TY - JOUR
T1 - Patterns of failure following proton beam therapy for head and neck rhabdomyosarcoma
AU - Ludmir, Ethan B.
AU - Grosshans, David R.
AU - McAleer, Mary Frances
AU - McGovern, Susan L.
AU - Harrison, Douglas J.
AU - Okcu, M. Fatih
AU - Chintagumpala, Murali M.
AU - Mahajan, Anita
AU - Paulino, Arnold C.
N1 - Publisher Copyright:
© 2019 Elsevier B.V.
PY - 2019/5
Y1 - 2019/5
N2 - Purpose: Pediatric patients with rhabdomyosarcoma (RMS) of the head and neck (H&N) are treated with multimodal therapy, often with radiotherapy (RT) as definitive local therapy. We report on the patterns of failure following proton beam therapy (PBT) for H&N RMS. Methods: Forty-six H&N RMS patients were enrolled on a prospective registry protocol between 2006 and 2015. All were treated with a combination of chemotherapy (ChT) and PBT. Most patients (25 patients, 54%) had parameningeal tumors, of which 11 (24%) had intracranial extension (ICE). Thirteen patients (28%) had primary tumors greater than 5 cm. Median total cyclophosphamide (CPM) equivalent dose was 13.2 g/m 2 (range 0–16.8 g/m 2 ). Median RT dose was 50.4 Gy(RBE) (range 36 Gy[RBE]–50.8 Gy[RBE]). Results: With median follow-up of 3.9 years, five-year overall survival was 76%, and five-year progression-free survival was 57%. Seventeen patients (37%) experienced relapse, including 7 with local failure (LF). Five-year local control (LC) was 84%. Tumor size greater than 5 cm predicted increased risk of LF (hazard ratio [HR] 6.49, p = 0.03), as did the presence of ICE at diagnosis (HR 5.21, p = 0.03). Six relapses occurred in patients with ICE; all included a component of central nervous system relapse, with leptomeningeal disease and/or LF with an intracranial component. Delayed RT delivery after week 4 of ChT predicted increased risk of relapse for ICE patients (HR 10.49, p = 0.006). Conclusions: PBT confers excellent LC, and a favorable late toxicity profile as compared with prior photon RT data. Our observations support ongoing trial efforts to dose-escalate RT for patients with larger tumors. However, these data raise concerns regarding excess failures among patients with ICE.
AB - Purpose: Pediatric patients with rhabdomyosarcoma (RMS) of the head and neck (H&N) are treated with multimodal therapy, often with radiotherapy (RT) as definitive local therapy. We report on the patterns of failure following proton beam therapy (PBT) for H&N RMS. Methods: Forty-six H&N RMS patients were enrolled on a prospective registry protocol between 2006 and 2015. All were treated with a combination of chemotherapy (ChT) and PBT. Most patients (25 patients, 54%) had parameningeal tumors, of which 11 (24%) had intracranial extension (ICE). Thirteen patients (28%) had primary tumors greater than 5 cm. Median total cyclophosphamide (CPM) equivalent dose was 13.2 g/m 2 (range 0–16.8 g/m 2 ). Median RT dose was 50.4 Gy(RBE) (range 36 Gy[RBE]–50.8 Gy[RBE]). Results: With median follow-up of 3.9 years, five-year overall survival was 76%, and five-year progression-free survival was 57%. Seventeen patients (37%) experienced relapse, including 7 with local failure (LF). Five-year local control (LC) was 84%. Tumor size greater than 5 cm predicted increased risk of LF (hazard ratio [HR] 6.49, p = 0.03), as did the presence of ICE at diagnosis (HR 5.21, p = 0.03). Six relapses occurred in patients with ICE; all included a component of central nervous system relapse, with leptomeningeal disease and/or LF with an intracranial component. Delayed RT delivery after week 4 of ChT predicted increased risk of relapse for ICE patients (HR 10.49, p = 0.006). Conclusions: PBT confers excellent LC, and a favorable late toxicity profile as compared with prior photon RT data. Our observations support ongoing trial efforts to dose-escalate RT for patients with larger tumors. However, these data raise concerns regarding excess failures among patients with ICE.
KW - Cyclophosphamide
KW - Intracranial extension
KW - Parameningeal
KW - Proton beam therapy
KW - Radiotherapy
KW - Rhabdomyosarcoma
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U2 - 10.1016/j.radonc.2019.02.002
DO - 10.1016/j.radonc.2019.02.002
M3 - Article
C2 - 31005208
AN - SCOPUS:85061441375
SN - 0167-8140
VL - 134
SP - 143
EP - 150
JO - Radiotherapy and Oncology
JF - Radiotherapy and Oncology
ER -