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Esthesioneuroblastoma: an update on the massachusetts eye and ear infirmary and massachusetts general hospital experience with craniofacial resection, proton beam radiation, and chemotherapy.

ABSTRACT: Objectives To update the Massachusetts General Hospital (MGH) and Massachusetts Eye and Ear Infirmary (MEEI) experience in the management of esthesioneuroblastoma (ENB) with multimodality therapy and to reassess treatment outcomes and complications in a larger cohort with longer follow-up times. Design A retrospective chart review. Setting A tertiary referral center. Participants All patients presenting with ENB and managed at the MGH and MEEI from 1997 to 2013. Main Outcome Measures Disease-free and overall survival. Results Twenty-two patients were identified with an average follow-up of 73 months. Ten patients presented with Kadish stage B disease and 12 with stage C disease. A total of six patients (27%) developed regional metastases. Treatment for all patients included craniofacial resection (CFR) followed by proton beam irradiation with or without chemotherapy. The 5-year disease-free and overall survival rates were 86.4% and 95.2%, respectively, by Kaplan-Meier analysis. Negative margins were a significant factor in disease-free survival. One patient experienced severe late-radiation toxicity. Conclusions ENB is safely and effectively treated with CFR followed by proton beam irradiation. The high incidence of regional metastases warrants strong consideration for elective neck irradiation. Proton beam radiation is associated with lower rates of severe late-radiation toxicity than conventional radiotherapy.

SUBMITTER: Herr MW

PROVIDER: S-EPMC3912136 | biostudies-other | 2014 Feb

REPOSITORIES: biostudies-other

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Project description:Proton radiotherapy using minibeams of sub-millimeter dimensions reduces side effects in comparison to conventional proton therapy due to spatial fractionation. Since the proton minibeams widen with depth, the homogeneous irradiation of a tumor can be ensured by adjusting the beam distances to tumor size and depth to maintain tumor control as in conventional proton therapy. The inherent advantages of protons in comparison to photons like a limited range that prevents a dosage of distal tissues are maintained by proton minibeams and can even be exploited for interlacing from different beam directions. A first animal study was conducted to systematically investigate and quantify the tissue-sparing effects of proton pencil minibeams as a function of beam size and dose distributions, using beam widths between ? = 95, 199, 306, 411, 561 and 883 ?m (standard deviation) at a defined center-to-center beam distance (ctc) of 1.8 mm. The average dose of 60 Gy was distributed in 4x4 minibeams using 20 MeV protons (LET ~ 2.7 keV/?m). The induced radiation toxicities were measured by visible skin reactions and ear swelling for 90 days after irradiation. The largest applied beam size to ctc ratio (?/ctc = 0.49) is similar to a homogeneous irradiation and leads to a significant 3-fold ear thickness increase compared to the control group. Erythema and desquamation was also increased significantly 3-4 weeks after irradiation. With decreasing beam sizes and thus decreasing ?/ctc, the maximum skin reactions are strongly reduced until no ear swelling or other visible skin reactions should occur for ?/ctc < 0.032 (extrapolated from data). These results demonstrate that proton pencil minibeam radiotherapy has better tissue-sparing for smaller ?/ctc, corresponding to larger peak-to-valley dose ratios PVDR, with the best effect for ?/ctc < 0.032. However, even quite large ?/ctc (e.g. ?/ctc = 0.23 or 0.31, i.e. PVDR = 10 or 2.7) show less acute side effects than a homogeneous dose distribution. This suggests that proton minibeam therapy spares healthy tissue not only in the skin but even for dose distributions appearing in deeper layers close to the tumor enhancing its benefits for clinical proton therapy.

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Esthesioneuroblastoma: an update on the massachusetts eye and ear infirmary and massachusetts general hospital experience with craniofacial resection, proton beam radiation, and chemotherapy.

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