A J A Y M A N I C K A MF E L L O W , H E A D N E C K S U R G E R Y

T A T A M E D I C A L C E N T R E

INTER GROUP RHABDOMYOSARCOMA STUDY GROUP (IRSG)

RHABDOMYOSARCOMA• Most common type of childhood soft tissue

sarcoma. Head neck is MC site.• Histologic classification

Embryonal

Botryoid

Spindle-cell

Alveolar

PRESENTATION• Swelling • Location of tumour Nasal discharge, airway obstruction, otorrhea, fetor, proptosis

DIAGNOSTIC WORKUP1. Nature and extent of primary disease – Bx +

CT/MRI2. Locoregional/ metastatic disease +/- - Bone

marrow biopsy, chest CT, Bone scan, if para meningeal – lumbar puncture for CSF cytology.

IRSG STUDY• IRSG – formed under National Cancer Institute in

1972AIMS1. Investigate therapy of RMS and Undifferentiated

sarcoma (UDS)2. Investigate Biology of RMS and UDS

Patients were mainly <21 yrs of age.

IRS (I-1V)• 5 Successive protocols in 4292 patients are

completed. 1. IRS – I 1972 – 1978 2. IRS – II 1978 – 19843. IRS – III 1984 – 1991 4. IRS – IV (PILOT) 1987 – 19915. IRS – IV 1991 - 1997

AIMS & OBJECTIVES 1. To summarize lessons from IRSG protocols. 2. Outline current therapeutic approaches for

newly diagnosed patients.

IRSG SURGICAL – PATHOLOGICAL GROUPING SYSTEM

1. I - Localized tumour, completely removed with pathologically clear margins and no regional lymph node involvement

2. II - Localized tumour, grossly removed with (a) microscopically involved margins, (b) involved, grossly resected regional lymph nodes, or (c) both

3. III - Localized tumour, with gross residual disease after grossly incomplete removal, or biopsy only

4. IV - Distant metastases present at diagnosis

IRSG STAGING SYSTEM

RESULTS IRS I-IV

1.Surgery 2.Radiotherapy3.Chemotherapy4.Patho-Biologic

SURGERY • Group I – best prognosis for 5 year failure free

survival and overall survival. • Group – IV – Worst outlook• Group II, III – Intermediate prognosis. • Lesion excised without knowledge - needs wide re

excision. • Preservation of eye is desirable. Primary

chemotherapy followed by RT. • Node positive tumour – RT + Chemo

(Cyclophosphamide, vincristine, actinomycin D)

RADIATION THERAPY• Group I + Embryonal subtype – no additional

advantage on giving RT• Other groups – primary tumour and regional lymph

nodal area to be irradiated. • Group II – intensified therapy – improved outcome

(41Gy)• Group III – local failure rates in H&N – 12% (50Gy)• Intra cranial extension – managed by CT and RT• 2cm margin is sufficient.

CHEMOTHERAPY • V – Vincristine• A – Actinomycin D• C – Cyclophosphamide (2.2g/metre sq)• To be combined with GCSF – failure free and

overall survival is better. (19-44%)• VAI – Ifosfamide• VIE – Etoposide

PATHOLOGY AND BIOLOGY• Alveolar RMS – intensified therapy• In alveolar type, Translocations of tumour (t2;13)

older patient bad prognosis where as (t1;13) younger patient good prognosis.• Group with RT and CT – risk of second primary is

common. Hence needs follow up.

IRS V STUDY• Risk of recurrence1. Low risk – 3 year FFS (failure free survival) -

88% 2. Intermediate - 3 year FFS – 55-76%3. High risk – 3 year FFS <30%

IRS V RECOMMENDATIONS•Multidisciplinary treatment as defined by Histology. •Goal is to achieve local control with preservation of form and function.

CONCLUSION• IRSG V – protocol incorporate recommendations

for risk based management.

REFERENCES1 Maurer HM, Beltangady M, Gehan EA, et al. The Intergroup Rhabdomyosarcoma Study-I. A final report. Cancer 1988; 61:209± 20.2 Maurer HM, Gehan EA, Beltangady M, et al. The Intergroup Rhabdomyosarcoma Study-II. Cancer 1993;71:1904± 22.3 Crist W, Gehan EA, Ragab AH, et al. The Third Intergroup Rhabdomyosarcoma Study. J Clin Oncol 1995;13:610± 30.4 Ortega JA, Ragab AH, Gehan EA, et al. A feasibility, toxicity, and efficacy study of ifosfamide, actinomycin D, and vincristine for the treatment of childhood rhabdomyosarcoma: a report of the Intergroup Rhabdomyosarcoma Study IV Pilot Study. Am J Pediatr Hematol Oncol 1993; 15(suppl A):S15± 20.5 Ruymann FB, Vietti T, Gehan E, et al. Cyclophosphamide dose escalation in combination with vincristine and actinomycin D (VAC) in gross residual sarcoma:

REFRENCES6 Arndt C, Tefft M, Gehan E, et al. A feasibility, toxicity,and early response study of etoposide, ifosfamide, and vincristine for the treatment of children with rhabdomyosarcoma:a report from the Intergroup Rhabdomyosarcoma Study (IRS) IV Pilot Study. J Pediatr Oncol 1997; 19:124±9.7 Crist W, Anderson J, Maurer H, et al. Preliminary results for patients with local/regional tumors treated on the Intergroup Rhabdomyosarcoma Study-IV(1991± 97) [abstract 2141]. Proc Am Soc Clin Oncol1999; 18:555a.8 Lawrence W Jr, Anderson JR, Gehan EA, et al. Pretreatment TNM staging of childhood rhabdomyosarcoma: a report of the Intergroup Rhabdomyosarcoma Study Group. Cancer 1997; 80:1165± 70.9 Hays DM, Lawrence W Jr, Wharam M, et al. Primary reexcision for patients with `microscopic residual’ tumor following initial excision of sarcomas of trunk and extremity sites. J Pediatr Surg 1989; 24:5± 10. 10 Lawrence W Jr, Hays DM, Heyn R, et al. Surgical lessons from the Integroup Rhabdomyosarcoma Study (IRS) pertaining to extremity tumors. World J Surg 1988; 12:676± 84.