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 ... -  《-》

Esophageal cancer dose escalation using a simultaneous integrated boost technique.

We previously showed that 75% of radiation therapy (RT) failures in patients with unresectable esophageal cancer are in the gross tumor volume (GTV). We performed a planning study to evaluate if a simultaneous integrated boost (SIB) technique could selectively deliver a boost dose of radiation to the GTV in patients with esophageal cancer. Treatment plans were generated using four different approaches (two-dimensional conformal radiotherapy [2D-CRT] to 50.4 Gy, 2D-CRT to 64.8 Gy, intensity-modulated RT [IMRT] to 50.4 Gy, and SIB-IMRT to 64.8 Gy) and optimized for 10 patients with distal esophageal cancer. All plans were constructed to deliver the target dose in 28 fractions using heterogeneity corrections. Isodose distributions were evaluated for target coverage and normal tissue exposure. The 50.4 Gy IMRT plan was associated with significant reductions in mean cardiac, pulmonary, and hepatic doses relative to the 50.4 Gy 2D-CRT plan. The 64.8 Gy SIB-IMRT plan produced a 28% increase in GTV dose and comparable normal tissue doses as the 50.4 Gy IMRT plan; compared with the 50.4 Gy 2D-CRT plan, the 64.8 Gy SIB-IMRT produced significant dose reductions to all critical structures (heart, lung, liver, and spinal cord). The use of SIB-IMRT allowed us to selectively increase the dose to the GTV, the area at highest risk of failure, while simultaneously reducing the dose to the normal heart, lung, and liver. Clinical implications warrant systematic evaluation.

Welsh J ，Palmer MB ，Ajani JA ，Liao Z ，Swisher SG ，Hofstetter WL ，Allen PK ，Settle SH ，Gomez D ，Likhacheva A ，Cox JD ，Komaki R ... -  《-》

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 ... -  《-》

Volumetric modulation arc radiotherapy with flattening filter-free beams compared with static gantry IMRT and 3D conformal radiotherapy for advanced esophageal cancer: a feasibility study.

A feasibility study was performed to evaluate RapidArc (RA), and the potential benefit of flattening filter-free beams, on advanced esophageal cancer against intensity-modulated radiotherapy (IMRT) and three-dimensional conformal radiotherapy (3D-CRT). The plans for 3D-CRT and IMRT with three to seven and five to seven fixed beams were compared against double-modulated arcs with avoidance sectors to spare the lungs for 10 patients. All plans were optimized for 6-MV photon beams. The RA plans were studied for conventional and flattening filter-free (FFF) beams. The objectives for the planning target volume were the volume receiving ≥ 95% or at most 107% of the prescribed dose of <1% with a dose prescription of 59.4 Gy. For the organs at risk, the lung volume (minus the planning target volume) receiving ≥ 5 Gy was <60%, that receiving 20 Gy was <20%-30%, and the mean lung dose was <15.0 Gy. The heart volume receiving 45 Gy was <20%, volume receiving 30 Gy was <50%. The spinal dose received by 1% was <45 Gy. The technical delivery parameters for RA were assessed to compare the normal and FFF beam characteristics. RA and IMRT provided equivalent coverage and homogeneity, slightly superior to 3D-CRT. The conformity index was 1.2 ± 0.1 for RA and IMRT and 1.5 ± 0.2 for 3D-CRT. The mean lung dose was 12.2 ± 4.5 for IMRT, 11.3 ± 4.6 for RA, and 10.8 ± 4.4 for RA with FFF beams, 18.2 ± 8.5 for 3D-CRT. The percentage of volume receiving ≥ 20 Gy ranged from 23.6% ± 9.1% to 21.1% ± 9.7% for IMRT and RA (FFF beams) and 39.2% ± 17.0% for 3D-CRT. The heart and spine objectives were met by all techniques. The monitor units for IMRT and RA were 457 ± 139, 322 ± 20, and 387 ± 40, respectively. RA with FFF beams showed, compared with RA with normal beams, a ∼20% increase in monitor units per Gray, a 90% increase in the average dose rate, and 20% reduction in beam on time (owing to different gantry speeds). RA demonstrated, compared with conventional IMRT, a similar target coverage and some better dose sparing to the organs at risk; the advantage against conventional 3D-CRT was more evident. RA with FFF beams resulted in minor improvements in plan quality but with the potential for additional useful reduction in the treatment time.

Nicolini G ，Ghosh-Laskar S ，Shrivastava SK ，Banerjee S ，Chaudhary S ，Agarwal JP ，Munshi A ，Clivio A ，Fogliata A ，Mancosu P ，Vanetti E ，Cozzi L ... -  《-》

Comparison of heart and coronary artery doses associated with intensity-modulated radiotherapy versus three-dimensional conformal radiotherapy for distal esophageal cancer.

To compare heart and coronary artery radiation exposure using intensity-modulated radiotherapy (IMRT) vs. four-field three-dimensional conformal radiotherapy (3D-CRT) treatment plans for patients with distal esophageal cancer undergoing chemoradiation. Nineteen patients with distal esophageal cancers treated with IMRT from March 2007 to May 2008 were identified. All patients were treated to 50.4 Gy with five-field IMRT plans. Theoretical 3D-CRT plans with four-field beam arrangements were generated. Dose-volume histograms of the planning target volume, heart, right coronary artery, left coronary artery, and other critical normal tissues were compared between the IMRT and 3D-CRT plans, and selected parameters were statistically evaluated using the Wilcoxon rank-sum test. Intensity-modulated radiotherapy treatment planning showed significant reduction (p < 0.05) in heart dose over 3D-CRT as assessed by average mean dose (22.9 vs. 28.2 Gy) and V30 (24.8% vs. 61.0%). There was also significant sparing of the right coronary artery (average mean dose, 23.8 Gy vs. 35.5 Gy), whereas the left coronary artery showed no significant improvement (mean dose, 11.2 Gy vs. 9.2 Gy), p = 0.11. There was no significant difference in percentage of total lung volume receiving at least 10, 15, or 20 Gy or in the mean lung dose between the planning methods. There were also no significant differences observed for the kidneys, liver, stomach, or spinal cord. Intensity-modulated radiotherapy achieved a significant improvement in target conformity as measured by the conformality index (ratio of total volume receiving 95% of prescription dose to planning target volume receiving 95% of prescription dose), with the mean conformality index reduced from 1.56 to 1.30 using IMRT. Treatment of patients with distal esophageal cancer using IMRT significantly decreases the exposure of the heart and right coronary artery when compared with 3D-CRT. Long-term studies are necessary to determine how this will impact on development of coronary artery disease and other cardiac complications.

Kole TP ，Aghayere O ，Kwah J ，Yorke ED ，Goodman KA ... -  《-》