volume of the tissue
• Should not be left in the fixative for more than 48 hrs; and should be processed in 12-24 hrs time
(in cases of inevitable delay; should be kept in cold temperature [refrigerator], preferably at 4
degrees centigrade)
• Routine processing and embedding
• 2-3 micron thick sections with Hematoxylin and eosin stained slides of each paraffin block
• Immunohistochemistry set up
• Microscopic evaluation
Optional (Immunohistochemistry and Molecular diagnostic laboratories)
*For transportation – Either by immersing tissue in the adequate formalin in a sealed container or by
paraffin blocks

Lymphoma Tissue Diagnosis

Essential: (a)
• Diagnosis:
• Histological evaluation, i.e. biopsy as a method of investigation with comprehensive IHC panels.
• Only in instances of inability of get adequate, a fine needle aspiration (FNA) based flow
cytometric evaluation should be considered for diagnosis
• Staging
• Bone marrow biopsy, aspirate and imprint smear

Optional/extended work-up: (b)

• Diagnosis:
• Fine needle aspiration (FNA) based flow cytometricimmunophenotyping along with the biopsy
• Molecular work-up (c)
• Staging:
• Flow cytometricimmunophenotypic evaluation (for Non-Hodgkin Lymphoma) (c)

A. Hodgkin lymphoma
(cHL) classical Hodgkin Lymphoma and (NLPHL) Nodular Lymphocyte Predominant Hodgkin Lymphoma-
requisites for diagnosis

NCG PHL AND PST 2020 22

Classic Hodgkin lymphoma (cHL)
• Essential: (a)
• CD3, CD20, CD30, CD15, Pax5, ALK-1**
• Optimal/extended work-up: (b)
• LCA, CD3, CD20, CD30, CD15, Pax-5, Oct2, Bob1, EBV-LMP1/EBER, Gata 3

Nodular lymphocyte predominant Hodgkin lymphoma (NLPHL)

• Essential: (a)
• CD20, CD3, CD30, CD15, Pax5
• Optimal/extended work-up: (b)
• CD3, CD20, CD30, CD15, Pax-5, EBVLMP1/EBER, PD1, Oct2, Bob1, Gata3, CD4, CD8
** Rule out a possibility of ALK+ve ALCL

B. Non-Hodgkin Lymphoma
1. CD20 positive BNHL: large cell morphology
• Essential: (a)
• IHC: LCA, CD20, CD3, MIB-1
• Optimal/extended work-up:
• IHC: CD3, CD20, MIB-1, cyclin D1, CD5, CD10, Bcl6, Mum1, cmyc, Bcl-2, CD30, EBV-LMP1/EBER
• FISH: CMYC/BCL2/BCL6 gene rearrangement
• Gene expression/methylation studies – COO subtyping

2. CD20 positive BNHL: non-large cell morphology

• Essential: (a)
• IHC: LCA, CD20, CD3, MIB-1, CD5, CD23, CD10, bcl6, cyclin D1 (if blastic morphology, please add
AMPO, ckit, CD10, CD19/Pax5, Tdt, CD34)
• Optimal/extended work-up: (b)
• IHC: Mum1, cmyc, Bcl-2, EBV-LMP1/EBER, CD43, CD138, Sox11
• FISH: CMYC/BCL2/BCL6; IFR4 gene rearrangement
• Sequencing: MYD88 mutation

3. CD3 positive NHL: large cell morphology

• Essential: (a)
• IHC: CD20, CD3, CD30, MIB-1, ALK-1, CD4
• Optimal/extended work-up :
• IHC: CD3, CD20, CD4, CD8, CD2, CD5, CD7, MIB-1, CD56, CD30, ALK-1, CD10, Bcl6, PD1, Mum1,
EBV-LMP1/EBER, CD123, Gata3
• FISH: DUSP22 gene rearrangement

4. CD3 positive NHL: non-large cell morphology

• Essential: (b)
• IHC: CD20, CD3, CD2, CD5, CD7, CD4, CD8, MIB-1, cyclin D1, Tdt, CD34, CD30, ALK-1
• Optimal/extended work-up :
• IHC: CD56, CD10, Bcl6, PD1, Mum1, EBER-ISH, CD123, Gata3, CXCLl13, CXCR5, ICOS
• FISH: DUSP22 gene rearrangement

NCG PHL AND PST 2020 23

5. CD3 and CD20 negative NHL- requisites for diagnosis
• IHC: LCA, CD3, CD20, CD30, CD19, Pax-5, CD138, ALK-1, CD5, CD10, Bcl6, Mum1, EBV-LMP1/EBER,
CD56, CD7, CD4, CD8, CD123, MIB-1, c-kit, MPO, CD41, CD61, CD33, CD34, Tdt, CD1a, CD163, S-100
protein, EMA, CD23, CD21, kappa, lambda, MIB-1

Important: The laboratory without expertise in diagnosing hematolymphoid neoplasms and with
inadequate IHC/Flow cytometricimmunophenotyping panels should refer the sample to any specialized lab
dealing with such neoplasms. There cannot be any definite algorithms for diagnosing hematolymphoid
neoplasms as each lesion is different and number of reagents used may vary case to case basis.

NCG PHL AND PST 2020 24

APPENDIX C

Response assessment for Lymphomas

Deauville score

1 No FDG uptake
2 FDG uptake < mediastinum
3 FDG uptake > mediastinum but < liver
4 FDG uptake > liver at any site
5 FDG uptake > liver and new sites of disease
x New areas of FDG uptake unlikely to be related to lymphoma

NCG PHL AND PST 2020 25

 PEDIATRIC SOLID TUMORS

NCG PHL AND PST 2020 26

 WILMS TUMOUR
Treatment Algorithm: Wilms Tumor

Suspected Wilms Tumour

Essential: US abdomen, CT scan thorax, abdomen and pelvis (a),

Optimal: USG doppler, MRI for Bilateral WT and nephroblastomatosis (b)

Unilateral Renal Mass Bilateral Renal Mass

Borderline/unresectable on imaging
Resectable on imaging Upfront chemotherapy: 6-12
Or stage 4
weeks VAD

Upfront surgical resection Optional: Image guided core

biopsy/ FNAC (b)
CT Scan for reassessment

Nephrectomy with lymphnode

sampling Wilms tumour
Bilateral partial nephrectomy/ unilateral
partial nephrectomy and nephrectomy
Wilms tumour for worse side withlymphnode sampling
Upfront chemotherapy 4-6 weeks
VA (VAD for stage 4)
Non-Wilms CT Scan for reassessment
tumor
Nephrectomy with lymphnode sampling

Treatment as per
histology
Surgico-pathologic stage assessment*
Optional: LOH1p/16q and 1p gain (c)

Stage 1 & 2 FH Stage 3 FH, Stage 1-3 Stage 4 FH, FA Stage 2 -4 DA

FA, Stage 1 DA

Total 18 weeks VA
Total 24 weeks VAD + Total 24 weeks VDCE or
local RT Total 24 weeks VAD + Local RT (as per 30 weeks of VDCEJ + RT
local stage) + RT/Surgery for metastases
• FH=Favourable Histology
• V= Vincristine, A= Actinomycin D, D= Doxorubicin, C= Cyclophosphamide, E= Etoposide, J= Carboplatin
• RT= Radiotherapy
• DA- diffuse anaplasia, FA-focal anaplasia

NCG PHL AND PST 2020 27

 • Tumours weighing <550g in children aged <24 months and with favorable histology may be observed
after surgery
• In centres adopting the SIOP approach to management of Wilms tumor, post-operative chemotherapy is
given as per operative staging and post-operative histology as per table below:

Risk Stratification
Disease Treatment
Stage I Stage II Stage III
Low-risk None AV (27 weeks) AV (27 weeks)
Intermediate-risk, all subtypes <500ml AV (4 weeks) AV (27 weeks) AV (27 weeks) + flank RT
Intermediate-risk, stromal or AV (4 weeks) AV (27 weeks) AV (27 weeks) + flank RT
epithelial-type >500 ml
Intermediate-risk, nonstromal, AV (4 weeks) AVD (27 weeks) AVD (27 weeks) + flank RT
nonepithelial
High-risk blastemal type and diffuse AVD (27 weeks) DCEJ (34 weeks) DCEJ (34 weeks)
anaplasia Wilms tumour flank RT in DA + flank RT

Staging of Wilms Tumour

Stage 1 Tumour limited to the kidney and completely excised.
Stage 2 Tumour extends beyond the kidney but is completely excised
The tumour infiltrates the renal sinus and/or adjacent organs or vena cava but is completely
resected
Stage 3 Residual nonhematogenoustumor confined to the abdomen; lymph-node involvement,
peritoneal spillage, peritoneal implants, either gross or microscopic tumor beyond the
surgical margin, or tumor not completely removed.
Stage 4 Hematogenous metastases to lung, liver, bone, brain or other organ.
Stage 5 Bilateral renal involvement at diagnosis.

NCG PHL AND PST 2020 28

 RT guidelines in Wilms Tumour
Abdominal Tumour Stage/ Histology RT Dose (RT Field)
1. Stage I & II/ Favorable No RT
2. Stage III/ Favorable and Focal Anaplasia 10.8Gy/ 6# @ 1.8Gy/ Fraction (level Ib)
3. Stage I – II/ Diffuse Anaplasia 10.8Gy/ 6# @ 1.8Gy/ Fraction
4. Stage III/ Diffuse Anaplasia 19.8Gy/ 11# @ 1.8Gy/ Fraction
5. Recurrent Abdominal Disease 10.8Gy/ 6# @ 1.8Gy/ Fraction
6. Lung Mets (Favorable & Unfavorable)
Microscopic Disease 12.6Gy/ 7# @ 1.8Gy/ Fraction
Gross Disease/ Nodules + 9.0Gy/ 5# @ 1.8Gy/ Fraction (Boost)
7. Liver Mets (Favorable & Unfavorable 10.8Gy/ 6# @ 1.8Gy/ Fraction (Whole Liver)
Histology) + 9.0Gy/ 5# @ 1.8Gy/ Fraction (Boost to Gross
residual disease)
8. Skeletal Mets (Favorable& Unfavorable Histology) 25.2Gy/ 14# @ 1.8Gy/ Fraction (Lesion + 3cm)
9. Unresected Lymph Nodal Mets (Favorable& 19.8Gy/ 11# @ 1.8Gy/ Fraction (Nodal Region)
Unfavorable Histology)

• Whole-lung irradiation may be omitted in cases of FH with complete response (pulmonary) after 6
weeks of VAD (provided there is no extrapulmonary metastases or LOH 1p/16q)
• 3D Conformal RT and Intensity Modulated RT are standard forms of delivery of RT in children with
WT

NCG PHL AND PST 2020 29

NEUROBLASTOMA
Treatment Algorithm: Neuroblastoma

Suspected Neuroblastoma

Essential: US and CT scan of primary tumor site, MIBG scan /Whole body FDG-PET scan ,Biopsy of primary
, n-Myc status by FISH, B/L Bone marrow biopsy (a)
Optimal: Urinary VMA, Segmental chromosomal anomalies, MRI ( paraspinaltumours) (b)
Optional: Bone Scan (c)

Very low risk Low risk Intermediate risk High risk

Surgery followed
by Observation
LTS LTS Unresectable Resectable
absent present

Induction/Neoadjuvant Upfront surgery

Active 1-2 cycles of
chemotherapy *
surveillance chemotherapy*
+/- surgery.
CT reassessment

Surgery ***
Induction/Neoadjuvant
chemotherapy**

Adjuvant Reassessment withPET/

Chemotherapy(Total 4-8 MIBG. CECT/MRI of local part
cycles)* and Bone marrow biopsy

Surgery
LTS: Life threatening symptoms
*Chemotherapy regimens for low/Intermediate Risk Neuroblastoma
-Carboplatin and Etoposide,
-Cyclophosphamide and doxorubicin High dose chemotherapy and
**Chemotherapy regimens (NACT) for High risk Neuroblastoma Autologous stem cell transplant
-OPEC/OJEC:vincristine, cisplatin, etoposide, cyclophosphamide, and (ASCT)
carboplatin
-Rapid COJEC: carboplatin, etoposide, vincristine, cisplatin and Radiotherapy to primary19.8Gy and
cyclophosphamide bony metastatic sites
-ICE: Ifosfamide, Cisplatin, Etoposide
-N7 protocol: cyclophosphamide, doxorubicin, vincristine, cisplatin and
etoposide
*** May consider local radiation therapy or MIBG therapy in inoperable Maintenance therapy with 13-cis
tumours
retinoic acid

NCG PHL AND PST 2020 30

 Risk Stratification

International Neuroblastoma Risk Grouping Staging System (INRGSS)

Stage Description
L1 Localized tumor not involving vital structures as defined by the list of Image defined Risk
Factors (IDRFs) and confined to one body compartment.
L2 Loco regional tumor with presence of one or more image defined risk factors
M Distant metastatic disease (except stage MS)
MS Metastatic disease in children younger than 547 days and metastases confined to skin, liver
and/or bone marrow (< 10% of total nucleated cells on smears or biopsy)

International Neuroblastoma Risk Grouping

Very low Risk Infant (<18 months) asymptomatic, no high-risk molecular features, Ganglioneuroma any age

Low Risk Infant (<18 months) NB L2 or stage II/III (non-metastatic)

Intermediate Stage M infant (<18 months) NB, Stage II/III, L2 non-infantile NB, infant (<18 months) NB L2 or
Risk stage II/III with 11q aberration

High Risk Any NMYC amplified tumour, Metastatic Stage M(non-infant), infant NB MS with 11q
aberration

NCG PHL AND PST 2020 31

 HEPATOBLASTOMA
Treatment Algorithm: Hepatoblastoma

Suspected Hepatoblastoma

Essential: US abdomen, CT thorax and abdomen (Triphasic) Serum Alfa Fetoprotein (AFP)(a)
Optimal: MRI Liver (b)

No Radiology consistent with hepatoblastoma

Biopsy Age 6months-3 years, High S.AFP

Yes. (Biopsy not mandatory)

Hepatoblastoma
Non-hepatoblastoma

Treat as per histology Standard risk High risk

Chemotherapy with
Neo-adjuvant Chemotherapy
Cisplatin 2-4 cycles
PLADO/ C5V/SUPER PLADO
4-7 cycles

CT scan for Reassessment CT scan for Reassessment

Surgery* Surgery: liver resection**

Adjuvant chemo (Cisplatin Adjuvant Chemotherapy

total 6 cycles)

*Upfront surgical resection may be feasible in selected cases of Standard Risk hepatoblastoma
**Orthotopic liver transplant indicated in selected cases of high risk hepatoblastoma requiring extensive
resection( multifocal/ pretext IV)
• PLADO: Cisplatin + Doxorubicin, (Total 6 cycles)
• C5V – Cisplatin + 5-fluorouracil+ Vincristine ( Total 6 cycles)
• SUPERPLADO : Alternating cycles of Carboplatin/Doxorubicin and Cisplatin ( total 10 cycles)

NCG PHL AND PST 2020 32

Risk Stratification

High risk: Patients with any of the following Standard risk

Serum alpha-fetoprotein <100 μg/l All other patients
PRETEXT IV
Small cell undifferentiated subtype
Additional PRETEXT criteria:
Extrahepatic intra-abdominal disease (E).
Distant metastases (M ),
Nodal metastases (N1, N2)
Tumor extension into the main and/or both branches of the portal vein (P2, P2a)
Tumor extension into the vena cava or all three hepatic veins (V3, V3a )
Intraperitoneal Haemorrhage (H1)

NCG PHL AND PST 2020 33

RETINOBLASTOMA
Treatment Algorithm: Retinoblastoma

Intraocular Mass (Suspected Retinoblastoma)

Essential: B scan Ultrasound, MR Orbit + Screening Brain, Examination under Anaesthesia (a)

In extra-ocular disease or optic nerve involvement: B/L Bone Marrow aspirate/biopsy, CSF cytology (a)

Optimal: NGS for Germ Line Mutation (b) Optional: CT Orbit + Screening Brain (c)

Unilateral RB Bilateral RB

Grouping for Intraocular Retinoblastoma

Group A Small tumors away from foveola and disc

• Tumors < 3 mm, confined to the retina, and
• Located at least 3 mm from the foveola and 1.5 mm from the optic nerve.
Group B All remaining tumors confined to the retina
• all other tumors confined to retina and not in Group A
• Subretinal fluid (without subretinal seeding) <3 mm from the base of the tumor.
Group C Local vitreous or subretinal seeding
• Subretinal fluid alone > 3mm and < 6 mm from the tumor
• Vitreous or subretinal seeding < 3mm from the tumor
Group D Diffuse vitreous or subretinal seeding
• Subretinal fluid alone > 6 mm from the tumor
• Vitreous or subretinal seeding > 3mm from the tumor

Group E Presence of any one or more of these poor prognosis features

• More than 2/3 of the globe filled with tumor
• Tumor in anterior segment or anterior to vitreous
• Tumor in ciliary body
• Iris neovascularisation
• Neovascular glaucoma
• Opaque media from hemorrhage
• Tumor necrosis with aseptic orbital cellulitis
• Phthisis bulbi

Genetic counseling needs to be done in all families, with genetic testing indicated in cases of suspected
heritable disease
Screening of all siblings less than 7 years of age should be done

NCG PHL AND PST 2020 34

 Treatment Algorithm: Retinoblastoma- Unilateral

Unilateral RB

Intraocular A-C Advanced E with

Intraocular D unfavourable features
+ very selective E

Group A Group B, C**

$ Primary Enucleation
2-3 #VEC f/b re-evaluation **

Good Response Poor /Suboptimal

Focal therapy 2-3 # VEC f/b response
reevaluation
Consolidate with focal
therapy+ Total 6# VEC Adjuvant Chemotherapy
Good Response as per Pathology
chemotherapy
+total 6#VEC
Poor Response
Consolidation with focal therapy
+ Total 6# VEC chemotherapy
Ophthalmic Artery
Chemoinfusion(3 sessions) Secondary Enucleation

Good Response Poor Response

Consolidation with Focal Secondary enucleation Adjuvant Chemotherapy as

Therapy per Pathology (total 6
cycles VEC)

Adjuvant Chemotherapy as
per Pathology

• Extraocular disease: 12 cycles of chemotherapy(VEC), Secondary Enucleation ( after 2-4 cycles) and EBRT
• Response assessment
-Intraocular disease : by Examination Under Anaesthesia (EUA) and periodic B-ultrasound (a)
-Extraocular disease : Additionally, requires MRI (a)

NCG PHL AND PST 2020 35

 Treatment Algorithm: Retinoblastoma- Bilateral

Bilateral RB

Symmetric disease Asymmetric disease

To plan treatment
Group A Group B, C** Group D,E according to the
advanced eye

Focal therapy 2-3 # VEC f/b reevaluation 6 # VEC + focal

consolidation after 2-3 # $

Good response Progression Good response Progression

Consolidation with focal Ophthalmic artery Follow-up Secondary Enucleation

therapy for both eyes, (Total 6 chemoinfusion
cycles VEC

Adjuvant treatment
depending on pathology*

• Extraocular disease: 12 cycles of chemotherapy(VEC), Secondary Enucleation ( after 2-4 cycles) and EBRT
• Response assessment
-Intraocular disease : by Examination Under Anaesthesia (EUA) and periodic B-ultrasound (a)
-Extraocular disease : Additionally, requires MRI (a)

NCG PHL AND PST 2020 36

Unfavorable features in group E disease: Phthisis bulbi, Intraocular haemorrhage, neovascular glaucoma, anterior
chamber involvement

Focal therapies
-Laser photocoagulation
-TranspupillaryThermo Therapy
-Cryotherapy
-Plaque RT
** To consider ophthalmic artery chemoinfusion/ intra-arterial chemotherapy case to case basis and
where expertise available
$
To consider intravitreal chemotherapy in group D/E

Chemotherapy details

Chemotherapy :VEC (Vincristine, etoposide, Carboplatin)

-6 cycles for Intraocular disease
-12 cycles for extraocular/stage 3 disease (plus EBRT)
Other chemotherapy Options:
-High dose carboplatin
-Vincristine/doxorubicin/cyclophosphamide (refractory group E tumours/ stage 3 disease)
Stage 4 Bone Marrow disease:
-Chemotherapy including high dose chemotherapy with Autologous BMT /Stem Cell Transplant
Stage 4 Central nervous system disease.
-Treatment intent to be decided on a case-to case basis by MDT. To consider palliation
*Indications for Adjuvant Chemotherapy:
-Massive choroidal infiltration
-Post-laminar optic nerve involvement (PLONI)
-Scleral or Extra-scleral spread (on radiology or HPR)
-Cut-margin of Optic Nerve positive for tumor,
-Optic Nerve involvement upto the apex at presentation on MRI
*Indications for Adjuvant Radiotherapy:
-Extra-scleral spread
-Cut-margin of Optic Nerve positive for tumor on histology
-Extra-ocular mass at presentation
-Optic Nerve involvement upto the apex at presentation on MRI

NCG PHL AND PST 2020 37

Radiotherapy doses:
-Definitive RT 45Gy/25#s over 5 weeks with conformal portals
-Adjuvant RT 39.6Gy/22#s over 5 weeks with conformal portals

EXTRACRANIAL GERM CELL TUMOUR

Treatment Algorithm: Extra Renal Germ Cell Tumor

Suspected Germ Cell Tumor

Essential: S. AFP, B HCG, CT scan of thorax, abdomen and pelvis, Biopsy of mass ( if tumor markers normal) (a)

Optimal: MRI for paraspinal/pelvic or intraspinal disease (b)

Intermediate risk High risk

Low risk

3 # PEb/JEb
Surgery feasible Inoperable
Surgery f/b CT scan reassessment
Observe & monitor Tumor markers
Tumor markers
Surgery 3-4 # PEb/4#JEb Surgery of primary+/-
metastatectomy
CT scan reassessment Tumor markers
\

3-4 # PEb/4#JEb Surgery

Failure of Adjuvant chemotherapy Total
tumour markers
\ 4-6 # PEb/6 #JEb
to normalize /
recurrence
NCG PHL AND PST 2020 38
 Markers normalize Residual disease (If Progressive disease
operated upfront)
Markers normalize -
continue observation 2nd Line CT- VeIP/TIP/TIC
Second look Surgery

No viable tumor Tumor Marker

Tumor Markers Normal Raised and/or tumor
Mature Teratoma Viability

Observe 2 # PEb/JEb

Chemotherapy:
PEb: Cisplatin d1-d5, Etoposide d1-d5, Bleomycin d1 (3-4 cycles in Intermediate Risk and 4-6 cycles in High
Risk)

JEb: Carboplatin d1, Etoposide d1-d3, Bleomycin d1 (4 cycles in Intermediate Risk and 6 cycles in High Risk)

VeIP: Vinblastine d1, Ifosfamide d1-d5, Cisplatin d1-d5 (6 cycles)

TIP: Paclitaxel d1,Ifosfamide d2-d5, Cisplatin d2-d5 (4-6 cycles)

TIC: Paclitaxel d1, Ifosfamide d2-d5, Carboplatin d1 (4-6 cycles)

Risk stratification
Low risk: Stage I testes
Stage I ovary
All immature teratoma (completely excised)
Intermediate risk: Stage II- IV testes
Stage II-III ovary
Stage I-II Extragonadal
Immature teratoma (incompletely excised)

High risk: Stage IV ovary

Stage III-IV Extragonadal

Tumour markers (Serum Alfa-fetoprotein, AFP and Serum Beta HCG) to be done at diagnosis. If raised,
monitoring of disease status may be done by measurement of tumor markers after each cycle of
chemotherapy, surgery and at end of treatment. Post treatment surveillance to be done using tumor
markers.

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NCG PHL AND PST 2020 40
 RHABDOMYOSARCOMA
Treatment Algorithm: Neuroblastoma

Suspected Rhabdomyosarcoma

Essential: CT scan of chest/ abdomen/pelvis, MRI scan for extremity and head/neck primary/genitourinary RMS (must
evaluate draining lymph nodes with MRI/USG), Bone scan,Biopsy of mass, B/L bone marrow biopsy (a)

Optimal: Molecular studies on tissue specimen (PAX-3 FKHR, PAX-7 FKHR fusion status) Whole body PET CT scan (b)

Low risk Intermediate risk High risk

High risk due to “only”

Pulmonary metastases

Chemotherapy All other than “only”

(VA/VAC/VIE) lung metastases
Neoadjuvant chemotherapy-9-12 weeks
VAC/ VIE/ IVA/IVADo/ VDC-IE/VIrn
CT/MRI reassessment

CT/MRI reassessment
Surgery to primary
(or definitive RT to primary in
*Local treatment: To be discussed in joint clinic
orbit )
Surgery and/or Radiotherapy and individualization of care
including palliation

Adjuvant chemotherapy
(VA/VAC/VIE) Adjuvant chemotherapy
VAC/ VIE/ IVA/IVADo/ VDC-IE/VIrn

Chemotherapy Options:

• VA: Vincristine, Dactinomycin (for low risk only)

• VAC: Vincristine, Dactinomycin, Cyclophosphamide
• VIE: Vincristine, Ifosfamide, Etoposide
• IVA: Ifosfamide, Vincristine, Dactinomycin
• IVADo: Ifosfamide, Vincristine, Dactinomycin, Doxorubicin
• VDC-IE :Vincristine, Doxorubicin, Cyclophosphamide/Ifosfamide, Etoposide
• VIrn :Vincristine/Irinotecan

NCG PHL AND PST 2020 41

 *Local Therapy options:Complete surgical excision only (upfront surgery)

Complete Surgical excision followed by Radiotherapy(or brachytherapy)

Definitive Radiotherapy (inoperable)

(Indications and doses for adjuvant radiation are given below)

Radiotherapy Guidelines for Rhabdomyosarcoma

S.No. Site / Stage / Histology RT Field RT Dose

1. Group I
Embryonal No RT
Alveolar Pre - Chemotherapy primary site 36Gy
2. Group II
N0 (microscopic residual disease after Pre - Chemotherapy primary site 36Gy
surgery)
N1 (resected regional lymph node Pre - Chemotherapy primary site + 41.4Gy
involvement) Nodes
3. Group III
All Pre - Chemotherapy primary site 50.4Gy (45 Gy for orbital
tumors in complete
remission)
Patients undergoing delayed surgical Pre-chemotherapy primary site 36Gy
resection with negative margins
4. Group IV Treat primary site as for other
groups + all metastatic sites if
technically feasible & safe

Staging based on the TNM and site of disease:

Stage Sites of Primary Tumor T Stage Tumor Size Regional Lymph Nodes Distant
Metastasis

I Favorable sites T1 or T2 Any size N0 or N1 or NX M0

II Unfavorable sites T1 or T2 a- 5 cm N0 or NX M0

III Unfavorable sites T1 or T2 a- 5 cm N1 M0

b- > 5 cm N0 or N1 or NX

IV Any site T1 or T2 Any size N0 or N1 or NX M1

M0 = absence of metastatic spread; M1 = presence of metastatic spread beyond the primary site; N0 =

NCG PHL AND PST 2020 42

absence of nodal spread; N1 = presence of nodal spread beyond the primary site; X = unknown N status.

Grouping based on the surgico-pathological resection

Group Definition
I A localized tumor that is completely removed with pathologically clear margins and no regional
lymph node involvement.
II A localized tumor that is grossly removed with (a) microscopic disease at the margin, (b)
involved, grossly removed regional lymph nodes, or (c) both (a) and (b).
III A localized tumor with gross residual disease after incomplete removal or biopsy only.
IV Distant metastases are present at diagnosis.

Risk stratification of RMS

Risk Group Histology Stage Group

Low risk Embryonal / (Fusion negative) 1 I, II, III
Embryonal / (Fusion negative) 2, 3 I, II
Intermediate risk Embryonal / (Fusion negative) 2, 3 III
Alveolar / (Fusion positive) 1, 2, 3 I, II, III
High risk Embryonal or Alveolar (Fusion negative/positive) 4 IV

NCG PHL AND PST 2020 43

NASOPHARYNGEAL CARCINOMA
Treatment Algorithm: Nasopharyngeal Carcinoma

Suspected nasopharyngeal carcinoma

Essential: CT scan of head and neck and chest, Bone scan for staging, Biopsy of
mass or cervical lymph node(a)
Optimal: MRI head and neck, FDG PET, Pure tone Audiometry (b)

Options:

• 2# BMP> Radiotherapy > 2 # of BMP

• 3# 5FU+leucovorin+Cisplatin > CTRT (cisplatin + radiotherapy)

Reassessment prior to RT with CT scan

Chemotherapy:

BMP: Bleomycin, Methotrexate, Cisplatin

5FU+CDDP: 5 Fluorouracil+/- Leucovorin, cisplatin

Radiotherapy :

Dose: 55-70 Gy given in fractions of 1.6-2.1 Gy in 33 fractions over 7 weeks

Intensity modulated radiotherapy with/without image guidance

NCG PHL AND PST 2020 44

 ANNEXURE -1
DIAGNOSTIC INVESTIGATIONS FOR COMMON PAEDIATRIC SOLID TUMOURS

Tumor Local/staging Essential (a) Local Staging Optimal

(b)/Optional (c)
All Paediatric Solid tumours USG abdomen to be part of basic diagnostic workup
Neuroblastoma CT scan of primary tumor site Urinary VMA
MIBG scan/Whole body FDG-PET scan
Biopsy of mass Segmental chromosomal
n-Myc status by FISH anomalies
B/L Bone marrow biopsy MRI ( paraspinaltumours) (b)
Bone Scan (c)
Wilms Tumor CT scan thorax, abdomen and pelvis USG doppler
MRI for Bilateral WT and
nephroblastomatosis (b)
Hepatoblastoma CT thorax and abdomen (Triphasic) MRI Liver (b)
Serum Alfa Fetoprotein (AFP)
Rhabdomyosarcoma CT scan of chest/ abdomen/pelvis Molecular studies on tissue
specimen (PAX-3 FKHR, PAX-7
MRI scan for extremity and head/neck FKHR fusion status) Whole body
primary/genitourinary RMS PET CT scan (b)
Bone scan
Biopsy of mass
B/L Bone marrow biopsy
Germ Cell Tumor S. AFP, B HCG MRI for paraspinal/pelvic or
intraspinal disease (b)
CT scan of thorax, abdomen and pelvis
Whole body PET CT scan (c)
Biopsy of mass (if tumor markers normal)
Retinoblastoma B scan Ultrasound NGS for Germ Line Mutation (b)
MR Orbit + Screening Brain CT Orbit + Screening Brain (c)
Examination under Anaesthesia
In extra-ocular disease or optic nerve
involvement: B/L Bone Marrow biopsy, CSF
cytology
Nasopharyngeal Carcinoma CT scan of head and neck and chest MRI head and neck,
Bone scan for staging
Biopsy of mass or cervical lymph node FDG PET
Pure tone Audiometry (b)

NCG PHL AND PST 2020 45