| Low risk: Surgery 1st, then chemo. If group I → chemo only, no RT. All pts with initial +node must get RT regardless of response to induction chemo or SLS (at least 41.4 Gy, 50.4 Gy to gross Dz). Vincristine is given with RT and dactinomycin is given at wk 13 prior to RT, but they are not given concurrently. |
| Target volume: GTV—pre-Tx volume + involved LN; CTV = GTV + 1 cm; PTV = CTV + 0.5 cm. For CG-III to 50.4 Gy, CD at 36 Gy to pre-Tx GTV + 0.5 cm (CTV), with PTV = CTV + 0.5 cm. The planning OAR volume is based on organs at risk; GTV can be defined by exam, CT, MRI, or PET. |
| Timing: RT begins wk 13 after postop chemo. The exceptions are those who get SLS and those with vaginal primaries. For those who get SLS, RT starts after surgery at wk 13 (to allow time for healing). |
| All pts with initial CG-III in a favorable site (stage I, except orbit and paratesticular sites) should be considered for SLS at wk 13. |
| Intermediate risk: RT given at wk 4 (compare with data from wk 10 on IRS-IV). IMRT/proton/brachytherapy/electron and PET imaging are all allowed. CRT = VC or VI concurrently. Simulation occurs before wk 4 to begin on time. |
| Margins: CD after 36 Gy for tumors with “pushing” rather than invasive (lung, intestine, bladder). Boost to 50.4 Gy with new GTV representing response + 1 cm (CTV) and 0.5 cm (PTV). If 36 or 41.4 Gy, there is no volume reduction. GTV is pre-Tx volume + margin, except intrathoracic or intra-abdominal tumors (GTV as pre-Tx volume excluding intrathoracic or intra-abdominal/pelvic tumor from which it was debulked, since these are “pushing” borders). |
| Timing: All at wk 4. Emergency RT for symptomatic cord compression and high-risk PM (intracranial extension) can be given on wk 1 (day 1). Management of BOS erosion and CN palsy was not specified in the protocol, so it can be managed according to the discretion of the radiation oncologist. |
| High risk: RT given on wk 20 to primary and metastatic sites (except high-risk PM sites with IC extension and emergency RT). |
| High-risk PM sites with only BOS and/or CN palsy will get RT at wk 20. PM sites with intracranial extension will rcv RT at wk 1 (day 0) (but within 2 wks of the 1st cycle of chemo to start RT) and Tx to the metastatic site at wk 20 (unless the metastatic site is within the same Tx port as the primary). Emergency RT for cord compression is on day 0. |
| CRT: VI is given concurrently with RT, starting on wk 19 (day 0 if an emergency or PM with IC). Alternative: VC, if VI is not tolerable. |
| Margins: CD after 36 Gy for tumors with “pushing” rather than invasive (lung, intestine, bladder). Boost to 50.4 Gy with new GTV representing response + 1 cm (CTV) and 0.5 cm (PTV). If 36 or 41.4 Gy, GTV is pre-Tx volume + margin. |
| Bilat whole lung 15 Gy (10 fx) for pulmonary mets or pleural effusion (can boost to gross Dz) to 50.4 Gy. |
IRS, International Rhabdomyosarcoma Study; chemo, chemotherapy; RT, radiation therapy; pt, patient; +node, positive node; SLS, second-look surgery; Gy, gray; Dz, disease; wk, week; GTV, gross target volume; Tx, treatment; LN, lymph node; CTV, clinical target volume; cm, centimeter; PTV, planning target volume; CG, clinical group; CD, cone down; exam, examination; CT, computed tomography; MRI, magnetic resonance imaging; PET, positron emission tomography; postop, postoperative; IMRT, intensity modulated radiation therapy; CRT, chemoradiation; VC, vincristine/Cytoxan; VI, vincristine/irinotecan; PM, parameningeal; BOS, base of skull; CN, cranial nerve; IC, internal carotid; rcv, receive; bilat, bilateral; fx, fraction; met, metastasis.