Intensity Modulated Radiation Therapy With Dose Painting to Treat Rhabdomyosarcoma
To examine local control and patterns of failure in rhabdomyosarcoma patients treated with intensity modulated radiation therapy (RT) with dose painting (DP-IMRT).
A total of 41 patients underwent DP-IMRT with chemotherapy for definitive treatment. Nineteen also underwent surgery with or without intraoperative RT. Fifty-six percent had alveolar histologic features. The median interval from beginning chemotherapy to RT was 17 weeks (range, 4-25). Very young children who underwent second-look procedures with or without intraoperative RT received reduced doses of 24-36 Gy in 1.4-1.8-Gy fractions. Young adults received 50.4 Gy to the primary tumor and lower doses of 36 Gy in 1.8-Gy fractions to at-risk lymph node chains.
With 22 months of median follow-up, the actuarial local control rate was 90%. Patients aged ≤7 years who received reduced overall and fractional doses had 100% local control, and young adults had 79% (P=.07) local control. Three local failures were identified in young adults whose primary target volumes had received 50.4 Gy in 1.8-Gy fractions.
DP-IMRT with lower fractional and cumulative doses is feasible for very young children after second-look procedures with or without intraoperative RT. DP-IMRT is also feasible in adolescents and young adults with aggressive disease who would benefit from prophylactic RT to high-risk lymph node chains, although dose escalation might be warranted for improved local control. With limited follow-up, it appears that DP-IMRT produces local control rates comparable to those of sequential IMRT in patients with rhabdomyosarcoma.
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ABSTRACT: Late effects of treatment are an important cause of morbidity and mortality in childhood cancer survivors. The use of radiotherapy has been implicated as a risk factor for the development of many late complications. Several strategies have been employed in pediatric oncology to minimize the late effects of radiotherapy. These have included (1) omitting or delaying radiotherapy until the child is older, (2) decreasing radiotherapy doses and volumes by incorporating chemotherapy in the treatment regimen, (3) alteration of radiotherapy fractionation, (4) use of novel techniques to spare or minimize radiation dose to surrounding normal tissues, and (5) elimination of radiotherapy in favorable subsets of patients. In infants with brain tumors, delaying radiotherapy and giving chemotherapy until the child is 3 years old was a popular approach three to four decades ago with limited success with respect to tumor control. With the advent of modern radiotherapy technology, younger patients are now able to be treated with conformal techniques and reasonable neurotoxicity. Using chemotherapy to reduce doses of radiation therapy has been employed in standard-risk medulloblastoma, intracranial germinoma, Hodgkin lymphoma, and Wilms’ tumor. Likewise, the use of chemotherapy to reduce radiotherapy volumes has been employed in intracranial germinoma, Hodgkin lymphoma, and neuroblastoma and for the boost portion of treatments for rhabdomyosarcoma and Ewing sarcoma. There are a few phase III trials comparing conventional and hyperfractionated radiotherapy, but none of them have shown superiority of one over the other in terms of tumor control and late effects. Current protocols are testing the omission of radiotherapy in the most favorable subset of patients with Hodgkin lymphoma and Wilms’ tumor. Intensity-modulated radiation therapy is currently used in many children in developed nations. Proton therapy is available in a few centers; clinical results of treatment are accumulating regarding the effectiveness and long-term toxicity of this radiation modality.
Available from: Natia Esiashvili
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ABSTRACT: Rhabdomyosarcoma (RMS) is the most common soft tissue sarcoma in children, affecting very young patients. These tumors often cause significant functional damage because of their aggressive growth pattern. In addition, their metastatic potential can present as a complex and challenging situation. RMS can present in various anatomical sites and often pose significant obstacle in choosing local control modalities. When feasible, surgery plays an important role for initial diagnosis and complete tumor removal; delayed primary re-excision and second-look surgery after initial chemotherapy are gaining more acceptance. Because of high-metastatic risk, systemic chemotherapy is also necessary. Novel agents are emerging which may alter the disease course in high-risk disease where the cure rate is still low. Radiation therapy is an important tool in the management of RMS and has gone through significant evolution during past four decades. This review will outline treatment strategies adopted in children RMS. The primary focus will be the North American approach with attention to advancements in radiation therapy, surgical techniques, and systemic therapies.
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To examine patterns of failure in patients with parameningeal rhabdomyosarcoma (PM-RMS) treated with intensity modulated radiation therapy (IMRT).
Methods and materials:
Forty-seven patients with PM-RMS received chemotherapy and IMRT for definitive treatment. The median age was 9 years (range, 0.5-35 years). The high-risk features were as follows: 40% alveolar histology, 72% group III and 26% group IV disease, 57% either intracranial extension (ICE) (n=25) or cranial neuropathy (n=21). The median time to RT from the start of chemotherapy was 15 weeks (range, 2-54 weeks). Patients received 50.4 Gy in 1.8-Gy fractions to the primary tumor by use of IMRT. Thirteen patients aged≥14 years with alveolar histology received 36 Gy prophylactic nodal irradiation (PNI) to bilateral cervical nodes. Events were defined as local, regional (nodal), central nervous system (CNS), or distant failures.
With a median follow-up time of 3.3 years (range, 0.5-12.8 years), 18 patients experienced failure: 5 local, 2 regional, 6 distant, and 7 CNS. The 5-year local failure-free survival was 86%. Age, histology, and time to RT did not influence the risk of local failure. The 5-year regional failure-free survival was 92%: 100% for embryonal and 74% for alveolar (P=.03). However, there were no lymph node failures in patients with alveolar histology who were given PNI. The 5-year CNS failure-free survival was 83%: 100% without and 70% with ICE (P=.01); 95% without and 69% with cranial neuropathy (P=.02). The estimated 5-year event-free survival and overall survival were 61% for group III and 58% for group IV patients.
Distant failure was the most common type of failure among group IV patients. Patients with alveolar histology seem to benefit from PNI. The presence of ICE or cranial neuropathy portends a high risk of CNS failure, the most common pattern of failure among non-group IV patients. These patients may benefit from the addition of novel CNS-directed therapy.
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