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Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial.

ABSTRACT: PURPOSE:Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance. PATIENTS AND METHODS:Eligible adult patients with brain metastases received HA-WBRT to 30 Gy in 10 fractions. Standardized cognitive function and quality-of-life (QOL) assessments were performed at baseline and 2, 4, and 6 months. The primary end point was the Hopkins Verbal Learning Test-Revised Delayed Recall (HVLT-R DR) at 4 months. The historical control demonstrated a 30% mean relative decline in HVLT-R DR from baseline to 4 months. To detect a mean relative decline ? 15% in HVLT-R DR after HA-WBRT, 51 analyzable patients were required to ensure 80% statistical power with ? = 0.05. RESULTS:Of 113 patients accrued from March 2011 through November 2012, 42 patients were analyzable at 4 months. Mean relative decline in HVLT-R DR from baseline to 4 months was 7.0% (95% CI, -4.7% to 18.7%), significantly lower in comparison with the historical control (P < .001). No decline in QOL scores was observed. Two grade 3 toxicities and no grade 4 to 5 toxicities were reported. Median survival was 6.8 months. CONCLUSION:Conformal avoidance of the hippocampus during WBRT is associated with preservation of memory and QOL as compared with historical series.

SUBMITTER: Gondi V

PROVIDER: S-EPMC4239303 | biostudies-literature | 2014 Dec

REPOSITORIES: biostudies-literature

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Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial.

Gondi Vinai V Pugh Stephanie L SL Tome Wolfgang A WA Caine Chip C Corn Ben B Kanner Andrew A Rowley Howard H Kundapur Vijayananda V DeNittis Albert A Greenspoon Jeffrey N JN Konski Andre A AA Bauman Glenn S GS Shah Sunjay S Shi Wenyin W Wendland Merideth M Kachnic Lisa L Mehta Minesh P MP

Journal of clinical oncology : official journal of the American Society of Clinical Oncology 20141027 34

<h4>Purpose</h4>Hippocampal neural stem-cell injury during whole-brain radiotherapy (WBRT) may play a role in memory decline. Intensity-modulated radiotherapy can be used to avoid conformally the hippocampal neural stem-cell compartment during WBRT (HA-WBRT). RTOG 0933 was a single-arm phase II study of HA-WBRT for brain metastases with prespecified comparison with a historical control of patients treated with WBRT without hippocampal avoidance.<h4>Patients and methods</h4>Eligible adult patient ...[more]

PMID: 25349290

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Project description:BackgroundRecent evidence supports hippocampal avoidance with whole brain radiotherapy (HA-WBRT) as the recommended treatment option in patients with good prognosis and multiple brain metastases as this results in better neurocognitive preservation compared to whole brain radiotherapy. However, there is often poor tumour control with this technique due to the low doses given. Stereotactic Radiosurgery (SRS), a form of focused radiotherapy which is given to patients who have a limited number of brain metastases, delivers a higher radiation dose to the metastases resulting in better target lesion control. With improvements in radiation technology, advanced dose-painting techniques now allow a simultaneous integrated boost (SIB) dose to lesions whilst minimising doses to the hippocampus to potentially improve brain tumour control and preserve cognitive outcomes. This technique is abbreviated to HA-SIB-WBRT or HA-WBRT+SIB.MethodsWe hypothesise that the SIB in HA-SIB-WBRT (experimental arm) will result in better tumour control compared to HA-WBRT (control arm). This may also lead to better intracranial disease control as well as functional and survival outcomes. We aim to conduct a prospective randomised phase II trial in patients who have good performance status, multiple brain metastases (4-25 lesions) and a reasonable life expectancy (> 6 months). These patients will be stratified according to the number of brain metastases and randomised between the 2 arms. We aim for a recruitment of 100 patients from a single centre over a period of 2 years. Our primary endpoint is target lesion control. These patients will be followed up over the following year and data on imaging, toxicity, quality of life, activities of daily living and cognitive measurements will be collected at set time points. The results will then be compared across the 2 arms and analysed.DiscussionPatients with brain metastases are living longer. Maintaining functional independence and intracranial disease control is thus increasingly important. Improving radiotherapy treatment techniques could provide better control and survival outcomes whilst maintaining quality of life, cognition and functional capacity. This trial will assess the benefits and possible toxicities of giving a SIB to HA-WBRT.Trial registrationClinicaltrials.gov identifier: NCT04452084 . Date of registration 30th June 2020.

Project description:BackgroundMelanoma brain metastases (MBM) often cause morbidity and mortality for stage IV melanoma patients. An ongoing randomised phase III trial (NCT01503827 - WBRT-Mel) evaluates the role of adjuvant whole brain radiotherapy (WBRT) following local treatment of MBM. Hippocampal avoidance during WBRT (HA-WBRT) has shown memory and neurocognitive function (NCF) preservation in the RTOG-0933 phase II study. This study assessed the quality assurance of HA-WBRT within the WBRT-Mel trial according to RTOG-0933 study criteria.MethodsHippocampal avoidance was allowed in approved centres with intensity-modulated radiotherapy capability. Patients treated by HA-WBRT were not randomized within the WBRT arm. The RTOG 0933 contouring Atlas was used to contour hippocampi. In the trial co-ordinating centre, patients were treated with volumetric modulated arc therapy using complementary arcs; similar techniques were used at other sites. Dosimetric data were extracted retrospectively and analysed in accordance with RTOG 0933 study constraints criteria.ResultsAmong the 215 patients accrued to the WBRT-Mel study between April 2009 and September 2017, 107 were randomized to the WBRT arm, 22 were treated by HA-WBRT in 4 centers. Eighteen patients were treated in the same centre. The median age was 65 years. The commonest (91%) HA-WBRT schema was 30 Gy in 10 fractions. Prior to HA-WBRT, 10 patients had been treated by surgery alone, six by radiosurgery alone, four by surgery and radiosurgery and two exclusively by simultaneous integrated boost concurrent to HA-WBRT. Twenty patients were treated with intention to spare both hippocampi and two patients had MBM close to one hippocampus and were treated with intention to spare the contralateral hippocampus. According to RTOG-0933 study criteria, 18 patients (82%) were treated within constraints and four patients (18%) had unacceptable deviation in just one hippocampus.ConclusionsThis dosimetric quality assurance study shows good compliance (82%) according to RTOG-0933 study dosimetric constraints. Indeed, all patients respected RTOG hippocampal avoidance constraints on at least one hippocampus. In the futureanalysis of the WBRT-Mel trial, the NCF of patients on the observation arm, WBRT arm and with HA-WBRT arm will be compared.

Project description:Hippocampal avoidance during whole-brain radiotherapy is performed to prevent neural stem cell injury causing neurocognitive dysfunction. Nevertheless, the estimated risk of metastases in hippocampal avoidance area in small-cell lung cancer is unknown. The current study aimed to characterize the metastatic distribution within the brain relative to the hippocampus, estimate the incidence of hippocampal metastasis in patients with small-cell lung cancer, and identify clinical and radiographic variables that may be associated with the risk of hippocampal avoidance area metastasis.Patients with small-cell lung cancer treated with therapeutic whole-brain radiotherapy between January 2010 and December 2015 were reviewed. T1-weighted, postcontrast axial magnetic resonance images obtained just before therapeutic cranial irradiation were retrieved and reviewed for each patient. The hippocampal avoidance area was defined as hippocampus and 5-mm ring area adjacent to the hippocampus to account for necessary dose falloff between the hippocampus and the whole-brain planning target volume. Metastatic lesions within hippocampal avoidance area were defined as hippocampal metastasis. Hippocampal metastasis rate and characteristics of patients with hippocampal metastasis were analyzed and compared to patients without hippocampal metastasis.Fifty-four patients evaluated with cranial magnetic resonance imaging were enrolled. Hippocampal metastasis rate was 32% (17 patients). A total of 4.4% of all metastases involved the hippocampal avoidance area. The most common location was frontal lobe. Being younger than 65 years of age was found to be an independent risk factor for HM (odds ratio: 4.8, 95% confidence interval: 1-23.2, P = .049). The number of brain metastases was significantly higher in patients with hippocampal metastasis ( P = .027), and hippocampal metastasis rate was also higher in patients having larger hippocampus ( P = .026) and larger brain volumes ( P = .02).Hippocampal metastasis might be more common in small-cell lung cancer. Reducing the dose to the hippocampus by hippocampal avoiding whole-brain radiotherapy plan in small-cell lung cancer may be risky for the development of HM compared with other malignant solid tumors.

Dataset Information

Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial.

Publications

Preservation of memory with conformal avoidance of the hippocampal neural stem-cell compartment during whole-brain radiotherapy for brain metastases (RTOG 0933): a phase II multi-institutional trial.

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