Intergroup Rhabdomyosarcoma Study Staging Research Articles

Patterns of Failure in Pediatric Rhabdomyosarcoma After Proton Therapy

To report on the patterns of failure in children with rhabdomyosarcoma treated with proton therapy. Between February 2007 and November 2013, 66 children with a median age of 4.1years (range, 0.6-15.3years) diagnosed with nonmetastatic rhabdomyosarcoma were treated with proton therapy. Clinical target volume 1 was defined as the prechemotherapy tumor plus a 1-cm anatomically constrained margin. Clinical target volume 2 was defined as the postchemotherapy tumor (or tumor bed) plus a 0.5-cm anatomically constrained margin, further expanded to encompass potential pathways of spread, including soft tissue infiltrated with tumor at diagnosis. Of the 66 children, 11 developed locally progressive disease at a median of 16months (range, 14-32months), for an actuarial 2-year local control rate of 88%. Among the children who progressed, median age and tumor size at diagnosis were 6.7years (range, 0.6-16years) and 6cm (range, 2-8cm), respectively. Of the recurrences, 64% and 36% were embryonal and alveolar, respectively. Disease progression was observed in 7 (64%) parameningeal, 2 (18%) head and neck (other), and 2 (18%) bladder/prostate subsites. At diagnosis, 8 of 11 patients who developed a recurrence were Intergroup Rhabdomyosarcoma Study stage 3, and all 11 were group III. Of the relapses, 100% (11 of 11) were confirmed as in-field within the composite 95% isodose line. One of the 11 patients (9%) developed a new simultaneous regional nodal recurrence outside of the previously treated radiation field. Early data suggest that the sharp dosimetric gradient associated with proton therapy is not associated with an increased risk of marginal failure. Routine use of a 0.5- to 1-cm clinical target volume 1/2 margin with highly conformal proton therapy does not compromise local control in children diagnosed with rhabdomyosarcoma with unfavorable risk features.

Reconstructive option after radical mutilating surgery in children with genitourinary rhabdomyosarcoma: When sparing the bladder is not an option.

To present versatile surgical reconstructive techniques and their outcomes in pediatric patients with genitourinary rhabdomyosarcoma. We retrospectively analyzed the oncological and urological outcomes of seven patients treated between 1992 and 2014 according to the Cooperative Weichteilsarkom Studiengruppe protocols. Intergroup Rhabdomyosarcoma Study staging: local, six patients; and IV, one patient. embryonal, five patients; unclassified, one patient; triton tumor one patient. Surgical treatment included: cystectomy, uterectomy and partial vaginectomy, one patient; radical cystectomy, two patients; cystectomy, one patient; cystectomy with partial prostatectomy, one patient; partial cystectomy, one patient; and partial prostatectomy, one patient. All patients were alive in complete remission at last follow up. In four cases, ileal conduit with ureteral reimplantation with serous-lined extramural tunnel (Abol-Enein technique) was carried out, which was followed by conversion into ileal continent bladder with continent appendiceal stoma for clean intermittent catheterization in three patients. In one boy, partial cystectomy and continent reconstruction was carried out during a single surgical procedure. One child with incontinent urinary diversion is still awaiting a continence solution. One child after partial prostatectomy is continent without any voiding disturbances. The timing and extent of radical surgery for treatment of genitourinary rhabdomyosarcoma depend on the local anatomical conditions, and the response to previous chemo- and radiotherapy. Cystectomy followed by various reconstructive techniques still remains an important option in the local treatment.

Rhabdomyosarcoma: New Windows of Opportunity

Rhabdomyosarcoma is a highly malignant, small blue cell tumor characterized by muscle differentiation. With modern treatment, more than 70% of children and adolescents with this disease are cured. Adequate biopsy to obtain sufficient tissue for accurate diagnosis and molecular characterization is critical. Patients must be assessed for tumor extent; the Intergroup Rhabdomyosarcoma Study (IRS) clinical group and Staging system is universally applied in North America. Multidisciplinary therapy is necessary to maximize cure rates. Local control relies on complete surgical excision when possible; those whose tumors are not completely excised and those with alveolar histology tumors require local irradiation to maximize local control. In North America, vincristine (Oncovin); Eli Lilly and Company, Indianapolis, http://www.lilly.com), dactinomycin (Cosmegen); Merck & Co., Inc., Whitehouse Station, NJ, http://www.merck.com), and cyclophosphamide are the standard chemotherapy agents. The IRS has used therapeutic window studies to confirm the predictive nature of preclinical xenograft models and to identify several new single agents and combinations of agents with activity in high-risk patient groups. Despite these efforts, the outcome for these high-risk patients remains poor. The next generation of Children's Oncology Group studies will evaluate the efficacy of topoisomerase-I inhibitors and dose-compression therapy approaches. New advances in molecular characterization of tumors, including gene-expression analysis, may identify new therapeutic targets that can be exploited by expanded preclinical drug discovery efforts, and hold the promise of revolutionizing risk-based therapies.