Rhabdomyosarcoma is a rare type of soft tissue sarcoma that develops from skeletal muscle cells. It is most common in children and adolescents. There are two main histologic subtypes - embryonal RMS, which is more common and has a better prognosis, and alveolar RMS, which occurs in older patients and has a worse prognosis. Treatment involves surgical resection of the primary tumor along with chemotherapy and radiation. Accurate staging is important for determining prognosis and selecting the appropriate treatment protocol. The goal of surgery is a wide excision of the tumor with clear margins followed by lymph node sampling or dissection depending on tumor characteristics and location.

1. Rhabdomyosarcoma
Dr T Sasidhar
Moderator: Dr Rajesh MS MCh

2. Introduction
• Rhabdomyosarcoma was first described by Weber, a
German physician, in 1845.
• RMS was formally classified in 1946 by Arthur Stout.
• Historically, the mainstay of therapy for rhabdomyosarcoma
(RMS) has been aggressive surgical resection with a survival
rate of 7 -70%.
• chemotherapy in 1961.
• Radiotherapy 1965.
• establishment of the Intergroup Rhabdomyosarcoma Study
Group (IRSG) in 1972.
• goal of the IRSG was to oversee the development of
treatment protocols for RMS

3. Demographics
• most common type of soft tissue sarcoma diagnosed
during the first 2 decades.
• Accounting for 4.5% of all cases of childhood cancer
• Third most common extracranial solid tumor of
childhood after Wilms’ tumor and neuroblastoma.
• bimodal distribution,
– 2 and 6 years and
– 10 and 18 years of age.
• Males> females (58.4% vs 41.6%), whites >african
americans

4. Tumor Biology
• malignant tumor of mesenchymal origin
• RMS also falls under the greater category of
small, blue, round-cell tumors of childhood
that includes “neuroblastoma, lymphoma, and
primitive neuroectodermal tumors (PNET)”.
• two major histologic subtypes of RMS are
embryonal and alveolar.

5. small, blue, round-cell tumor RMS

6. Embryonal RMS (ERMS):
• the most common type of RMS, affecting two thirds of all patients.
• younger patients
• more frequently in the head and neck region as compared with the
extremities.
• further broken down into spindle-cell and botryoid subtypes.
• ERMS is typically composed of spindle shaped cells with a rich
stroma.
• ERMS has a favorable survival rate of 60%.
• Spindle-cell histology is common in paratesticular lesions
• botryoid lesions are generally polypoid masses filling the lumen of
hollow viscus.

7. Spindle-cell histology

8. Alveolar RMS (ARMS):
• older children
• most commonly located on the trunk or extremities.
• These lesions are composed of small, round, densely
packed cells arranged around spaces resembling
pulmonary alveoli.
• this histologic classification of RMS may, in the near
future, be supplanted by gene array analysis.
• Prognosis is worse in ARMS than ERMS.
• 5-year survival rate of 54%.

9. Alveolar RMS

10. • For all histologic types of RMS, outcome is
heavily dependent on
– age at diagnosis,
– the primary anatomic site,
– extent of disease (tumor size, invasion, nodal
status, metastatic disease), and
– the completeness of surgical excision

11. Genetics
• exact nature of the pathogenesis of RMS is unclear;
however, many hypotheses exist.
• “largely thought that RMS arises as a consequence of
regulatory disruption of skeletal muscle progenitor cell
growth and differentiation”.
• Pathogenic roles have been suggested for the MET
protooncogene, and the TP53 proto-oncogene.
• MET protooncogene is involved in migration of
myogenic precursor cells.
• TP53 proto-oncogene is responsible for tumor
suppression
largely thought that RMS arises as a consequence of regulatory disruption of
skeletal muscle progenitor cell growth and differentiation”.

12. • At the chromosomal level, ERMS is characterized
by a loss of heterozygosity at the 11p15 locus,
with a loss of maternal information and
duplication of paternal genetic information.
• Within this locus lies the insulin growth factor II
(IGF-II) gene.
• Both ERMS and ARMS overproduce IGF-II, which
has been shown to stimulate RMS tumor growth,
suggesting that IGF-II plays a role in unregulated
growth of these tumors.

13. Although the significance is unclear, ARMS is frequently tetraploid, whereas
ERMS lesions are generally diploid.
PAX/FKHR fusions - results in increased PAX activity leading to the de-differentiation
and proliferation of myogenic cells
Understanding the role of these fusion proteins in tumor development may provide
insight into treatment strategies and potential biomarkers for the diagnosis of RMS
it has been demonstrated that approximately 25% of ARMS tumors are translocation
negative. By gene array analysis, these fusion negative ARMS tumors more closely
resemble ERMS overall and have a similar prognosis to ERMS
It has therefore been proposed that tumors should be divided into PAX/FKHR fusion–
positive and –negative tumors rather than the more ambiguous alveolar and
embryonal histologies

14. • most cases of RMS occur sporadically.
• The disease is associated with familial syndromes,
including Li-Fraumeni and neurofibromatosis I.
• Gorlin syndrome –
– is an autosomal dominant disorder caused by
mutations in the PTCH tumor suppressor gene
mapping to chromosome 9q22.3.
– Animals with mutations in the PTCH gene have
elevated levels of the tumor growth–promoting IGF-II
and develop spontaneous RMS.

16. Presentation of Rhabdomyosarcoma
• asymptomatic mass
• Specific symptoms vary based on the site of
occurrence and extent of disease - Specific
symptoms vary based on the site of occurrence
and extent of disease.
• generally related to mass effect or complications
of the tumor.
• most common sites of primary disease are the
head and neck region, the genitourinary tract,
and the extremities.

17. Preoperative Workup
• Standard lab work
• Imaging workup
• Metastatic workup

18. Standard lab work
– complete blood counts (CBC),
– electrolytes,
– renal function tests,
– liver function tests (LFTs), and
– urinalysis (UA)

19. Imaging workup
– CT, MRI
– CT is advantageous for the evaluation of bone erosion and
abdominal adenopathy
– MRI provides better definition of the tumor and surrounding
structures.
– MRI is preferable for limb, pelvic, and paraspinal lesions.
• Tumor imaging defines the proximity of tumors to vital
structures and determines size.
• Both factors are important when determining if the tumor
can be primarily resected or if neoadjuvant therapy is
required to decrease tumor size and thereby decrease the
morbidity of resection

20. Metastatic workup:
– includes a bone marrow aspirate and bone scan,
CT of the brain, lungs, and liver, and lumbar
puncture for cerebrospinal fluid collection.
– Recent evidence would suggest that tumor
volume and patient weight may be superior
predictors of failure-free survival than tumor
diameter and patient age in patients with
intermediate-risk RMS

21. Metabolic imaging using 18-FDG PET:
– widely used in the adult population to determine the
extent of disease
– there is limited experience in the pediatric population.
– would be both a sensitive and specific tool in the
clinical determination of the extent of disease.
– when combined with CT, it may be more accurate than
conventional imaging modalities in staging patients or
re-staging patients at the time of recurrence.

22. • Accurate diagnosis is usually accomplished through
immunohistochemical staining for muscle-specific
proteins such as myogenin, muscle specific actin,
desmin, D-myosin, and myoD1.
• Myogenin, in particular, has been shown to be highly
specific to RMS
• The alveolar type of RMS tends to have stronger
muscle-specific protein staining. Electron microscopy
may also aid in diagnosis, with the presence of actin
and myosin or Z bands pointing to a positive diagnosis
of RMS

24. Pretreatment Clinical Staging
• Staging of RMS is determined by
– the site of the primary tumor,
– primary tumor size,
– degree of tumor invasion,
– nodal status, and
– the presence or absence of metastases
• it is based solely on the preoperative workup
of imaging and physical examination

26. Surgical Principles
BIOPSY:
– Open biopsy of a mass suspected to be RMS should be
performed to confirm the diagnosis
– For small lesions in areas that will be treated with
chemotherapy and radiation or for metastatic disease,
core needle biopsy may be appropriate.
– Image guidance may increase the accuracy of sampling.
– Clinical and radiographic positive lymph nodes should be
confirmed pathologically. Open biopsy is recommended
– Sentinel node biopsy may offer a safe and less invasive
means of lymph node evaluation for extremity and truncal
lesions

27. RESECTION OF THE MASS
• Surgical biopsy of a primary lesion is often
performed prior to a definitive surgical resection.
• If this is the case, pretreatment reexcision (PRE) is
advisable.
• PRE is a wide reexcision of the previous operative
site with adequate margins of normal tissue prior
to the initiation of adjuvant therapy.
• PRE is most commonly performed on extremity
and trunk lesions but should be considered the
treatment of choice whenever technically
feasible.

28. • The primary goal of surgical intervention is wide and
complete resection of the primary tumor with a
surrounding rim of normal tissue.
• A circumferential margin of 0.5 cm is considered
adequate.
• All margins should be marked and oriented at the
operative field to enable precise evaluation of margins.
• If a narrow margin occurs, several separate biopsies of
“normal” tissue around the resection margin should be
obtained. These specimens should be marked and
submitted separately for pathologic review

29. • Communication between the pathologist and
surgeon is mandatory to ensure that all margins
are accurately examined.
• The surgeon should not bisect or cut the excised
tumor into specimens prior to sending it to the
pathologist.
• Any microscopic or gross tumor should be
marked with small titanium clips in the tumor
bed to aid radiotherapy simulation and
subsequent reexcision.

30. LYMPH NODE SAMPLING/DISSECTION
• Lymph node status is an important part of
pretreatment staging and therefore directly impacts
risk-based treatment strategies in RMS.
• Regional lymph node disease (N-1) has been identified
in ARMS as an independent poor prognostic factor in
stage 3 patients.
• N-1 disease alters both failure-free survival (FFS) and
over all survival (OS) for ARMS but not ERMS.
• For patients with N-1, ARMS outcomes were more
similar to patients with single- site metastatic disease
than those with only local disease.

31. • For ERMS other prognostic factors, such as patient age,
tumor invasion (T stage), site of primary tumor, and the
presence of metastasis at initial presentation, were
more important prognostic factors than N-1 disease.
• Lymph node removal has no therapeutic benefit,
therefore prophylactic lymph node resection plays no
role in therapy.
• Therefore clinical and/or radiographic negative nodes
do not require pathologic evaluation except in
extremity tumors and for children older than 10 years
of age with paratesticular tumors.

32. • In both of these sites, the high incidence of nodal disease
and false-negative imaging necessitates pathologic
evaluation of regional nodal basins.
• For childhood RMS, sentinel node mapping is not yet the
standard of care but may prove to be effective.
• If regional nodes are positive then distant nodes should be
harvested for pathologic evaluation.
• For upper extremity lesions, the distant nodes would be the
ipsilateral supraclavicular (scalene) nodes.
• In the lower extremity, the distant nodes would include the
iliac and/or paraaortic nodes.
• For paratesticular RMS, the ipsilateral paraaortic lymph
nodes above the renal vein are considered distant nodes.

34. CLINICAL GROUP
• The extent of residual disease after resection is one of
the most important prognostic factors in RMS.
• For this reason, a clinical grouping system was
developed in 1972 to stratify patients into groups that
would more accurately reflect their prognosis and
treatment options.
• Currently, patients are assigned to a clinical group
based on the completeness of tumor excision and the
evidence of tumor metastasis to the lymph nodes or
distant organs after pathologic examination of
surgical specimens.

35. This system differs from TNM staging in that determination of each patient’s
clinical group is based on the extent of the surgical resection instead of tumor
size and site
One criticism of clinical grouping is that variation of surgical techniques make
comparisons of clinical grouping between different institutions problematic.

36. SECOND-LOOK OPERATIONS AND
AGGRESSIVE RESECTION FOR RECURRENCE
• After completing adjuvant therapy, patients with RMS are reimaged
with CT or MRI.
• If residual tumor remains, or if the outcome of therapy remains in
doubt, a second-look operation (SLO) may be considered.
• the goal of SLO is complete resection of disease.
• In general, an aggressive surgical approach is used for recurrent
RMS.
• However, resection of residual masses after completion of adjuvant
therapy may not be warranted. Associated morbidity of resection
and the inability to achieve complete resection in some cases need
to be considered
• IRS-III suggested that SLO results in the reclassification of 75% of
partial responders to complete responders after excision of residual
tumors.

37. Chemotherapy
• combination of vincristine, actinomycin-D, and
cyclophosphamide (VAC).
• The combination of ifosfamide and etoposide was
tested in a Phase II therapy window in IRS-IV.
• When combined with VAC, ifosfamide, and
etoposide therapy resulted in a better 3-year
survival rate, with less bone marrow toxicity
when compared with the use of vincristine and
melphalan with standard VAC regimens.

38. • Other regimns: doxorubicin and the
topoisomerase inhibitor irinotecan.
• Irinotecan is of little value as a single agent
but useful adjunct in combination therapy.
• topotecan has shown some promise in
patients with stage 4 disease when combined
with cyclophosphamide.

39. Radiation Therapy
• important adjunct to therapy, offering improved
local control and outcomes.
• Candidates for radiotherapy primarily include
those with group II (microscopic residual disease)
or group III (gross residual disease) disease.
• Group II disease - low-dose radiation (40 Gy at
1.5 to 1.8 Gy/fraction) is associated with local
tumor control rates of at least 90%.
• For patients with group III disease, radiation
doses are more commonly 50 Gy.

40. • IRS-IV protocol demonstrated that twice-daily
irradiation at 110 cGY per dose, 6 to 8 hours apart
(hyperfractionated schedule) for 5 days per week is
feasible and safe.
• Difficult to accomplish in small children who require
twice-daily sedation for treatment.
• Unfortunately, demonstrated no improvement in local
control over conventional radiation therapy.
• Modern techniques, such as intensity modulated
radiation therapy (IMRT) and proton beams, may
improve outcome without compromising long-term
function.

41. Assessment of Response to Treatment
• European RMS trials have incorporated the use of
conventional radiologic modalities to evaluate
the response to induction therapy.
• IRS-IV data demonstrated no predictive value of
radiographic response after 8 weeks of induction
therapy.
• the significance of persistent radiographic masses
in patients treated for RMS is unknown.
• It is possible that FDG PET may offer useful
clinical information in patients treated or partially
treated for RMS.

42. SPECIFIC ANATOMIC SITES
• Tumors in different parts of the body may
behave differently than those in other areas.
• some areas of the body offer unique obstacles
to surgical resection.

43. Head and Neck (Superficial
Nonparameningeal)
• Approximately 35% of RMS arises, 75% - orbit
• The histologic variant of RMS correlates to some extent
with the location of the orbital tumor.
• ERMS and differentiated types more commonly arise in
the superior nasal quadrants, whereas ARMS generally
originate within the inferior orbit.
• Biopsy  resection
• Resection may be limited by the inability to obtain an
adequate margin.
• Lymph nodes are rarely involved. Orbital RMS carries
the best prognosis. Outcomes correlate strongly with
tumor location.

45. Parameningeal Sites
• tumors arising in the middle ear/ mastoid, nasal cavity,
parapharyngeal space, paranasal sinuses, or the
pterygopalatine/infratemporal fossa region.
• considered high risk because of their propensity to
cause cranial nerve palsy, bony erosion of the cranial
base, and intracranial extension.
• Wide local excision is recommended but is often not
feasible.
• The recognition of poor outcomes associated with
meningeal extension has lead to a propensity for early
radiation therapy of primary tumors and adjuvant
chemotherapy.

46. Trunk
• 4% to 7% of tumors
• associated with a poor prognosis
• Symptoms for RMS of the trunk often occur
late in the progression of disease, which leads
to late diagnoses.
• Complete surgical resection is difficult,
particularly when the pleura and peritoneum
are involved.

47. • resections are frequently morbid and associated with
poor cosmetic outcomes.
• Resection may necessitate major chest wall or
abdominal wall reconstruction with prosthetic
materials or with flaps.
• Indicators of poor prognosis:
– advanced stage at presentation,
– alveolar histology,
– recurrence disease,
– tumor size greater than 5 cm,
– lymph node involvement, and the
– inability to undergo gross total resection

48. Abdominal Wall
• painless, firm mass.
• can be removed completely at presentation or
following neoadjuvant chemotherapy.
• However, tumors arising from the interior abdominal
wall may not be noticed until late.
• Tumor excision should include full-thickness resection
of the abdominal wall, including the skin and
peritoneum with a margin of normal tissue.
• Reconstruction of the abdominal wall can be
performed with mesh or myocutaneous muscle flaps.
• If the size or location prevents adequate excision,
neoadjuvant chemotherapy should be initiated.

50. Chest Wall
• The differential diagnosis for malignant chest wall masses
includes Ewing sarcoma, primitive neuroectodermal tumors
(PNET), and RMS.
• Wide local excision of chest wall lesions with a 2-cm
margin, including the previous biopsy site, involved chest
wall muscles and involved ribs, as well as wedge excision of
any involved underlying lung, is recommended.
• have a worse prognosis than other trunk lesions.
• radiotherapy may be beneficial for local control of tumor.
• this option is associated with significant morbidity,
including pulmonary fibrosis, decreased lung capacity,
restrictive defects from altered development of the
thoracic cavity, and scoliosis

51. Biliary Tract
• Classically, patients with biliary RMS present at a young
age (average age 3.5 years) with jaundice and
abdominal pain, often associated with abdominal
distension, vomiting, and fever.
• Workup reveals a significant direct hyperbilirubinemia
and a mild elevation of hepatic transaminases.
• Gross total resection of biliary tract RMS is rarely
possible and is often unnecessary because of good
outcomes with chemotherapy and radiation.
• Currently, open biopsy is the only definitive role of
surgery in the treatment of biliary RMS, although this is
controversial.

52. • The histology of these tumors is often the
botryoid variant of embryonal RMS, which
carries a good overall prognosis.
• Biliary obstruction can be relieved by stenting,
but external biliary drains should be avoided
because of infectious complications.
• Overall, outcomes are good unless distant
metastases are present at the time of
diagnosis

55. Paraspinal Sites
• rare (3.3% of all RMS) and carries a poor prognosis.
• These tumors tend to spread along anatomic
structures, such as neurovascular bundles and fascial
sheaths, occasionally causing spinal cord compression.
• Complete excision of paraspinal lesions is often difficult
• Recurrence rates for paraspinal RMS are high (55%)
with the majority of these occurring at distant
locations.
• The lung is the most common site of distant metastasis
followed by the central nervous system.

56. Retroperitoneum/Pelvis
• Like paraspinal tumors, retroperitoneal/pelvic
lesions are often discovered at an advanced
stage and thus generally carry a poor
prognosis.
• These tumors can envelop vital structures,
making complete surgical resection
challenging.
• Neoadjuvant chemotherapy may play a role in
tumors that cannot be safely resected

57. • With the exception of group IV metastatic disease,
aggressive resection is recommended and has been
shown to offer improvement in survival.
• Group IV patients with embryonal histology and those
who present at less than 10 years of age may also
undergo surgical debulking.
• It has been demonstrated that excising greater than
half of the tumor before chemotherapy resulted in
improved rates of failure-free survival when compared
with patients who did not undergo debulking.
• This is the only setting in which surgical debulking of
RMS has shown any benefit.

58. Perineal/Perianal Sites
• Perineal tumors are rare and usually present at an advanced stage.
• Characteristics associated with improved survival include a primary
tumor size less than 5 cm, less advanced clinical group and stage,
negative lymph node status, and age less than 10 years of age.
• Interestingly, histology does not affect overall outcome for these
tumors.
• Resection of these tumors can be challenging because of proximity
to the urethra and anorectum.
• At resection, particular care should be taken to preserve
continence.
• If anorectal obstruction exists, a temporary colostomy may be
necessary.
• Patients presenting in clinical group I had 100% overall survival at 5
years compared with 25% for group IV patients

59. Extremities
• accounts for 20% of all new diagnoses.
• majority of these tumors have alveolar histology
and thus a poor prognosis.
• Cure rate has been steadily improving from 47%
in IRS-II to 74% in IRS- III.
• complete gross resection at initial surgical
intervention is the most important predictor of
failure-free survival.
• primary goal of local tumor control in extremity
tumors is limb-sparing complete resection.

60. • Positive regional lymph nodes are found in 20% to 40%
and are associated with decreased overall survival.
• Seventeen percent of IRS-IV patients with clinically
negative nodes were found to have microscopic nodal
disease on biopsy. In light of this, surgical evaluation of
lymph nodes is necessary to accurately stage children.
• Currently, axillary sampling is recommended for upper
extremity lesions, and femoral triangle sampling is
recommended for lower-extremity lesions.

61. • Sentinel lymph node mapping may be a useful adjunct in the setting
of extremity RMS.
• If regional nodes are involved, then x-ray therapy (XRT) fields are
adjusted to incorporate regional lymph node basins.
• This approach is associated with decreasing rates of local and
regional recurrence.
• In-transit nodal involvement at the time of diagnosis, present in 4%
of IRS-IV patients, has also been identified as a factor contributing
to regional treatment failure.
• Evaluated by MRI, or possibly FDG PET, at the time of diagnosis.
• Radiation therapy (RT) should be used at regional lymph node sites
in these patients

62. Genitourinary Sites: Bladder/Prostate
• Typically presents with urinary obstructive
symptoms.
• These lesions are typically of embryonal
histology (73%).
• The major goal of surgery is complete tumor
resection with bladder salvage.
• This can be achieved in 50% to 60% of
patients. Partial cystectomy has resulted in
similar survival rates.

63. • Bladder dome tumors frequently can be
completely resected, whereas more distal
bladder lesions frequently require ureteral
reimplantation or bladder augmentation.
• Prostatic tumors require prostatectomy, often
combined with an attempt at bladder salvage
with or without ureteral reconstruction.
• Lymph nodes are involved in up to 20% of cases.
Therefore during biopsy or resection, iliac and
para-aortic nodes should be sampled, as well as
any other clinically involved nodes.

64. Genitourinary Sites:
Vulva/Vagina/Uterus
• Traditionally - aggressive resection followed by
chemotherapy with or without radiation.
• Newer treatment approaches rely more heavily on
neoadjuvant chemotherapy.
• Primary tumors of the vagina are about 5 times more
common than cervical tumors.
• The vast majority -embryonal or are of the botryoid
subtype, account for - favorable prognosis.
• respond well to chemotherapy, with impressive tumor
regression that often precludes the need for radical
operations such as pelvic exenteration.

65. • Vaginectomy and hysterectomy are performed
only for persistent or recurrent disease.
• Oophorectomy is only indicated in the setting
of direct tumor involvement.
• Prognosis for this tumor site with only
locoregional disease is excellent, with an
estimated 5-year survival of 87%

67. Paratesticular Sites
• painless scrotal mass.
• Histology is generally favorable, with most
tumors showing the spindle-cell subvariant of
embryonal histology.
• Survival rates are greater than 90% for patients
presenting with group I or II disease.
• Radical orchiectomy via an inguinal approach
with resection of the spermatic cord to the level
of the internal ring is the standard of care.

68. • Open biopsy should be avoided, because the flow
of lymphatics in this region facilitates spread of
the disease.
• If a trans scrotal biopsy/resection has been
performed, subsequent resection of the
hemiscrotum is required.
• If unprotected spillage of tumor cells occurs
during tumor resection, these patients are
considered clinical group IIa regardless of the
completeness of resection

69. • The incidence of nodal metastatic disease for paratesticular
RMS is 26% to 43%.
• Unfortunately, studies have demonstrated that CT is a poor
means of evaluating lymph node positivity in the
retroperitoneum.
• In addition, patients older than 10 years of age or those
with enlarged nodes have a much higher incidence of node
positivity.
• Those patients should therefore undergo an ipsilateral
retroperitoneal nodal resection.
• Suprarenal nodes should be evaluated, because positive
nodes in this area place a patient in group IV with
disseminated metastatic disease.

71. Metastatic Disease
• both through hematogenous and lymphatic
routes.
• Children with metastatic RMS have very poor
survival rates.
• For the IRS studies I through III, children with
metastatic disease had a 5-year disease-free
survival of 20%, 27%, and 32%, respectively.

72. • window studies” - to address potential
chemotherapeutic regimens that would improve the
disease-free survival period when given to patients
with newly diagnosed metastatic RMS.
• One such study evaluated the combination of
ifosfamide and doxorubicin for the treatment of
children with metastatic disease who are less than 10
years of age, have embryonal histology, and lack nodal,
bone, or bone marrow involvement.
• This treatment strategy increased 5-year failure-free
survival to 28% and 5-year overall survival to 34%.

73. Prognosis
Favorable prognostic factors include
1. Embryonal/ botryoid histology,
2. primary tumor sites in the orbit and non parameningeal
head/neck region and genitourinary nonbladder/prostate
regions,
3. a lack of distant metastases at diagnosis,
4. complete gross removal of tumor at the time of diagnosis,
5. tumor size less than or equal to 5 cm, and
6. age less than 10 years at the time of diagnosis
• Clinical grouping was identified as one of the most
important predictors of failed treatment and tumor relapse

74. Group II disease
Those patients in group II at highest risk for
treatment failure had
– alveolar/ undifferentiated histology,
– unfavorable primary sites,
– regional disease with residual tumor after gross
resection and
– node involvement, or were treated with early
therapeutic regimens.

75. Group III disease
Predictors of failure-free survival in group III include
1. tumor size less than 5 cm,
2. Primary sites of orbit and bladder/prostate, and
3. TNM staging equivalent to T1/N0Nx tumors in
stage I or stage II.
• Since radiotherapy is important for local control
of group III disease, the incidence of local failure
was stratified by radiotherapy dosing (<42.5 vs.
42.5 to 47.5 vs. > 47.5 Gy) and was not
significantly different among these dose ranges.

76. Metastases (group IV) disease
• 15% of RMS at the time of diagnosis.
• Poor outcome.
• Compared with patients without metastatic disease, group
IV patients in the IRS-IV study were more likely to be
– older (median age 7 years vs. 5 years),
– had a higher incidence of alveolar histology (46% vs. 22%),
– had tumors that were more invasive (T2: 91% vs. 49%) and
larger (>5 cm: 82% vs. 51%),
– a higher incidence of lymph node involvement (N1: 57% vs.
16%), and
– had a greater proportion of extremity and truncal/
retroperitoneal primary sites

77. Research
• Cancer stem cells of rhabdomyosarcoma have been
identified and fibroblast growth factor receptor 3 has
been suggested as their marker. Preclinical animal
studies that try to use conditionally replicating
adenoviruses against such cells are in progress.
• Survivin-responsive conditionally replicating
adenovirus kills rhabdomyosarcoma stem cells more
efficiently than their progeny-
Tanoue et al. Journal of Translational Medicine 2014,
12:27.

79. Thank you.