Hippocampal Avoidance Region Research Articles

限局期smallcell肺癌における海馬温存予防的全脳照射の一次臨床研究【Powered by NICT】

Objective To preliminarily observe the clinical efficacy of hippocampal-sparing prophylactic cranial irradiation (HS-PCI) using helical tomotherapy (HT) in patients with limited-stage small-cell lung cancer (LS-SCLC) after chemoradiotherapy, and compare HT with intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) in dose distribution. Methods From April to June, 2014, six patients with LS-SCLC who had achieved a complete remission after chemoradiotherapy were assigned to HS-PCI using HT within a month after brain metastasis was ruled out using brain magnetic resonance imaging (MRI). After fusing CT images and MRI images, the hippocampus was contoured in the fusion images and hippocampal avoidance regions were created using a volumetric expansion of 3 mm around the hippocampus. A dose of 25 Gy in 10 fractions to 95%of planning target volume (PTV) was prescribed in HT, IMRT, and VMAT. The clinical efficacy, adverse reactions, neurocognitive function, and brain metastasis were evaluated for HT. The dose distribution in PTV and hippocampus were compared between HT, IMRT, and VMAT. Results There were one patient with abdominal wall and abdominal lymph node metastases, one patient with local recurrence, and no patient with brain metastasis during the observation period. The numbers of patients with grade 1 and grade 2 headache, dizziness, and hair loss reactions were 3 and 1, 3 and 1, and 4 and 2, respectively. There were no significant differences in the average score of the Mini-Mental State Examination before treatment and at 3and 6 months after treatment (29.7, 29.2, and 29.3; P=0.083, 0.317, and 0.157). The mean dose to the hippocampus was 16.85 Gy for IMRT and 17.59 Gy for VMAT. For HT, the mean doses to the hippocampus and avoidance regions were reduced to 5.26 Gy and 6.21 Gy, respectively. The prescribed dose for HT was reduced by 79% and 71% compared with IMRT and VMAT, respectively. The average coverage rate of the prescribed dose was 94.48% for HT. Conclusions HT achieves promising dose distribution and target coverage in sparing of the hippocampus. Moreover, HT dose not increase the incidence of adverse reactions. The change in neurocognitive function needs to be further studied with long-term observation and large-scale sampling. Key words: Carcinoma, small-cell lung, limited stage; Hippocampal-sparing prophylactic cranial irradiation; Helical tomotherapy; Neurocognitive function; Three-dimensional radiotherapy; Dosimetry

Optimizing patient positioning for intensity modulated radiation therapy in hippocampal-sparing whole brain radiation therapy

PurposeSparing the hippocampus during whole brain radiation therapy (WBRT) offers potential neurocognitive benefits. However, previously reported intensity modulated radiation therapy (IMRT) plans use multiple noncoplanar beams for treatment delivery. An optimized coplanar IMRT template for hippocampal-sparing WBRT would assist in clinical workflow and minimize resource utilization. In this study, we sought to determine the optimal patient position to facilitate coplanar treatment planning and delivery of hippocampal-sparing WBRT using IMRT. Methods and materialsA variable angle, inclined board was utilized for patient positioning. An anthropomorphic phantom underwent computed tomography simulation at various head angles. The IMRT goals were designed to achieve target coverage of the brain while maintaining hippocampal dose–volume constraints designed to conform to the Radiation Therapy Oncology Group 0933 protocol. Optimal head angle was then verified using data from 8 patients comparing coplanar and noncoplanar WBRT IMRT plans. ResultsHippocampal, hippocampal avoidance region, and whole brain mean volumes were 1.1 cm3, 12.5 cm3, and 1185.1 cm3, respectively. The hippocampal avoidance region occupied 1.1% of the whole brain planning volume. For the 30-degree head angle, a 7-field coplanar IMRT plan was generated, sparing the hippocampus to a maximum dose of 14.7 Gy; D100% of the hippocampus was 7.4 Gy and mean hippocampal dose was 9.3 Gy. In comparison, for flat head positioning the hippocampal Dmax was 22.9 Gy with a D100% of 9.2 Gy and mean dose of 11.7 Gy. Target coverage and dose homogeneity was comparable with previously published noncoplanar IMRT plans. ConclusionsCompared with conventional supine positioning, an inclined head board at 30 degrees optimizes coplanar whole brain IMRT treatment planning. Clinically acceptable hippocampal-sparing WBRT dosimetry can be obtained using a simplified coplanar plan at a 30-degree head angle, thus obviating the need for complex and time consuming noncoplanar IMRT plans.

Can hippocampus be spared in patients with small cell lung carcinoma (SCLC) during cranial radiation therapy (CRT)?

7596 Background: Although CRT is a standard therapy for prevention and treatment of brain metastases (BM) in patients with SCLC, neurocognitive impairment (NI) following therapeutic whole brain radiation treatment (WBRT) or prophylactic cranial irradiation (PCI) is a major problem and can cause impairment in quality of life. A RTOG study is assessing various outcomes by avoiding the hippocampus (AH) during WBRT in different malignancies. The estimated risk of hippocampal avoidance region metastases (HM) in patients with SCLC before & after WBRT/PCI is not known. AH during CRT may delay the onset of NI in such patients. Our study aims to determine risk of HM in patients with SCLC and to assess clinical factors correlate with it. Methods: A patients cohort of SCLC diagnosed and treated at the Saskatoon Cancer Center between 2005 and 2012 were followed. All MRI and/or CT scans were independently reviewed by a neuroradiologist. HM was defined as BM within 5 mm of hippocampus. Binary Logistic regression analysis was done to assess correlation between various clinical variables and HM using SPSS. Results: 162 patients with SCLC were identified, 60 (37%) have developed BM. The preliminary data of 39/60 patients is presented here. All 39 patients received CRT and 17 patients received upfront chemotherapy. Their median age was 63 yrs (range: 41-82) & M:F was 22:17. 30 (77%) had extensive stage SCLC and 30 (77%) had de novo BM before CRT. A total 198 (range: 1-33) BM were identified among these patients with a mean BM of 6.6 per patient. 4 (13.3%) of 30 patients had HM involvement with mean BM of 1.3 per patient. Median follow up was 13.5 months (range: 1-69). Post-CRT 13 (33%) of 39 patients (4 PCI, 9 WBRT) developed central nervous system (CNS) progression. None of 13 patients with CNS failure following CRT developed HM. Overall 4 (10.2%) of 39 patients developed HM. No clinical factors significantly correlated with HM. Conclusions: The preliminary result revealed that overall incidence of HM before and after WBRT/PCI is low. AH in such patients may consider during CRT to avoid NI. The study is ongoing and final analysis will be presented.

Whole Brain Irradiation With Hippocampal Sparing and Dose Escalation on Multiple Brain Metastases: A Planning Study on Treatment Concepts

To develop a new treatment planning strategy in patients with multiple brain metastases. The goal was to perform whole brain irradiation (WBI) with hippocampal sparing and dose escalation on multiple brain metastases. Two treatment concepts were investigated: simultaneously integrated boost (SIB) and WBI followed by stereotactic fractionated radiation therapy sequential concept (SC). Treatment plans for both concepts were calculated for 10 patients with 2-8 brain metastases using volumetric modulated arc therapy. In the SIB concept, the prescribed dose was 30 Gy in 12 fractions to the whole brain and 51 Gy in 12 fractions to individual brain metastases. In the SC concept, the prescription was 30 Gy in 12 fractions to the whole brain followed by 18 Gy in 2 fractions to brain metastases. All plans were optimized for dose coverage of whole brain and lesions, simultaneously minimizing dose to the hippocampus. The treatment plans were evaluated on target coverage, homogeneity, and minimal dose to the hippocampus and organs at risk. The SIB concept enabled more successful sparing of the hippocampus; the mean dose to the hippocampus was 7.55±0.62 Gy and 6.29±0.62 Gy, respectively, when 5-mm and 10-mm avoidance regions around the hippocampus were used, normalized to 2-Gy fractions. In the SC concept, the mean dose to hippocampus was 9.8±1.75 Gy. The mean dose to the whole brain (excluding metastases) was 33.2±0.7 Gy and 32.7±0.96 Gy, respectively, in the SIB concept, for 5-mm and 10-mm hippocampus avoidance regions, and 37.23±1.42 Gy in SC. Both concepts, SIB and SC, were able to achieve adequate whole brain coverage and radiosurgery-equivalent dose distributions to individual brain metastases. The SIB technique achieved better sparing of the hippocampus, especially when a10-mm hippocampal avoidance region was used.

Optimizing Patient Positioning for Intensity Modulated Radiation Therapy in Hippocampal-Sparing Whole Brain Radiation Therapy

To determine the optimal patient position, using an inclined headboard, for treatment planning of hippocampal-sparing whole brain radiation therapy (WBRT) using intensity modulated radiation therapy (IMRT). Sparing the hippocampus during whole brain radiation therapy offers potential neurocognitive benefits over traditional WBRT. However, previously reported IMRT plans use multiple non-coplanar beams for treatment delivery. Given the possible widespread use of IMRT for WBRT, including an upcoming RTOG trial, an optimized coplanar IMRT template for hippocampal-sparing WBRT would assist in clinical workflow and also help minimize costs. A variable angle, inclined board with the ability to mount an Aquaplast mask was utilized for patient positioning. An anthropomorphic phantom underwent CT simulation at 0, 15, 30, and 40 degree angles. Contours of the brain, lenses of the eyes and hippocampus were generated and used as goal structures for IMRT planning. IMRT goals were designed to achieve target PTV coverage while maintaining a hippocampal D100% ≤ 9 Gy and maximum hippocampal dose ≤ 16 Gy. Planning was initially performed on the 30 degree data set using a coplanar beam arrangement to deliver 30 Gy in 10 fractions. The plan was optimized and then applied to the other head angles. Dose-volume histograms were reviewed with attention paid to D100%, maximum and mean dose to the hippocampus as well as the dose to the lenses. Volumes for the hippocampus, hippocampal avoidance region and whole brain were 1.07 cm3, 12.48 cm3 and 1185.1 cm3 respectively. The hippocampal avoidance region occupied 1.05% of the whole brain planning volume. For the 30 degree head angle, a 7 field IMRT plan utilizing a coplanar beam arrangement was generated sparing the hippocampus to a maximum dose of 14.67 Gy. D100% of the hippocampus was 7.37 Gy and mean hippocampal dose was 9.34 Gy. Similar values were obtained for the 15 degree head angle. In comparison, for flat head positioning the hippocampal Dmax was 22.91 Gy with a D100% of 9.18 Gy and mean dose of 11.7 Gy. Target coverage and dose homogeneity was comparable to previously published non-coplanar IMRT plans. Compared to conventional supine positioning, the use of an inclined head board at 15 or 30 degrees allows for optimal IMRT planning for a coplanar treatment plan. Acceptable dosimetry can be obtained for coplanar hippocampal-sparing whole brain radiation therapy with the addition of an inclined head board.

Hippocampal-Sparing Whole-Brain Radiotherapy: A “How-To” Technique Using Helical Tomotherapy and Linear Accelerator–Based Intensity-Modulated Radiotherapy

Sparing the hippocampus during cranial irradiation poses important technical challenges with respect to contouring and treatment planning. Herein we report our preliminary experience with whole-brain radiotherapy using hippocampal sparing for patients with brain metastases. Five anonymous patients previously treated with whole-brain radiotherapy with hippocampal sparing were reviewed. The hippocampus was contoured, and hippocampal avoidance regions were created using a 5-mm volumetric expansion around the hippocampus. Helical tomotherapy and linear accelerator (LINAC)-based intensity-modulated radiotherapy (IMRT) treatment plans were generated for a prescription dose of 30 Gy in 10 fractions. On average, the hippocampal avoidance volume was 3.3 cm(3), occupying 2.1% of the whole-brain planned target volume. Helical tomotherapy spared the hippocampus, with a median dose of 5.5 Gy and maximum dose of 12.8 Gy. LINAC-based IMRT spared the hippocampus, with a median dose of 7.8 Gy and maximum dose of 15.3 Gy. On a per-fraction basis, mean dose to the hippocampus (normalized to 2-Gy fractions) was reduced by 87% to 0.49 Gy(2) using helical tomotherapy and by 81% to 0.73 Gy(2) using LINAC-based IMRT. Target coverage and homogeneity was acceptable with both IMRT modalities, with differences largely attributed to more rapid dose fall-off with helical tomotherapy. Modern IMRT techniques allow for sparing of the hippocampus with acceptable target coverage and homogeneity. Based on compelling preclinical evidence, a Phase II cooperative group trial has been developed to test the postulated neurocognitive benefit.

Estimated risk of perihippocampal disease progression after hippocampal avoidance during whole-brain radiotherapy: Safety profile for RTOG 0933

Background and purpose RTOG 0933 is a phase II clinical trial of hippocampal avoidance during whole-brain radiotherapy (HA-WBRT) to prevent radiation-induced neurocognitive decline. By quantifying baseline incidence of perihippocampal or hippocampal metastasis, we sought to estimate the risk of developing metastases in the hippocampal avoidance region (the hippocampus plus 5 mm margin). Materials/methods Patients with ⩽10 brain metastases treated at two separate institutions were reviewed. Axial images from pre-treatment, post-contrast MRIs were used to contour each metastasis and hippocampus according to a published protocol. Clinical and radiographic variables were correlated with perihippocampal metastasis using a binary logistical regression analysis, with two-sided p < 0.05 for statistical significance. Results 1133 metastases were identified in 371 patients. Metastases within 5 mm of the hippocampus were observed in 8.6% of patients (95% CI 5.7–11.5%) and 3.0% of brain metastases. None of the metastases lay within the hippocampus. A 1-cm 3 increase in the aggregate volume of intra-cranial metastatic disease was associated with an odds ratio of 1.02 (95% CI 1.006–1.034, p = 0.003) for the presence of perihippocampal metastasis. Conclusion With an estimated perihippocampal metastasis risk of 8.6%, we deem HA-WBRT safe for clinical testing in patients with brain metastases as part of RTOG 0933.

Estimated Risk of Perihippocampal Disease Progression after Hippocampal Avoidance during Whole-brain Radiotherapy: Comprehensive Multi-institution Review of 371 Patients with 1133 Brain Metastases

No patients had a metastasis within the hippocampus. A 1-cm 3 increase in the aggregate volume of intracranial metastatic disease was associated with an odds ratio of 1.02 (95% CI 1.006-1.034, p = 0.003) for the presence of perihippocampal metastasis. Aggregate intracranial disease volumes of 1-cm 3 , 10-cm 3 , and 35-cm 3 were associated with estimated incidences of perihippocampal metastasis of 6.4%, 7.5%, and 11.8%, respectively. The remaining clinical and radiographic variables, including number of intracranial metastases, were not predictive. Conclusions:If we assume that the risk of development of a subsequent brain metastasis within the hippocampal avoidance region scales in the same proportion as that at presentation, we conclude that a patient treated with HA-WBRT will derive 91.4% of the relative benefit of WBRT in terms of preventionof the emergenceof radiographically visible intracranial lesions,with a lower 95% confidence limit of 88.5%. Intracranial volume of metastatic disease, but not number of metastases, predicts for increased risk of developing perihippocampal metastases.

CE test

Sparing the hippocampus during whole brain radiation therapy (WBRT) offers potential neurocognitive benefits. However, previously reported intensity modulated radiation therapy (IMRT) plans use multiple noncoplanar beams for treatment delivery. An optimized coplanar IMRT template for hippocampal-sparing WBRT would assist in clinical workflow and minimize resource utilization. In this study, we sought to determine the optimal patient position to facilitate coplanar treatment planning and delivery of hippocampal-sparing WBRT using IMRT.A variable angle, inclined board was utilized for patient positioning. An anthropomorphic phantom underwent computed tomography simulation at various head angles. The IMRT goals were designed to achieve target coverage of the brain while maintaining hippocampal dose–volume constraints designed to conform to the Radiation Therapy Oncology Group 0933 protocol. Optimal head angle was then verified using data from 8 patients comparing coplanar and noncoplanar WBRT IMRT plans.Hippocampal, hippocampal avoidance region, and whole brain mean volumes were 1.1 cm3, 12.5 cm3, and 1185.1 cm3, respectively. The hippocampal avoidance region occupied 1.1% of the whole brain planning volume. For the 30-degree head angle, a 7-field coplanar IMRT plan was generated, sparing the hippocampus to a maximum dose of 14.7 Gy; D100% of the hippocampus was 7.4 Gy and mean hippocampal dose was 9.3 Gy. In comparison, for flat head positioning the hippocampal Dmax was 22.9 Gy with a D100% of 9.2 Gy and mean dose of 11.7 Gy. Target coverage and dose homogeneity was comparable with previously published noncoplanar IMRT plans.Compared with conventional supine positioning, an inclined head board at 30 degrees optimizes coplanar whole brain IMRT treatment planning. Clinically acceptable hippocampal-sparing WBRT dosimetry can be obtained using a simplified coplanar plan at a 30-degree head angle, thus obviating the need for complex and time consuming noncoplanar IMRT plans.