The feasibility of dose escalation using intensity-modulated radiotherapy (IMRT) and intensity-modulated proton therapy (IMPT) with FDG PET/CT guided in esophageal cancer.

Zhang Y ，Fan B ，Sun T ，Xu J ，Yin Y ，Chen Z ，Zhu J ，Yu J ，Hu M ... -  《-》

Intensity-modulated proton therapy further reduces normal tissue exposure during definitive therapy for locally advanced distal esophageal tumors: a dosimetric study.

We have previously found that ≤ 75% of treatment failures after chemoradiotherapy for unresectable esophageal cancer appear within the gross tumor volume and that intensity-modulated (photon) radiotherapy (IMRT) might allow dose escalation to the tumor without increasing normal tissue toxicity. Proton therapy might allow additional dose escalation, with even lower normal tissue toxicity. In the present study, we compared the dosimetric parameters for photon IMRT with that for intensity-modulated proton therapy (IMPT) for unresectable, locally advanced, distal esophageal cancer. Four plans were created for each of 10 patients. IMPT was delivered using anteroposterior (AP)/posteroanterior beams, left posterior oblique/right posterior oblique (LPO/RPO) beams, or AP/LPO/RPO beams. IMRT was delivered with a concomitant boost to the gross tumor volume. The dose was 65.8 Gy to the gross tumor volume and 50.4 Gy to the planning target volume in 28 fractions. Relative to IMRT, the IMPT (AP/posteroanterior) plan led to considerable reductions in the mean lung dose (3.18 vs. 8.27 Gy, p<.0001) and the percentage of lung volume receiving 5, 10, and 20 Gy (p≤.0006) but did not reduce the cardiac dose. The IMPT LPO/RPO plan also reduced the mean lung dose (4.9 Gy vs. 8.2 Gy, p<.001), the heart dose (mean cardiac dose and percentage of the cardiac volume receiving 10, 20, and 30 Gy, p≤.02), and the liver dose (mean hepatic dose 5 Gy vs. 14.9 Gy, p<.0001). The IMPT AP/LPO/RPO plan led to considerable reductions in the dose to the lung (p≤.005), heart (p≤.003), and liver (p≤.04). Compared with IMRT, IMPT for distal esophageal cancer lowered the dose to the heart, lung, and liver. The AP/LPO/RPO beam arrangement was optimal for sparing all three organs. The dosimetric benefits of protons will need to be tailored to each patient according to their specific cardiac and pulmonary risks. IMPT for esophageal cancer will soon be investigated further in a prospective trial at our institution.

Welsh J ，Gomez D ，Palmer MB ，Riley BA ，Mayankkumar AV ，Komaki R ，Dong L ，Zhu XR ，Likhacheva A ，Liao Z ，Hofstetter WL ，Ajani JA ，Cox JD ... -  《-》

Dosimetric comparison of intensity modulated radiotherapy and intensity modulated proton therapy in the treatment of recurrent nasopharyngeal carcinoma.

To compare the dosimetric performance of Intensity Modulated Proton Therapy (IMPT) and Intensity Modulated Radiotherapy (IMRT) in terms of target volume coverage and sparing of neurological organs-at-risk (OARs) in salvaging recurrent nasopharyngeal carcinoma (rNPC). The maximum dose to the internal carotid artery (ICA) and nasopharyngeal (NP) mucosa, which are associated with potential carotid blowout and massive epistaxis, were also evaluated. IMRT and IMPT treatment plans were created for twenty patients with locally advanced rNPC. Planning Target Volume (PTV) was used to account for the setup and spatial error/uncertainty in the IMRT planning. Robust optimization on Clinical Target Volume (CTV) coverage with consideration of range and setup uncertainty was employed to produce two IMPT plans with 3-field and 4-field arrangements. The planning objective was to deliver 60 Gy to the PTV (IMRT) and CTV (IMPT) without exceeding the maximum lifetime cumulative Biologically Effective Dose (BED) of the neurological OARs (applied to the Planning organs-at-risk volume). The target dose coverage as well as the maximum dose to the neurological OARs, ICA, and NP mucosa were compared. Compared with IMRT, 3-field IMPT achieved better coverage to GTV V100% (83.3% vs. 73.2%, P <0.01) and CTV V100% (80.5% vs. 72.4%, P <0.01), and lower maximum dose to the critical OARs including the spinal cord (19.2 Gy vs. 22.3 Gy, P <0.01), brainstem (30.0 Gy vs. 32.3 Gy, P <0.01) and optic chiasm (6.6 Gy vs. 9.8 Gy, P <0.01). The additional beam with the 4-fields IMPT plans further improved the target coverage from the 3-field IMPT (CTV V98%: 85.3% vs. 82.4%, P <0.01) with similar OAR sparing. However, the target dose was highly non-uniform with both IMPT plans, leading to a significantly higher maximum dose to the ICA (∼68 Gy vs. 62.6 Gy, P <0.01) and NP mucosa (∼72 Gy vs. 62.8 Gy, P <0.01) than IMRT. IMPT demonstrated some dosimetric advantage over IMRT in treating rNPC. However, IMPT could also result in very high dose hot spots in the target volume. Careful consideration of the ICA and NP mucosal complications is recommended when applying IMPT on rNPC patients.

Hung HM ，Chan OCM ，Mak CH ，Hung WM ，Ng WT ，Lee MCH ... -  《-》

(18) F-Fluoromisonidazole positron emission tomography/CT-guided volumetric-modulated arc therapy-based dose escalation for hypoxic subvolume in nasopharyngeal carcinomas: A feasibility study.

The purpose of this study is to investigate the feasibility of a simultaneously integrated boost to the hypoxic subvolume of nasopharyngeal carcinomas (NCPs) under the guidance of 18 F-fluoromisonidazole (FMISO) positron emission tomography (PET)/CT using volumetric-modulated arc therapy (VMAT) and intensity-modulated radiotherapy (IMRT) techniques. Eight patients with NPC were treated with simultaneous integrated boost-IMRT (treatment plan named IMRT70) with dose prescriptions of 70 Gy, 66 Gy, 60 Gy, and 54 Gy to the gross tumor volume (GTV), positive neck nodes, the planning target volume (PTV), and the clinically negative neck, respectively. Based on the same datasets, experimental plans with the same dose prescription plus a dose boost of 14 Gy (an escalation of 20% of the prescription dose) to the hypoxic volume target contoured on the pretreatment 18 F-FMISO PET/CT imaging were generated using IMRT and VMAT techniques, respectively (represented by IMRT84 and VMAT84). Two or more arcs (approximately 2-2.5 arcs, totally rotating angle <1000 degrees) were used in VMAT plans and 9 equally separated fields in IMRT plans. Dosimetric parameters, total monitor units, and delivery time were calculated for comparative study of plan quality and delivery efficiency between IMRT84 and VMAT84. In experimental plans, hypoxic target volumes successfully received the prescribed dose of 84 Gy in compliance with other dose constraints with either the IMRT technique or the VMAT technique. In terms of the target coverage, dose homogeneity, and organs at risk (OAR) sparing, there was no statistically significant difference between the actual treatment plan of IMRT70 and experimental plans. The total monitor unit of VMAT84 (525.7 ± 39.8) was significantly less than IMRT70 (1171.5 ± 167; P = .001) and IMRT84 (1388.3 ± 151.0; P = .001) per fraction, with 55.1% and 62.1% reduction. The average machine delivery time was 3.5 minutes for VMAT plans in comparison with approximately 8 minutes for IMRT plans, resulting in a reduction factor of 56.2%. For experimental plans, the 3D gamma index average was over 98.0% with no statistical significant difference when a 3%/3 mm gamma passing rate criteria was used. With the guidance of 18 F-FMISO PET/CT imaging, dose escalation to hypoxic zones within NPC could be achieved and delivered efficiently with the VMAT technique in comparison with the IMRT technique.

Qiu J ，Lv B ，Fu M ，Wang X ，Zheng X ，Zhuo W ... -  《-》

Dosimetric comparison of distal esophageal carcinoma plans for patients treated with small-spot intensity-modulated proton versus volumetric-modulated arc therapies.

Esophageal carcinoma is the eighth most common cancer in the world. Volumetric-modulated arc therapy (VMAT) is widely used to treat distal esophageal carcinoma due to high conformality to the target and good sparing of organs at risk (OAR). It is not clear if small-spot intensity-modulated proton therapy (IMPT) demonstrates a dosimetric advantage over VMAT. In this study, we compared dosimetric performance of VMAT and small-spot IMPT for distal esophageal carcinoma in terms of plan quality, plan robustness, and interplay effects. 35 distal esophageal carcinoma patients were retrospectively reviewed; 19 patients received small-spot IMPT and the remaining 16 of them received VMAT. Both plans were generated by delivering prescription doses to clinical target volumes (CTVs) on phase-averaged 4D-CT's. The dose-volume-histogram (DVH) band method was used to quantify plan robustness. Software was developed to evaluate interplay effects with randomized starting phases for each field per fraction. DVH indices were compared using Wilcoxon rank-sum test. For fair comparison, all the treatment plans were normalized to have the same CTVhigh D95% in the nominal scenario relative to the prescription dose. In the nominal scenario, small-spot IMPT delivered statistically significantly lower liver Dmean and V30Gy[RBE] , lung Dmean , heart Dmean compared with VMAT. CTVhigh dose homogeneity and protection of other OARs were comparable between the two treatments. In terms of plan robustness, the IMPT and VMAT plans were comparable for kidney V18Gy[RBE] , liver V30Gy[RBE] , stomach V45Gy[RBE] , lung Dmean , V5Gy[RBE] , and V20Gy[RBE] , cord Dmax and D 0.03 c m 3 , liver Dmean , heart V20Gy[RBE] , and V30Gy[RBE] , but IMPT was significantly worse for CTVhigh D95% , D 2 c m 3 , and D5% -D95% , CTVlow D95% , heart Dmean , and V40Gy[RBE] , requiring careful and experienced adjustments during the planning process and robustness considerations. The small-spot IMPT plans still met the standard clinical requirements after interplay effects were considered. Small-spot IMPT decreases doses to heart, liver, and total lung compared to VMAT as well as achieves clinically acceptable plan robustness. Our study supports the use of small-spot IMPT for the treatment of distal esophageal carcinoma.

Liu C ，Bhangoo RS ，Sio TT ，Yu NY ，Shan J ，Chiang JS ，Ding JX ，Rule WG ，Korte S ，Lara P ，Ding X ，Bues M ，Hu Y ，DeWees T ，Ashman JB ，Liu W ... -  《Journal of Applied Clinical Medical Physics》