Whole Brain Radiotherapy In Patients Research Articles

A matched-pair analysis comparing stereotactic radiosurgery with whole-brain radiotherapy for patients with multiple brain metastases

Stereotactic radiosurgery (SRS) is an emerging treatment for patients with multiple brain metastases (BM). The present work compares the SRS of multiple brain metastases with whole-brain radiotherapy (WBRT). We performed a matched-pair analysis for 128 patients with multiple BM treated with either SRS or WBRT over a 5-year period. Patients were matched pairwise for seven potential prognostic factors. A mixed Cox Proportional Hazards model with univariate and multivariate analysis was fitted for overall survival (OS).Distant intracranial progression-free survival (icPFS) and local control were assessed using a Fine and Gray subdistribution hazard model and considering death as competing event. Patients undergoing SRS had a median of 4 BM (range 3-16). 1-year local control of individual BM following SRS was 91.7%. Median OS in the SRS subgroup was 15.7months (IQR 9.7-36.4) versus 8.0months (interquartile range, IQR 3.8-18.0) in the WBRT subgroup (HR 2.25, 95% CI [1.5; 3.5], p<0.001). Median icPFS was 8.6 (IQR 3.4-18.0) versus 22.4 (IQR 5.6-28.6) months, respectively (HR for WBRT 0.41, 95% CI [0.24; 0.71], p=0.001). Following SRS, synchronous BM diagnosis (HR 2.51, 95% CI [1.30; 4.70], p=0.004), higher initial number of BM (HR 1.21, 95% CI [1.10; 1.40], p=0.002) and lung cancer histology (HR 2.05, 95% CI [1.10; 3.80], p=0.024) negatively impacted survival. Excellent clinical performance (KPI 90%) was a positive prognosticator (HR 0.38, 95% CI [0.20; 0.72], p=0.003), as was extracerebral tumor control (HR 0.48, 95% CI [0.24; 0.97], p=0.040). Higher initial (HR 1.19, 95% CI [1.00; 1.40], p<0.013) and total number of BM (HR 1.23, 95% CI [1.10; 1.40], p<0.001) were prognostic for shorter icPFS. This is the first matched-pair analysis to compare SRS alone versus WBRT alone for multiple BM. OS was prolonged in the SRS subgroup and generally favorable in the entire cohort. Our results suggest SRS as a feasible and effective treatment for patients with multiple BM.

Whole brain radiotherapy improves survival outcomes in primary CNS lymphoma patients ineligible for systemic therapy

Primary central nervous system lymphoma (PCNSL) is a very rare type of malignancy with a poor prognosis. The role of whole brain radiotherapy (WBRT) in PCNSL has been questioned due to the significant neurotoxicity and lack of convincing data for survival benefit. Even its role in a palliative setting remains to be clearly elucidated. Our study aims to investigate the benefit of WBRT in patients who are ineligible for systemic therapy. A single-institution retrospective study was conducted on patients diagnosed with PCNSL between 2002 and 2017. Patients were excluded if they received systemic therapy or focal radiation only. Data on patient demographics and WBRT were collected and correlated with clinical outcomes. A total of 48 patients were selected for analysis, among which 31 (64.6%) patients received WBRT and 17 (35.4%) patients received supportive care only. Patient baseline characteristics were similar between the two groups. Median overall survival (OS) was 4.3months among the entire cohort. WBRT was associated with improved median OS (8.0months, range 1.4-62.3months) compared with supportive care only (3.3months, range 0.7-18.3months) (HR 0.39, 95% CI 0.20-0.75, p = 0.005). Among patients who received WBRT, higher radiation dose to the whole brain was not associated with survival (p = 0.10), but higher radiation dose to the gross tumor was associated with improved survival (p = 0.007). Patients with PCNSL who are ineligible for systemic therapy may still benefit from WBRT with improvement in survival, compared with the best supportive care. Dose escalation through the addition of a gross tumor boost in these patients was associated with improved overall survival. Further studies in the prospective setting are necessary to confirm the findings from the study.

Preservation of long-term neurocognitive function by hippocampal avoidance whole-brain radiotherapy in patients with brain metastases.

124 Background: To investigate the preservation of long-term neurocognitive function in patients after hippocampal avoidance whole-brain radiotherapy (HA-WBRT). Methods: For the retrospective analysis, 50 patients diagnosed with brain metastases were selected and divided into two groups from 2015-01-01 to 2017-12-31 at the Department of Oncology, Jiangsu Subei People's Hospital. Group A (n=27) was hippocampal avoidance whole-brain radiotherapy group; group B (n=23) was whole brain radiation therapy (WBRT) group. Neurocognitive function was statistically analyzed at 3, 6, 9, 12, and 24 months after radiotherapy, as scored by the MMSE (Mine-Mental State Examination) scales and the MoCA (Montreal Cognitive Assessment) scales. The OS, PFS and tumor recurrence sites of the two groups was also analyzed. Results: After 12, 24 months after radiotherapy, there was a significant difference between the two groups. The cognitive function of the hippocampal protection group was significantly higher than that of the non-hippocampal protection group (P&lt;0.05). There was no significant difference in OS (P=0.2) and PFS (P=0.18) between the two groups. 14 patents in group A and 12 patents in group B had brain tumor recurrence after radiation, only one patient in group A occurred 5 mm within the edge of the hippocampus (P&gt;0.05). Conclusions: First, HA-WBRT has a protective effect on long-term neurocognitive function. Second, there was no statistically significant different on OS and PFS in patients who underwent HA-WBRT or WBRT. Third, HA-WBRT didn’t increase the risk of brain tumor recurrence within the edge of the hippocampus.

P2.01-34 Endostar Combined with Whole Brain Radiotherapy in Patients with NSCLC Brain Metastases

P2.01-34 Endostar Combined with Whole Brain Radiotherapy in Patients with NSCLC Brain Metastases

Supportive Care With or Without Repeated Whole Brain Radiotherapy in Patients With Recurrent Brain Metastases

Supportive Care With or Without Repeated Whole Brain Radiotherapy in Patients With Recurrent Brain Metastases

Combination of Whole-Brain Radiotherapy with Epidermal Growth Factor Receptor Tyrosine Kinase Inhibitors Improves Overall Survival in EGFR-Mutated Non-Small Cell Lung Cancer Patients with Brain Metastases.

Brain metastases (BM) cause morbidity and mortality in patients with non-small cell lung cancer (NSCLC). The use of upfront epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors (TKIs) and withholding of whole-brain radiation therapy (WBRT) is controversial. We aim to investigate the impact of WBRT on overall survival (OS). After screening 1384 patients, a total of 141 EGFR-mutated patients with NSCLC and BM were enrolled. All patients received EGFR-TKIs between 2011 and 2015. Ninety-four patients (66.7%) were treated with WBRT (TKI + WBRT group). With a median follow-up of 20.3 months (95% confidence interval (CI), 16.9–23.7), the median OS after the diagnosis of BM was 14.3 months (95% CI, 9.5 to 18.3) in the TKI + WBRT group and 2.3 months (95% CI, 2 to 2.6) in the TKI alone group. On multivariate analysis, WBRT (p < 0.001), female, surgery to primary lung tumor, and surgery to BM were associated with improved OS. The 1-year OS rate was longer in the TKI+WBRT group than that in the TKI alone group (81.9% vs. 59.6%, p = 0.002). In conclusion, this is the first study to demonstrate the negative survival impact from the omission of WBRT in patients with EGFR-mutant NSCLC.

NRG Oncology CC003: A randomized phase II/III trial of prophylactic cranial irradiation with or without hippocampal avoidance for small cell lung cancer.

TPS8578 Background: Multiple clinical trials have shown that prophylactic cranial irradiation (PCI) prevents brain metastases and may prolong survival in small cell lung cancer (SCLC). However,prophylactic cranial irradiation can lead to decline in cognitive function. Preclinical evidence suggests that the pathogenesis of this toxicity includes inflammatory injury to proliferating neuronal progenitor cells in the peri-hippocampal stem cell niches. We hypothesized that conformal avoidance of the hippocampal neural stem cell compartment during brain irradiation using intensity-modulated radiotherapy (IMRT) would decrease the likelihood and/or severity of this toxicity. This hypothesis was recently validated by positive results from NRG Oncology CC001, a phase III trial of hippocampal avoidance during whole-brain radiotherapy for patients with brain metastases. NRG Oncology CC003 is an ongoing randomized phase II/III trial of hippocampal avoidance during prophylactic cranial irradiation (HA-PCI) for small cell lung cancer, conducted in parallel with NRG Oncology CC001. Methods: The primary endpoints of the phase IIR and III components are 12-month intracranial relapse rate and 6-month deterioration in Hopkins Verbal Learning Test-Revised (HVLT-R) Delayed Recall, respectively. This is a seamless phase IIR/III trial, with the phase IIR designed to demonstrate non-inferiority. If the non-inferiority margin of the phase IIR component is not exceeded, then the trial would transition to the phase III component. Following accrual of 182 of planned 172 patients on the phase IIR component, the trial closed to accrual on 10/13/17 to assess the phase IIR primary endpoint. The DSMB evaluated the IIR outcomes, and on 1/9/19, the trial was reactivated to accrue an additional 122 patients to the phase III component. Eligibility criteria include: 1) small cell lung cancer with at least partial response to chemotherapy; 2) contrast-enhanced thin-slice volumetric MRI scan; and, 3) Zubrod performance status 0-2. Supported by grant UG1CA189867 (NCORP) from the National Cancer Institute. Clinical trial information: NCT02635009.

Local tumor progression treated with Gamma Knife radiosurgery: differences between patients with 2-4 versus 5-10 brain metastases based on an update of a multi-institutional prospective observational study (JLGK0901).

The Japanese Leksell Gamma Knife (JLGK)0901 study proved the efficacy of Gamma Knife radiosurgery (GKRS) in patients with 5-10 brain metastases (BMs) as compared to those with 2-4, showing noninferiority in overall survival and other secondary endpoints. However, the difference in local tumor progression between patients with 2-4 and those with 5-10 BMs has not been sufficiently examined for this data set. Thus, the authors reappraised this issue, employing the updated JLGK0901 data set with detailed observation via enhanced MRI. They applied sophisticated statistical methods to analyze the data. This was a prospective observational study of 1194 patients harboring 1-10 BMs treated with GKRS alone. Patients were categorized into groups A (single BM, 455 cases), B (2-4 BMs, 531 cases), and C (5-10 BMs, 208 cases). Local tumor progression was defined as a 20% increase in the maximum diameter of the enhanced lesion as compared to its smallest documented maximum diameter on enhanced MRI. The authors compared cumulative incidence differences determined by competing risk analysis and also conducted propensity score matching. Local tumor progression was observed in 212 patients (17.8% overall, groups A/B/C: 93/89/30 patients). Cumulative incidences of local tumor progression in groups A, B, and C were 15.2%, 10.6%, and 8.7% at 1 year after GKRS; 20.1%, 16.9%, and 13.5% at 3 years; and 21.4%, 17.4%, and not available at 5 years, respectively. There were no significant differences in local tumor progression between groups B and C. Local tumor progression was classified as tumor recurrence in 139 patients (groups A/B/C: 68/53/18 patients), radiation necrosis in 67 (24/31/12), and mixed/undetermined lesions in 6 (1/5/0). There were no significant differences in tumor recurrence or radiation necrosis between groups B and C. Multivariate analysis using the Fine-Gray proportional hazards model revealed age < 65 years, neurological symptoms, tumor volume ≥ 1 cm3, and prescription dose < 22 Gy to be significant poor prognostic factors for local tumor progression. In the subset of 558 case-matched patients (186 in each group), there were no significant differences between groups B and C in local tumor progression, nor in tumor recurrence or radiation necrosis. Local tumor progression incidences did not differ between groups B and C. This study proved that tumor progression after GKRS without whole-brain radiation therapy for patients with 5-10 BMs was satisfactorily treated with the doses prescribed according to the JLGK0901 study protocol and that results were not inferior to those in patients with a single or 2-4 BMs.Clinical trial registration no.: UMIN000001812 (umin.ac.jp).

Comparison between stereotactic radiosurgery and whole-brain radiotherapy for 10-20 brain metastases from non-small cell lung cancer.

The efficacy and safety of stereotactic radiosurgery (SRS) in comparison with whole brain radiotherapy (WBRT) for brain metastases (BMs) remains unclear. The present study retrospectively reviewed 44 patients who received SRS or WBRT as an initial treatment for 10-20 BMs from non-small cell lung cancer between 2009 and 2016. Of the patients, 24 (54.5%) were treated with SRS and 20 (45.5%) were treated with WBRT. Overall survival (OS), time to intracranial progression (TTIP), neurological survival (NS), and prognostic factors were examined. OS did not significantly differ between the two groups: 7.3 months in the SRS group vs. 7.2 months in the WBRT group (P=0.502). Median TTIP was significantly shorter in the SRS group than in the WBRT group (7.1 vs. 19.1 months, P=0.009). In contrast, there were no significant differences in NS between the two groups (14.5 months in the SRS group vs. 12.9 months in the WBRT group, P=0.346). Univariate and multivariate analysis revealed that the type of initial treatment for BMs (WBRT or SRS) was not a significant prognostic factor (hazard ratio=0.80, 95% confidence interval: 0.42-1.52, P=0.502). However, histology, performance status, subsequent molecular targeted drugs, subsequent chemotherapy and salvage treatment were independent prognostic factors. There were no significant differences in OS and NS between treatment with SRS and treatment with WBRT in patients with 10-20 BMs, although TTIP was improved with WBRT. As an upfront treatment for 10-20 BMs, SRS may delay WBRT and the adverse events associated with WBRT.

Potential Impact of the Interval Between Imaging and Whole-brain Radiotherapy in Patients With Relatively Favorable Survival Prognoses.

The interval between diagnostic imaging and whole-brain radiotherapy (WBRT) had no significant impact on survival in our previous study of WBRT for brain metastases. Since median survival time was only 2 months, a potentially negative impact by delaying treatment could have been missed. Therefore, we performed an additional analysis of patients surviving at least 4 months following irradiation. The interval between diagnosis of brain metastases and WBRT and ten other factors were retrospectively analyzed for survival in 191 patients surviving 4 months or longer following WBRT. On univariate analyses, Eastern Cooperative Oncology Group (ECOG) performance score of 0-1, 1-3 brain metastases and absence of extra-cerebral metastases were significantly associated with longer survival, whereas the interval from diagnostic imaging to WBRT was not. On multivariate analysis, ECOG performance score remained significant, and extra-cerebral metastases showed a trend towards a longer survival. The interval between diagnostic imaging and WBRT didn't have a significant impact on patients surviving 4 months or longer. Depending on the need for symptom relief, WBRT may be postponed for very important reasons such as obtaining a multidisciplinary tumor board decision or definitive histology.

Management of patients with brain metastases from non-small cell lung cancer and adverse prognostic features: multi-national radiation treatment recommendations are heterogeneous

BackgroundDifferent management options exist for patients with brain metastases from non-small cell lung cancer (NSCLC), patients whose treatment with whole brain radiotherapy (WBRT) has become more controversial over the last decade. It is not trivial to find the optimal balance of over- versus undertreatment in these patients. Several recent trials, including the randomized QUARTZ trial now influence the decision to recommend or withhold WBRT for patients with unfavorable prognosis, and similarly, for favorable prognosis patients, the balance between radiosurgery alone or WBRT has become a nuanced decision. Additionally, the availability of intracranially active targeted agent for some subsets of these patients has added another layer of complexity to the decision-making.MethodsA multinational consortium of expert radiation oncologists was established with the aim of compiling treatment recommendations for challenging scenarios, in this case the choice between optimal supportive care (SC), WBRT and other types of radiation therapy (RT). We distributed 17 cases to 7 radiation oncologists who were allowed to involve coworkers to provide their treatment recommendations. The cases differed in extra- and intracranial disease extent, histology, age and other prognostic factors. Expert recommendations were tabulated with the aim of providing guidance.ResultsRegarding willingness to include the 17 patients in the QUARTZ trial, the rates of trial inclusion were low (range 0/7 to 3/7). Experts not recommending trial inclusion provided their treatment recommendations. These suggestions differed widely for most of the patients. It was not uncommon to see 3 or 4 different recommendations. In general, few (0–2) recommended SC. Some kind of local treatment was suggested by the majority of experts for all 17 patients. Commonly, stereotactic single-fraction radiosurgery (SRS) or stereotactic fractionated radiotherapy (SFRT) were recommended by many experts, also for patients with 5–7 lesions. The highest proportion of recommendations towards WBRT in any patient was 3/7. It was also quite common for patients with multiple metastases of varying size that experts suggested combinations of resection, post-operative SRS/SFRT and SRS/SFRT to intact lesions. Despite recommending active treatment, experts were often willing to include the patients in a hypothetical protocol investigating radiotherapy utilization in the last 30 days of life (assessment of factors predicting early death).ConclusionsWBRT was infrequently recommended. Even in patients with adverse prognostic features that raised the experts’ awareness of an increased risk for futile treatment near the end of life, SRS/SFRT were more often recommended than optimal supportive care, unless a patient decided to forego active treatment.

Gamma knife-based stereotactic radiosurgery boost after whole-brain radiotherapy in patients with up to three brain metastases: Effects on survival, functional independence, and neurocognitive function

Background: Brain metastases are a major cause of mortality and morbidity in cancer patients and are seen as a terminal event in the natural course of disease. Whole-brain radiotherapy (WBRT) has remained the most commonly used treatment for multiple metastases. Although it provides symptomatic relief, the effects have low durability and local failure is common. Stereotactic radiosurgery (SRS) techniques such as Gamma Knife have been shown to be as effective as surgery in control of limited (1–3) metastases. Aim: The aim of this is to study the role of SRS boost after WBRT in patients of 1–3 brain metastases. Objective: (1) To compare the survival of patients with 1–3 brain metastases treated with WBRT with versus without SRS boost. (2) To compare the duration of functional independence (FI) and normal neurocognitive function (NNF) posttreatment in the patients belonging to the two groups. Materials and Methods: Twenty-six patients with 1–3 brain metastases received WBRT to a dose of 30 Gy in 10 fractions. Half the patients (13) were also given an SRS boost of 16–20 Gy by the Gamma Knife technique. All patients were followed up at twelve weekly intervals for a period of 9 months and assessed for survival, FI (Karnofsky Performance Status Score (KPS) >60%) and NNF (Hindi Mental Status Examination Score >24). Results: At 9 months, the median survival in the SRS boost group was 27 weeks compared to 22 weeks in the no boost group. The mean duration of FI and NNF was 24 and 12 weeks in the boost and nonboost groups, respectively. The differences between two groups were not statistically significant. Conclusions: Although results are not significant, a definite trend toward improvement in median survival, FI, and neurocognitive function in patients who received an SRS boost after WBRT is seen.

P2.01-127 Efficacy of Endostar Combined with Whole Brain Radiotherapy in Patients with NSCLC Brain Metastases

P2.01-127 Efficacy of Endostar Combined with Whole Brain Radiotherapy in Patients with NSCLC Brain Metastases

Prospective memory impairment following whole brain radiotherapy in patients with metastatic brain cancer.

ObjectiveTo investigate the prospective memory (PM) impairment following whole brain radiotherapy (WBRT) in cancer patients with brain metastases.MethodEighty‐one patients with metastatic brain cancer, agreeing to undergo WBRT, were enrolled and subjected to a battery of cognitive neuropsychological tests, including the mini‐mental state examination (MMSE), verbal fluency test (VFT), digit span test (DST), and event‐based and time‐based prospective memory (EBPM and TBPM) tasks, before and after radiotherapy.ResultsThe patients with metastatic brain cancer after WBRT exhibited a significant decrease in the MMSE, DST, VFT, and EBPM scores (t = 6.258, 10.192, 5.361, −5.892, P < 0.01), but nonsignificant decrease in the TBPM scores (t = −1.172, P > 0.05).ConclusionThere is significant EBPM impairment in cancer patients with brain metastases after WBRT, whereas that in the TBPM remained relatively unaffected. The result suggests that EBPM impairment may be as an early cognitive impairment marker in patients with BM who undergo WBRT.

Preservation of cognitive function following whole brain radiotherapy in patients with brain metastases: Complications, treatments, and the emerging role of memantine.

Whole brain radiotherapy is the mainstay of treatment for patients suffering from stage IV malignancies that have metastasized to the brain. Although this therapy is often effective at reducing tumor size and burden, it is associated with a spectrum of toxicities that often result in irreversible cognitive decline. Various drug and non-drug therapies have been evaluated to treat this neurotoxicity after whole brain radiotherapy is administered; however, currently available options have shown little benefit or come with side effects themselves that may outweigh the benefits of their use. For this reason, current investigations are focusing on preventing cognitive decline, rather than attempting to attenuate symptoms after they occur. Memantine has consistently shown promise in both in-vitro and in-vivo studies as a neuroprotective agent that may improve cognitive outcomes in patients undergoing whole brain radiotherapy. Memantine use prior to and during whole brain radiotherapy has been shown to significantly delay time to cognitive failure and reduce the rate of decline in memory, cognitive function, and processing speed. Its use has also been linked to significant decreases in brain edema, brain infarct size, and brain vasculature changes following whole brain radiotherapy. Memantine offers a promising safety profile with high tolerability and limited side effects. The objective of this article is to provide an overview of the target patient population, the neurotoxic effects of WBRT, current treatment options, and a summary of the available literature surrounding the use of memantine in this setting.

Effects of Surgery With Salvage Stereotactic Radiosurgery Versus Surgery With Whole-Brain Radiation Therapy in Patients With One to Four Brain Metastases (JCOG0504): A Phase III, Noninferiority, Randomized Controlled Trial

Purpose Whereas whole-brain radiotherapy (WBRT) has been the standard treatment of brain metastases (BMs), stereotactic radiosurgery (SRS) is increasingly preferred to avoid cognitive dysfunction; however, it has not been clearly determined whether treatment with SRS is as effective as that with WBRT or WBRT plus SRS. We thus assessed the noninferiority of salvage SRS to WBRT in patients with BMs. Patients and Methods Patients age 20 to 79 years old with performance status scores of 0 to 2-and 3 if caused only by neurologic deficits-and with four or fewer surgically resected BMs with only one lesion > 3 cm in diameter were eligible. Patients were randomly assigned to WBRT or salvage SRS arms within 21 days of surgery. The primary end point was overall survival. A one-sided α of .05 was used. Results Between January 2006 and May 2014, 137 and 134 patients were enrolled in the WBRT and salvage SRS arms, respectively. Median overall survival was 15.6 months in both arms (hazard ratio, 1.05; 90% CI, 0.83 to 1.33; one-sided P for noninferiority = .027). Median intracranial progression-free survival of patients in the WBRT arm (10.4 months) was longer than that of patients in the salvage SRS arm (4.0 months). The proportions of patients whose Mini-Mental Status Examination and performance status scores that did not worsen at 12 months were similar in both arms; however, 16.4% of patients in the WBRT arm experienced grade 2 to 4 cognitive dysfunction after 91 days postenrollment, whereas only 7.7% of those in the SRS arm did ( P = .048). Conclusion Salvage SRS is noninferior to WBRT and can be established as a standard therapy for patients with four or fewer BMs.

Efficacy and safety of endostar combined with whole brain radiotherapy in patients with NSCLC brain metastases.

e14002Background: Brain metastasis (BM) is the leading cause of poor prognosis, recurrence, and death in non-small-cell lung cancer (NSCLC) patients. Due to the limitation of the Blood-Brain Barrie...

Quality of life and efficacy of temozolomide combined with whole-brain radiotherapy in patients with brain metastases from non-small-cell lung cancer

The aim of the present study was to investigate the efficacy and life quality of temozolomide (TMZ) combined with whole-brain radiotherapy (WBRT) for patients with brain metastases (BM) from non-small-cell lung cancer (NSCLC). A total of 77 cases of patients with lung cancer and BM were selected and divided into two groups; the first group was administered WBRT with TMZ, and the second group was administered WBRT with placebo. The efficacy, overall survival (OS) and quality of life (QoL) were then compared between the two groups. There were no significant differences in toxicity between the two groups. However, the first group exhibited an advantage over the second group in terms of objective response and OS (P<0.5). Therefore, WBRT may improve the QoL of patients with BM. TMZ concomitantly with WBRT was well-tolerated and may be recommended for the treatment of BM from NSCLC.

A randomised trial to compare cognitive outcome after gamma knife radiosurgery versus whole brain radiation therapy in patients with multiple brain metastases: research protocol CAR-study B

BackgroundGamma Knife radiosurgery (GKRS) is increasingly applied in patients with multiple brain metastases and is expected to have less adverse effects in cognitive functioning than whole brain radiation therapy (WBRT). Effective treatment with the least negative cognitive side effects is increasingly becoming important, as more patients with brain metastases live longer due to more and better systemic treatment options. There are no published randomized trials yet directly comparing GKRS to WBRT in patients with multiple brain metastases that include objective neuropsychological testing.MethodsCAR-Study B is a prospective randomised trial comparing cognitive outcome after GKRS or WBRT in adult patients with 11–20 newly diagnosed brain metastases on a contrast-enhanced MRI-scan, KPS ≥70 and life expectancy of at least 3 months. Randomisation by the method of minimization, is stratified by the cumulative tumour volume in the brain, systemic treatment, KPS, histology, baseline cognitive functioning and age. The primary endpoint is the between-group difference in the percentage of patients with significant memory decline at 3 months.Secondary endpoints include overall survival, local control, development of new brain metastases, cognitive functioning over time, quality of life, depression, anxiety and fatigue. Cognitive functioning is assessed by a standardised neuropsychological test battery.Assessments (cognitive testing, questionnaires and MRI-scans) are scheduled at baseline and at 3, 6, 9, 12 and 15 months after treatment.DiscussionKnowledge gained from this trial may be used to inform individual patients with BM more precisely about the cognitive effects they can expect from treatment, and to assist both doctors and patients in making (shared) individual treatment decisions. This trial is currently recruiting. Target accrual: 23 patients at 3-months follow-up in both groups.Trial registrationThe Netherlands Trials Register number NTR5463. ClinicalTrials.gov registration number NCT02953717, first received October 27, 2016, 8 patients were enrolled in this study on 31 July 2017.

Abstract P1-17-06: Outcomes of central nervous system radiotherapy for metastatic breast cancer: The Royal Marsden experience 2000 - 2016

Abstract Background: Breast cancer (BC) is one of the most common malignancies affecting women. Brain metastatses (BM) are frequently seen in BC, and can have devastating consequences with significant associated morbidity and mortality. Whole brain radiotherapy (WBRT) is commonly used to treat BM, with variable use of stereotactic radiotherapy (SRT). This study reports on the outcomes of BC patients with BM who received central nervous system (CNS) radiotherapy over a 17-year period at the Royal Marsden Hospital (RMH). Methods: We included all BC patients who had WBRT with or without SRT for intra-parenchymal BM secondary to BC at RMH between 2000 and 2016 inclusive. Instances of meningeal involvement were excluded from analysis. Data collected included age, histological subtype, tumor grade, stage at original BC presentation, receptor status, date of BM diagnosis, number of metastases, size of largest BM, Eastern Cooperative Oncology Group (ECOG) score, presence of extra-cranial metastases (ECM), neurosurgery (NS) and stereotactic radiotherapy (SRT) details, and date of last follow up or death. Univariate and multivariate analyses were performed to analyze the effect of each variable on overall survival (OS) from date of BM. Results: A total of 426 patients were included with a median age of 54 years at BM diagnosis and a median time to BM from BC diagnosis of 43 months. At diagnosis, 94% had invasive ductal carcinoma (IDC) and 70% had Grade 3 disease. Stage IV disease at original BC presentation was seen in 18% of patients. Estrogen receptor (ER+) was positive in 57% (n = 236), progesterone receptor (PR+) in 44% (n = 147), and HER2 (HER2+) in 44% (n = 166). Twenty-two percent (n = 89) were triple negative (TN). Median number of BM was 4 (range 1 – 205) and 20% (n = 72) of patients had only 1 BM. Average size of the largest lesion was 26 mm (range 1 – 75). The ECOG score was 0 – 1 in 61% of patients. Ten percent of patients (n = 44) underwent SRT and 10% (n = 43) underwent NS. Three hundred and eighty patients had died at the time of analysis. Median OS from date of BM was 6.4 months. On univariate analysis, age &amp;lt; 60 years at BC diagnosis (8.1 vs. 4.0 months, p = 0.0007) and BM diagnosis (8.0 vs. 5.6 months, p = 0.03), ECOG status 0-1 (9.6 vs. 4.0 months, p = &amp;lt;0.0001), ER+ (8.0 vs. 6.0 months, p = 0.0007), PR+ (7.6 vs. 6.9 months, p = 0.04), HER2+ (10.5 vs. 5.6 months, p &amp;lt; 0 .0001), SRT (20.3 vs. 5.9 months, p &amp;lt; 0.0001) and NS (20.3 vs. 6.2 months, p &amp;lt; 0.0001) significantly predicted for improved OS. Triple negative status predicted for worse survival (5.6 months vs. 8.1 months, p &amp;lt; 0.0001). On multivariate analysis, ECOG status, ER+, HER2+, treatment with SRT and NS were independent predictors for OS. Conclusions: This study confirms substantial heterogeneity of prognosis in patients with BM from BC, with significantly improved survival in patients selected for SRT or surgery. Further studies are required to optimize the role of CNS radiotherapy techniques such as SRT and hippocampal sparing WBRT in patients with a favorable prognosis. Citation Format: Kothari G, De Ieso PB, Mohammed K, Ross GM. Outcomes of central nervous system radiotherapy for metastatic breast cancer: The Royal Marsden experience 2000 - 2016 [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P1-17-06.