MANAGEMENT OF

RHABDOMYOSARCO
MA
PRESENTER: Dr MANAS DUBEY
MODERATOR: Dr RAKESH DHANKHAR

Department of Radiotherapy, Pt. B.D.Sharma PGIMS, Rohtak

 Introduction
 Rhabdomyosarcoma is broadly classified as one
of the small, round, blue cell malignancies of
childhood.
 Rhabdomyosarcoma (RMS) is a highly
malignant soft tissue sarcoma that arises from
unsegmented, undifferentiated mesoderm or
myotome-derived skeletal muscle.
 The name is derived from the Greek
words rhabdo, which means rod shape, and
myo, which means muscle.
 3 to 4 % of all childhood cancers ( 5th most
common cancer of childhood)
 EPIDEMIOLOGY AND RISK
FACTORS
 Soft tissue sarcomas account for
approximately 7% of all pediatric cancers.
 RMS : 40 % of this group
 Non-rhabdomyosarcoma soft tissue sarcomas
(NR-STS) comprise the remainder.
 RMS is the most common of the childhood
soft tissue sarcomas, with an annual
incidence of 4.4 per 1 million whites and 1.3
per 1 million blacks.
 Male : female- 1.5
 EPIDEMIOLOGY AND RISK
FACTORS
 Majority of patients are <10 years of age at the
time of diagnosis.
 Two peak age frequencies, at ages 2 to 6 and

in adolescence.
 Age <1 year and >10 years have inferior

survival.
 Adults with RMS have been reported to have

poor outcomes. ( adult RMS 2 to 5 % of all

STS )
 Risk factors
 Cause of RMS is unknown.

 Associated with several environmental

exposures including paternal cigarette use,
prenatal x-ray exposure, and maternal drug use.

 RMS is associated with syndromes like Li-

Fraumeni syndrome, Beckwith-Wiedemann
syndrome, Costello syndrome, Gorlin basal cell
nevus syndrome.
 * In children.

SITES DISTRIBUTION*
Genitourinary( bladder and prostate- m/c, 31%
gynecologic tumors, paratesticular tumors)

Head & Parameningial (nasopharynx, 25%

Neck nasal cavity, paranasal sinuses,
middle ear, pterygopalatine
fossa, and infratemporal fossa )
Non Parameningial (scalp, 7%
parotid, oral cavity, larynx,
oropharynx, and cheek)
Extremity 13%

Orbit 9%

Retroperitoneal 7%

Trunk 5%

Other sites 3%
Natural History and Pattern of
spread

 Local spread along fascial or muscle planes

 Lymphatic spread (overall risk of regional lymphatic

spread is approximately 15% )
 Hematogenous spread are detected at the
time of presentation in approximately 15% of
patients
 most common sites of hematogenous
dissemination are lungs, bone marrow, bone.
 CLINICAL SYMPTOMS

 RMS usually manifests as an expanding mass

 Depend on the location of the tumor
 Typical presentations by the location of
nonmetastatic disease are as follows:
•Orbit - Proptosis or dysconjugate gaze
•Paratesticular - Painless scrotal mass
•Prostate - Bladder or bowel difficulties
•Uterus, cervix, bladder - Menorrhagia or metrorrhagia
•Vagina - Protruding polypoid mass (botryoid, meaning a grapelike
cluster)
•Extremity - Painless mass
•Parameningeal (ear, mastoid, nasal cavity, paranasal sinuses,
infratemporal fossa, pterygopalatine fossa) - Upper respiratory
symptoms or pain
Contd…..
 CLINICAL SYMPTOMS
 If metastatic disease is present, symptoms
of bone pain, respiratory difficulty (secondary
to lung nodules or to pleural effusion), anemia,
thrombocytopenia, and neutropenia may be
present.
 Disseminated rhabdomyoblasts in the bone
marrow may mimic leukemia, both in
symptoms and light microscopic findings
Differentials
Diagnostic Workup
CONTD….
 The following tests are indicated in RMS:
 CBC count: Anemia may be present because of
inflammation, or pancytopenia may be present from bone
marrow involvement.
 Liver function tests : Metastatic disease of the liver may
affect values of these proteins. Liver function must be
assessed before chemotherapy.
 Renal function tests: including measurements of BUN and
creatinine levels: Renal function must be assessed before
chemotherapy.
 Urinalysis (UA): Hematuria may indicate involvement of the
genitourinary (GU) tract.
 Blood electrolyte and chemistry, including evaluation of
sodium, potassium, chlorine, carbon dioxide, calcium,
phosphorous, and albumin values: Assess for abnormalities
before chemotherapy
 CONTD………..
 Tumour biopsy : necessary to make a diagnosis
and to determine what treatment should be
chosen.
 Incisional biopsy, excisional biopsy, percutaneous
needle biopsy
 Immunohistochemical staining can include positivity
for MyoD, S 100 and SMA, desmin, vimentin
 Bone marrow aspiration & biopsy : to
determine tumour cells in the bone marrow
 Cerebrospinal fluid examination should be
reserved for those patients who present with
parameningeal primaries
CONTD….
 Cytogenetics, fluorescent in situ
hybridization (FISH)
 determining the translocations t(1;13) or t(2;13),
which are associated with the alveolar subtype,
are present.
 FISH also helps in the diagnosis to assess for
break-apart of the FKHR gene.
 Reverse transcriptase–polymerase chain
reaction (RT-PCR) testing
 To assess for the characteristic translocations
associated with alveolar rhabdomyosarcoma
(ARMS) and other small, round blue-cell tumors
of childhood.
 CONTD…………..
IMAGING STUDIES
 X-RAY
 ULTRASONOGRAPHY
 MRI
 CT SCAN
 PET SCAN
 IMAGES
 Plain film
 Radiography of the primary site and of the chest
is helpful in determining the presence of
calcifications and bone involvement of the primary
tumor and to search for metastatic lung lesions.
 When present in the extremities in
children, embryonal rhabdomyosarcomas may
cause bowing of the adjacent long bones.
 IMAGES
 Ultrasound
 heterogeneous well-defined irregular mass of low
to medium echogenicity.
 Mainly for pelvic

Sites.
 CT SCAN
 Obtain a chest CT scan to evaluate for
metastases to the lungs. Chest CT scanning is
best performed before surgery to avoid
atelectasis, which can be confused with
metastasis.
 adjacent bony destruction seen in over 20% of
cases.
Ct scan ….

Coronal ( A) and axial ( B, C) scan show a

well circumscribed , homogenous mass in
the left ethmoid sinus with extension in to
the orbit and compression of left medial
rectus muscle. The tumor shows marked
MRI
 Signal characteristics include:
 T1
 low to intermediate intensity, isointense to
adjacent muscle
 areas of haemorrhage are common in alveolar
and pleomorphic subtypes
 T2
 hyperintense
 prominent flow voids may be seen particularly in
extremity lesions
 T1 C+ (Gd): shows considerable
enhancement
Contd….

 MRI improves definition of the

mass and its invasion of adjacent
organs, especially in orbital,
paraspinal, or parameningeal
regions. Obtain an MRI of the
head if the patient is symptomatic
at diagnosis.
 MRI….

RMS in left ethmoidal sinus with low signal intensity on T1 images (

A,B) and moderate enhancement on enhanced scan ( C). On a T2
image the lesion is isotense to hyperintense extraocular muscles and
WHOLE BODY MRI

testicular rhabdomyosarcoma.
STAGING SYSTEMS

New protocols for children with

soft tissue sarcoma are developed
by the Soft Tissue Sarcoma
Committee of the COG (COG-STS).
 Staging of rhabdomyosarcoma

using Current COG-STS protocols

for RMS is relatively complex.
Contd ….
 The process includes the following steps:
 Assigning a stage (consider site, size,
Surgico-pathologic Group, and
presence/absence of metastases).
 Assigning a local tumor Surgico-pathologic
Group (status postsurgical resection/biopsy,
with pathologic assessment of the tumor
margin).
 Assigning a Risk Group (classified by Stage,
Group, and histology).
 Pretreatment Staging of Rhabdomyosarcoma (
Children’s Oncology Group-Soft Tissue Sarcoma
Committee System)
Distant
Sites of Primary RegionalLymph
Stage T Stage Tumor Size Metastasi
Tumor Nodes
s
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

Favorable site = Orbit; nonparameningeal head and neck; genitourinary tract

excluding kidney, bladder, and prostate; biliary tract.
Unfavorable site = Any site other than favorable.
T1 = Tumor confined to anatomic site of origin.
T2 = Tumor extension and/or fixation to surrounding tissue.
M0 = absence of metastatic spread; M1 = presence of metastatic spread beyond
the primary site; N0 = absence of nodal spread; N1 = presence of nodal spread
beyond the primary site; X = unknown N status.
CONTD…

 THREE YEAR FAILUR FREE

SURVIVALS :
 STAGE 1 : 86%
 STAGE 2 : 80%
 STAGE 3 : 68%
 STAGE 4 : 25%
 Surgico-pathologic Group
(Children’s Oncology Group-Soft Tissue Sarcoma Committee
System)

Group Definition
I A localized tumor that is completely
(Approximately 13% of all patients are in removed with pathologically clear margins
this group.) and no regional lymph node involvement.
II A localized tumor that is grossly removed
(Approximately 20% of all patients are in with (a) microscopic disease at the
this group.) margin, (b) involved, grossly removed
regional lymph nodes, or (c) both (a) and
(b).
III A localized tumor with gross residual
(Approximately 48% of all patients are in disease after incomplete removal or
this group.) biopsy only.
IV Distant metastases are present at
(Approximately 18% of all patients are in diagnosis.
this group.)
 PATHOLOGICAL
CLASSIFICATION
PATHOLOGICAL SUBTYPE COMMENT
Superior prognosis 5-year survival rate of 88% to 95%
a) Botryoid rhabdomyosarcoma Botryoid tumors are usually noninvasive and
b) Spindle cell rhabdomyosarcoma localized and occur in mucosal-lined organs such as
the vagina, urinary bladder, middle ear, biliary tree,
and nasopharynx
Spindle cell subtype found in paratesticular sites.
Intermediate prognosis 83% failure-free survival at 3 years
a) Embryonal rhabdomyosarcoma found most commonly in the orbit, head and neck,
and genitourinary sites.
Poor prognosis •projected 3-year failure-free survival for
a) Alveolar rhabdomyosarcoma children with the alveolar subtype is 66%
b) Undifferentiated sarcoma And patients with undifferentiated sarcoma is 55%.
c) Anaplastic rhabdomyosarcoma
Subtypes whose prognosis is not
presently evaluable
a. Rhabdomyosarcoma with rhabdoid
features
Note: Pleomorphic type is extremely rare; and treated like SOFT
TISSUE SARCOMA
Contd….
PROGNOSTIC FACTORS

 AGE ( 1 to 9 yr – good
prognosis )
 SITE

 EXTENT OF DISAESE

 PATHOLOGIC
CHARACTERISTIC
CONTD……

Favourable sites.

unfavourable
sites.
 MANAGEMENT

 All children with RMS require

multimodality therapy with
systemic chemotherapy, in
conjunction with either surgery,
radiation therapy (RT), or both
modalities for local tumor control and
should be referred (at least initially)
to a center with personnel who are
skilled in caring for children with
Contd….
 The treatment of rhabdomyosarcoma by the
Children's Oncology Group and in
Europe—as exemplified by trials from the
Intergroup Rhabdomyosarcoma Study
Group (IRSG), the Children's Oncology
Group Soft Tissue Sarcoma Committee
(COG-STS), and the International Society of
Pediatric Oncology Malignant
Mesenchymal Tumor (MMT)
Contd….
Reevaluation :
clinical
examination, CT
and MRI to know
the extent of the
tumor
 SURGERY

 The basic principle for the initial

surgical treatment of children with
RMS is complete resection of the
primary tumor with a surrounding
margin of normal tissue, along with
sampling lymph nodes in the draining
nodal basin, provided that major
functional/cosmetic impairment will
not result.
 SURGERY
 Current trend: less surgical role and more
reliance on radiation and chemotherapy
 Major goal- preservation of function
 Complete resection possible in only 20% of
patients
 Resection with microscopic residual
disease in 20% of patients.
 Only biopsy in rest of the 60% of patients.
surgery (contd….)
 Suspected RMS : INCISIONAL BIOPSY
 Excision is indicated if it can be done
without compromise of function or
cosmesis.
 For complete resection 5mm margin
required.
 If microscopic disease remains : primary
rexcision can be considered
 Surgical treatment result shows 20%
survival rate ( before multimodality era)
 Surgery contd…..

Longitudina
l incision

Important to evaluate the lymphatics in all children with

RMS, best performed at the time of the initial procedure
Sentinel node biopsy
The sentinel node should be blue and should have high
Proper orientation of the counts of radioactive tracer signal when checked with the
biopsy allows complete gamma probe.
resection at second
operation.
Contd….
 Second look operations (SLO): delayed
exicison , useful for converting partial
response to complete response after CT.
 Improve survival
 Only select sites are appropriate: bladder,
extremity, trunk.
 In the IRS-III study, 28% of patients having
clinical partial response and 43% having no
response to induction chemotherapy were
reclassified as having pathologic complete
response after second-look operation
RESULTS

GRD : gross residual disease, MR :

microscopic residual, CR: complete
resection
CHEMOTHERAPY
 Chemotherapy is necessary in all cases.
 Single agents and combination
chemotherapy used
Single agent Response rate
Vincristine 59%
Dactinomycin 24%
Cyclophsophamide 54%
Cisplatin 21%
Dacarbazine 11%
Mitomycin-c 36%
Topotecan 46%
Contd…
 Combination chemotherapy
 VAC(Vincristine, Dactinomycin,
Cyclophosphamide) – gold standard regimen :
(increased survival in patients with
localized disease to approximately 60%)
 VAdriaC Alternating with Ifosfamide & Etoposide

 VAC Alternating With Vincristine, Topotecan, and

Cyclophosphamide
The intensity and duration of the chemotherapy
are dependent on the Risk Group assignment
 CONTD…. ( standard combination
chemotherapy)
CHEMOTHERAPY DOSE AND SCHEDULE COMMENTS

Vincristine 2 mg/m2 D1 & D8 Total duration = 2yrs

VAC Cyclophosphamide Pulses 275-330
mg/m2 daily for 7 days 6 weekly
with vincrstine
Dactinomycin Total Dose 2-2.5
mg/m2 divided daily injections
over 5 -7 days (0.5 mg/m2 daily)
every 3 months x 5 courses

VAdriaC Vincristine 1.5 mg/m 2 weekly x 3 Chemotherapy cycles alternated

for first 2 cycles ---- then on D1 every 3 weeks for 39 weeks
ALTERNATING WITH only
IFOSFAMIDE AND Doxorubicin 60 -75 mg /m2 IV
ETOPOSIDE 48 hours continuous infusion
Cyclophosphamide 600 mg/m2
DAILY FOR 2 DAYS with Mesna
After 3 weeks Ifosfamide 1.8
gm/m2 IV daily for 5 days
+Mesna, Etoposide 100 mg/m2
daily for 5 days

Handbook of Cancer Chemotherapy 8th Ed. Year 2011 Roland T.Skeel Samir
N.Khleif
Contd….
 Low-risk patients :
 Standard treatment options- Certain subgroups of
low-risk patients have achieved survival rates higher than 90%
by undergoing two-drug chemotherapy with vincristine and
dactinomycin (VA) plus RT for residual tumor.
 Characteristics of Low-Risk Patients with High Survival
Rates Using Two-Drug Therapy with VA ± RT
(5-year overall FFS rate = 88% 5-year OS rate = 97% COG-D9602 Study )

Site Size Group Nodes

Favorable Any I, IIA N0
Orbital Any I, III N0
Unfavorable ≤5 cm I, IIA N0
 Contd…
 Other subgroups of low-risk patients have achieved
survival rates higher than 90% by undergoing three-
drug chemotherapy with VA and cyclophosphamide
(VAC) plus RT for residual tumor. The total
cyclophosphamide dose used in completed COG
protocols was 28.6 g/m2
Characteristics of Low-Risk Patients with High Survival Rates Using
Three-Drug Therapy with VAC ± RT
(5-year overall FFS rate = 85% 5-year OS rate = 93% COG-D9602 Study)

Site Size Group Nodes

Favorable (orbital Any IIB, IIC, III N0, N1
or non-orbital)
Unfavorable ≤5 cm II N0
Unfavorable >5 cm I, II N0, N1
 Intermediate-risk patients :  High-risk patients
 vincristine, dactinomycin,  Metastatic disease in one or
more sites at diagnosis
and cyclophosphamide (stage IV). These patients
(VAC) is the standard continue to have a relatively
poor prognosis (5-year
chemotherapy treatment. survival rate of 50% or
lower) with current therapy,
 Intermediate-risk patients and new approaches to
have survival rates treatment are needed to
improve survival in this
ranging from 55% to 70%. group. The standard
systemic therapy for
 (IRS STUDY-IV 1991-1997)
children with metastatic
RMS is the three-drug
combination of VAC
 RADIOTHERAPY
 External Beam RT is an effective method for
achieving local control of tumor for patients
with microscopic or gross residual disease
following biopsy, initial surgical resection, or
chemotherapy
 50 to 65 Gy was thought to be necessary to
achieve local control of the primary tumor
regardless of the nature of the surgical
procedure.
 IRS I-IV studies have demonstrated
reduction in RT doses with better results in
RADIOTHERAPY
 The role of RT is to eradicate microscopic
disease present after resection, treat gross
disease, and consolidate visible sites of
metastatic involvement.
CONTD…
 Presently RT is indicated for Group I
patients with alveolar or undifferentiated
histology, all Group II & III patients.

 RT is not required in Group I completely

resected with embryonal histology
RESULTS….
 The treatment of completely resected disease
(group I) come from review of prior IRSG trials I to
III demonstrating improvement in FFS and OS for
patients with ARMS when RT is delivered (73%
vs. 44% and 82% vs. 52%, respectively)
 Patients with group II disease received adjuvant

radiation, resulting in local failure rates of less

than 10%.
 Patients with group III disease have local failure
rates of 10% to 15%.
 RMS…RADIOTHERAPY…..
53

•Treatment Portals designed to encompass involved region

(pre CT) with margins encompassing Sx sites and biopsy tracts
•Target Volumes
•GTV =Tumor seen at time of initial diagnosis
•CTV = 1cm margins added to GTV
•PTV = 5 mm margins added to CTV
•No prophylactic LN RT on clinically –ve findings in pts
having combination CT
•If Clinically suspicious L.Nodes = LN Biopsy /LN included
in RT Portal
RMS…..RADIOTHERAPY
TECHNIQUES TO DELIVER RADIATION
• Conventional RT
• 3D- CRT
• IMRT –more target coverage than CRT but No difference in
Local Failure Rate & Survival
• Proton Beam RT- can spare more normal tissue adjacent to
• targeted volume than IMRT
• Intracavitary /Interstitial Brachytherapy in selected sites –
• primary Rx / boost(vagina/vulva/bladder/prostate)
• Early RT in high risk patients may provide better Tumor control
& survival
 RMS…..RADIOTHERAPY ….
55

• Timing of RT =
• generally 1 to 3 months after chemotherapy initiation

• RT is usually given over 5 to 6 weeks

•Control of microscopic or gross residual disease

•CT + RT  LOCAL CONTROL

92% group II
80% group III
CONTD….
 Individual sites
Sites Management and results

ORBIT : Favorable prognostic site Primary treatment =RT + CT ( VAC)

> 90% Cure Rate
Histology >90% Embryonal
Local RT = between 3rd & 12th week of
Treatment , ( Dose= 45Gy)

•Nonorbital Parameningeal : (VAC) CT and RT essential for maximizing chances

of cure
41% of these patients → invading base of the
Whole-brain irradiation =not necessary
skull
If Meningeal dissemination – Craniospinal RT
•35% of these patients → meningeal extension
RT dose =50.4 Gy/ 28 fractions
5 year survival = 75% with adequate RT
Local RT = Irradiation of primary tumor + adjacent
meninges
 CONTD….
SITES MANAGEMENT AND RESULTS

Non-orbital Non- more amenable to complete gross surgical

excision
parameningeal : RT = based on amount of residual Tumor after
surgery
5-year failure-free survival in IRS-IV = 80%

Extremity : Commonly Alveolar / Complete Surgical excision difficult to achieve

Undifferentiated type
Large, Deeply invasive
RT and Multiagent CT= excellent local control
Avoid disfiguring and mutilating surgical
procedures
Limb-salvage procedures including RT & CT
Overall survival 3 yr – 70%
FFS 55%
 Contd…
PELVIC SITES MANAGEMENT AND RESULTS

Bladder And Prostate IRS III  Intensive Regimen

 Multiple agents (VAC + doxorubicin +
cisplatin ) plus RT after 6 weeks of start of
treatment plus Second-look surgery
5 year survival 82%
Functional bladder 64%

•Paratesticular: 7% of all RMS Complete resection – high inguinal

orchidectomy

• Painless scrotal or inguinal mass Ipsilateral RPNSLND for all children 10

years or above (High risk LN involment)
Regional LN RT to periaortic & ipsilateral
iliac nodes (If LN mets +)
5 Year Survival : 1) 69% in Nodal mets,
 2) 96% in NO nodal mets
 CONTD…..
 PELVIC SITES: ( gynecologic sites) 4% of all RMS
 one third of all pelvic RMS
 Site :Vulva ,Vagina (Most Common in this Gp),Cervix, Uterus
 VAGINA RMS : Surgical resection with chemotherapy
Post op Radiotherapy – Current COG STS committee guidelines on postsurgical
microscopic or macroscopic tumor positivity
 UTERINE/CERVICAL/ VULVAR RMS :
 Surgery F/b CT & RT based on tumor present after initial surgery
 Intracavitary and interstitial brachytherapy are useful in selected pts

 5-year survival in 1 to 9 years Children = 98%

 5-year survival in infants & adolescents= 90%
 BULLET POINTS…..
 A highly malignant soft tissue sarcoma that arises from
unsegmented, undifferentiated mesoderm or myotome-
derived skeletal muscle
 Most common soft-tissue sarcoma of childhood
 RMS majority Embryonal & Alveolar RMS
 Multimodality treament
 CT necessary for all cases
 5-year survival has increased from IRS-I to IRS-V and
toxicities minimized
BIBLIOGRAPHY
 DEVITA 10TH EDITION , 2015
 PEREZ 6TH EDITION , 2013
 .

 .
THANK YOU
Contd….
IRSG YEARS
IRSG - I 1972 - 1978

IRSG - II 1978-1984

IRSG-III 1984-1991

IRSG-IV 1991-1997

IRSG-V 1997-2002