RESUMO
PURPOSE: Craniospinal irradiation (CSI) improves clinical outcomes at the cost of long-term neuroendocrine and cognitive sequelae. The purpose of this pilot study was to determine whether hypothalamic-pituitary axis (HPA) and hippocampus avoidance (HPA-HA) with intensity-modulated proton therapy (IMPT) can potentially reduce this morbidity compared with standard x-ray CSI. MATERIALS AND METHODS: We retrospectively evaluated 10 patients with medulloblastoma (mean, 7 years; range, 4-14 years). Target volumes and organs at risk were delineated as per our local protocol and the ACNS0331 atlas. An experienced neuroradiologist verified the HPA and hippocampus contours. The primary objective was CSI and boost clinical target volume (CTV) covering 95% of the volume (D95) > 99% coverage with robustness. Described proton therapy doses in grays are prescribed using a biological effectiveness relative to photon therapy of 1.1. The combined prescribed dose in the boost target was 54 Gy. Secondary objectives included the HPA and hippocampus composite average dose (Dmean ≤ 18 Gy). For each patient, volumetric modulated arc radiotherapy (VMAT) and tomotherapy (TOMO) plans existed previously, and a new plan was generated with 3 cranial and 1 or 2 spinal beams for pencil-beam scanning delivery. Statistical comparison was performed with 1-way analysis of variance. RESULTS: Compared with standard CSI, HPA-HA CSI had statistically significant decreases in the composite doses received by the HPA (32.2 versus 17.9 Gy; P < .001) and hippocampi (39.8 versus 22.8 Gy; P < .001). The composite HPA Dmean was lower in IMPT plans (17.9 Gy) compared with that of VMAT (21.8 Gy) and TOMO (21.2 Gy) plans (P = .05). Hippocampi composite Dmean was also lower in IMPT plans (21 Gy) compared with that of VMAT (27.5 Gy) and TOMO (27.2 Gy) plans (P = .02). The IMPT CTV D95 coverage was lower in IMPT plans (52.8 Gy) compared with that of VMAT (54.6 Gy) and TOMO (54.6 Gy) plans (P < .001) The spared mean volume was only 1.35% (19.8 cm3) of the whole-brain CTV volume (1476 cm3). CONCLUSION: We found that IMPT has the strong potential to reduce the dose to the HPA and hippocampus, compared with standard x-ray CSI while maintaining target coverage. A prospective clinical trial is required to establish the safety, efficacy, and toxicity of this novel CSI approach.
RESUMO
The use of radiation therapy has been increasing over recent years for the treatment of hepatocellular carcinoma (HCC). Proton beam therapy (PBT) has emerged as a promising treatment option for HCC patients due to its dosimetric advantages of sparing more normal liver tissue from radiation at low to moderate doses compared to photon-based treatments while still delivering high doses of radiation to tumors. The PBT therapy may be particularly beneficial in high-risk HCC cirrhotic patients with large, bulky tumors and/or vascular invasion complicated by surrounding perfusion abnormalities. We present a case of a 62-year-old male with an unresectable 13 cm diffusely infiltrative HCC tumor with main portal vein invasion and elevated alpha-feta protein (AFP) of 37,200 that was intolerant of standard sorafenib treatment. He was treated with hypofractionated PBT to 67.5 GyE in 15 fractions using a novel combination of simultaneously integrated boost intensity modulated proton therapy (SIB-IMPT), breath hold technique, and functional liver imaging with technetium-99m [99mTc] sulfur colloid single-photon emission computed tomography (SPECT/CT) to assist in the differentiation of tumor and normal liver. He had a complete radiographic and biochemical response by AFP normalization by seven months post-treatment without evidence of radiation hepatotoxicity.