IRSG - JOURNAL PAPER

1. A J A Y M A N I C K A M
F 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)

2. RHABDOMYOSARCOMA
• Most common type of childhood soft tissue sarcoma.
Head neck is MC site.
• Histologic classification
Embryonal
Botryoid
Spindle-
cell
Alveolar

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

4. DIAGNOSTIC WORKUP
1. Nature and extent of primary disease – Bx + CT/MRI
2. Locoregional/ metastatic disease +/- - Bone marrow
biopsy, chest CT, Bone scan, if para meningeal –
lumbar puncture for CSF cytology.

5. IRSG STUDY
• IRSG – formed under National Cancer Institute in 1972
AIMS
1. Investigate therapy of RMS and Undifferentiated
sarcoma (UDS)
2. Investigate Biology of RMS and UDS
Patients were mainly <21 yrs of age.

6. IRS (I-1V)
• 5 Successive protocols in 4292 patients are completed.
1. IRS – I 1972 – 1978
2. IRS – II 1978 – 1984
3. IRS – III 1984 – 1991
4. IRS – IV (PILOT) 1987 – 1991
5. IRS – IV 1991 - 1997

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

8. 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

9. IRSG STAGING SYSTEM

10. RESULTS IRS I-IV
1. Surgery
2. Radiotherapy
3. Chemotherapy
4. Patho-Biologic

11. 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)

12. 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.

13. 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

14. 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.

15. IRS V STUDY
• Risk of recurrence
1. Low risk – 3 year FFS (failure free survival) - 88%
2. Intermediate - 3 year FFS – 55-76%
3. High risk – 3 year FFS <30%

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

18. CONCLUSION
• IRSG V – protocol incorporate recommendations for risk
based management.

19. REFERENCES
1 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:

20. REFRENCES
6 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.