Whole Brain Radiotherapy In Patients Research Articles

PD-L1 inhibitors combined with whole brain radiotherapy in patients with small cell lung cancer brain metastases: Real-world evidence.

Numerous studies have demonstrated that brain metastases patients may benefit from intracranial radiotherapy combined with immune checkpoint inhibitors (ICIs). However, it is unclear whether this treatment is effective for patients with small cell lung cancer brain metastases (SCLC-BMs). We conducted a retrospective study by analyzing medical records of patients with SCLC-BMs from January 1, 2017 to June 1, 2022. Data related to median overall survival (mOS), median progression-free survival (mPFS), and intracranial progression-free survival (iPFS) were analyzed. A total of 109 patients were enrolled, of which 60 received WBRT and 49 received WBRT-ICI. Compared to the WBRT alone cohort, the WBRT-ICI cohort showed longer mOS (20.4 months vs. 29.3 months, p = 0.021), mPFS (7.9 months vs. 15.1 months, p < 0.001), and iPFS (8.3 months vs. 16.5 months, p < 0.001). Furthermore, WBRT-ICI cohort had a better response rate for both BMs. (p = 0.035) and extracranial diseases (p < 0.001) compared to those receiving WBRT alone. Notably, the use of WBRT before ICI was associated with longer mOS compared to the use of WBRT after ICI (23.3 months for the ICI-WBRT group vs. 34.8 months for the WBRT-ICI group, p = 0.020). Our results indicated that WBRT combined with immunotherapy improved survival in SCLC-BMs patients compared to WBRT monotherapy. Administering WBRT prior to ICI treatment is associated with improved survival outcomes compared to WBRT following ICI treatment, for patients with SCLC-BMs. These findings highlight the significance of conducting further prospective researches on combination strategies of intracranial radiotherapy and ICI in SCLC-BMs patients.

Hippocampal sparing in whole-brain radiotherapy for brain metastases: controversy, technology and the future.

Whole-brain radiotherapy (WBRT) plays an irreplaceable role in the treatment of brain metastases (BMs), but cognitive decline after WBRT seriously affects patients' quality of life. The development of cognitive dysfunction is closely related to hippocampal injury, but standardized criteria for predicting hippocampal injury and dose limits for hippocampal protection have not yet been developed. This review systematically reviews the clinical efficacy of hippocampal avoidance - WBRT (HA-WBRT), the controversy over dose limits, common methods and characteristics of hippocampal imaging and segmentation, differences in hippocampal protection by common radiotherapy (RT) techniques, and the application of artificial intelligence (AI) and radiomic techniques for hippocampal protection. In the future, the application of new techniques and methods can improve the consistency of hippocampal dose limit determination and the prediction of the occurrence of cognitive dysfunction in WBRT patients, avoiding the occurrence of cognitive dysfunction in patients and thus benefiting more patients with BMs.

Patient reported outcomes following whole brain radiotherapy in patients with brain metastases in NSIA-LUTH Cancer Center

BackgroundBrain metastases (BM) are a common complication in advanced cancer patients, and extremely challenging to treat. Consequently, whole brain radiotherapy (WBRT) remains the standard palliative intervention for patients with BM. The present study set to evaluate the clinical benefits of WBRT by assessing the quality of life (QoL) in WBRT-treated patients with BM, in Nigeria.MethodsThis was a prospective, longitudinal, hospital-based single-centre study. Consecutive sampling methodology was used to recruit 52 patients with BM undergoing WBRT. Patients were followed up on days 7, 30, 90 and 180 after WBRT. The EORTC QLQ-C15-PAL and EORTC QLQ-BN20 were employed to report patients’ responses. The likert scale responses were linearly converted into 0 – 100 scores, and the descriptive analysis was conducted using IBM SPSS Statistics 29.0, at 95% confidence interval, using the two-tailed t-test for continuous variables or the chi-square test for categorical values. The overall survival was calculated with the Kaplan Maier method and the difference tested with Log-rank method, considering the interval from the baseline until death or end of the study.ResultsThe study cohort was predominantly females (82.7%), and accordingly, 65.4% of the respondents had a breast primary tumor. A goodness-of-fit test yielded non-significant Chi square Pearson (p = 0.325) and Deviance (p = 1.000) residuals, indicating the best fit. The median overall survival was 180 days (~ 6 months). A total of 20 patients (38%) that survived up to 180 days reported alleviated symptoms and better functioning. A significant improvement in physical functioning (p < 0.001) and emotional functioning (p = 0.031) was reported at 180 days post WBRT, compared to baseline.ConclusionsWBRT is an effective palliative intervention in patients with BM, resulting in improved QoL. More than 50% of patients that survived ~ 3 months reported alleviation of pain, and 38% of patients that survived for ~ 6 months reported a significantly improved functioning. This demonstrated the clinical benefits of WBRT in palliative care and will add to the body of data on the use of WBRT, from Africa.

MO56-2 Efficacy of whole brain radiotherapy for patients with leptomeningeal metastasis of non-small cell lung cancer: NEJ049

MO56-2 Efficacy of whole brain radiotherapy for patients with leptomeningeal metastasis of non-small cell lung cancer: NEJ049

2004P PD-L1 Inhibitors combined with whole brain radiotherapy in patients with small cell lung cancer brain metastases: Real-world evidence

2004P PD-L1 Inhibitors combined with whole brain radiotherapy in patients with small cell lung cancer brain metastases: Real-world evidence

Estimation of Conditional Neurocognitive Function Failure (NCFF) Incidence in Patients Receiving Whole Brain Radiation Therapy (WBRT) for Brain Metastases (BM): Secondary Analysis of NRG CC001

NRG CC001 was a trial that demonstrated a significantly lower risk of neurocognitive function failure (NCFF) with the use of hippocampal avoidant whole brain radiotherapy (HA-WBRT) as compared to conventional WBRT in patients with brain metastases (BM). Although a sizeable proportion of patients ultimately still did develop NCFF, the utility of this data from time of radiation treatment diminishes over time. Conditional survival analyses can provide better estimates especially for patients who demonstrate longer term neurocognitive protection. We sought to use clinical trial data to estimate the conditional risk of development of NCFF for short and longer-term survivors and to evaluate if factors prognostic of NCFF at diagnosis remained relevant over time. We performed a post hoc analysis of 518 patients enrolled in NRG CC001, a phase III trial in which patients with BM were randomly assigned to WBRT plus memantine or HA-WBRT plus memantine, using data obtained from the NCI NCTN Data Archive. In this secondary analysis, cumulative incidence function and Gray's test were used to estimate conditional NCFF incidence for the entire cohort and between arms at various time points of survivorship without neurocognitive dysfunction. Risk factors were analyzed using cause-specific multivariable Cox proportional hazards modeling analysis (MVA). Overall, the cumulative risk of development NCFF by 6 months was 64.5%. Following 2- (n = 259), 4- (n = 74), 6- (n = 43), and 8-month (n = 26) survivorship without NCFF, the conditional probability of developing neurocognitive impairment within the next 2 months were 70.1%, 27.7%, 12.7%, and 3.8%, and within the next 4 months were 78.1%, 35.4%, 15.6%, and 3.8%, respectively. For those who retained intact neurocognitive function at 2 months, only receipt of HA-WBRT (HR = 0.743, P = 0.033) and age ≤61 (HR = 0.620, P = 0.003) were predictive on MVA for decreased risk of NCFF. Prognostic factors predictive of NCFF at diagnosis were no longer associated with decreased risk of NCFF following 4 months of survivorship without cognitive impairment. Patients who achieved survivorship of ≥4 months had similar conditional risk of cognitive dysfunction between treatment arms (Gray's test, P = 0.219), and this trend persisted for patients free of NCFF at ≥6 and 8 months. Our data highlight that the greatest risk for development of NCFF after WBRT is in within the first 4 months after treatment. Conditional risk of NCFF for patients who have survived ≥4-, 6-, and 8- months without NCFF steadily decreases the longer survivorship is; this risk also appears to plateau. HA-WBRT confers reduced risk of NCFF at time of diagnosis and for short-term survivors without NCFF. Most importantly, these data can be used to counsel patients about their conditional risk of neurocognitive dysfunction over time, and suggest that those who are able to remain free of cognitive impairment may have lower risks of developing NCFF in the future.

Stereotactic radiosurgery versus whole-brain radiotherapy in patients with 4–10 brain metastases: A nonrandomized controlled trial

Background and PurposeThere is no randomized evidence comparing whole-brain radiotherapy (WBRT) and stereotactic radiosurgery (SRS) in the treatment of multiple brain metastases. This prospective nonrandomized controlled single arm trial attempts to reduce the gap until prospective randomized controlled trial results are available. Material and MethodsWe included patients with 4–10 brain metastases and ECOG performance status ≤ 2 from all histologies except small-cell lung cancer, germ cell tumors, and lymphoma. The retrospective WBRT-cohort was selected 2:1 from consecutive patients treated within 2012–2017. Propensity-score matching was performed to adjust for confounding factors such as sex, age, primary tumor histology, dsGPA score, and systemic therapy. SRS was performed using a LINAC-based single-isocenter technique employing prescription doses from 15-20Gyx1 at the 80% isodose line. The historical control consisted of equivalent WBRT dose regimens of either 3Gyx10 or 2.5Gyx14. ResultsPatients were recruited from 2017–2020, end of follow-up was July 1st, 2021. 40 patients were recruited to the SRS-cohort and 70 patients were eligible as controls in the WBRT-cohort. Median OS, and iPFS were 10.4 months (95%-CI 9.3-NA) and 7.1 months (95%-CI 3.9–14.2) for the SRS-cohort, and 6.5 months (95%-CI 4.9–10.4), and 5.9 months (95%-CI 4.1–8.8) for the WBRT-cohort, respectively. Differences were non-significant for OS (HR: 0.65; 95%-CI 0.40–1.05; P =.074) and iPFS (P =.28). No grade III toxicities were observed in the SRS-cohort. ConclusionThis trial did not meet its primary endpoint as the OS-improvement of SRS compared to WBRT was non-significant and thus superiority could not be proven. Prospective randomized trials in the era of immunotherapy and targeted therapies are warranted.

Mask dependency of the lacrimal gland dose under whole brain radiotherapy when the six-degrees of freedom couch is not available.

Dry eye syndrome has been recently reported in patients who underwent whole brain radiotherapy (WBRT). WBRT based on a couch with three-degrees of freedom (3D) can occasionally be performed in which the rotational head motion is not corrected. This study assessed the dependency of the rotational errors on the mask and the dose variation of the lens and lacrimal gland in WBRT patients. Translational and rotational setup errors were obtained at the first treatment with cone-beam CT (CBCT) for patients under WBRT and frameless stereotactic radiosurgery (SRS) (n=20 each) immobilized using a conventional WB mask and an SRS mask with a bite block, respectively. For the CT sets of SRS cases, WBRT plans were generated for the study. To simulate the rotational error, rotated CT images were created with each rotational error, on which initial WBRT plans were copied and doses were recalculated. The lens and lacrimal gland doses with and without rotation errors were compared. Despite similar translational setup errors for the two masks, the SRS mask showed a dramatic reduction in rotational errors compared to those of the WB mask. The errors varied within -2.9° to 2.9° and -1.2° to 0.7° for the WB and SRS masks, respectively. Accordingly, the SRS mask confined the change in the maximum lens dose, mean dose of the lacrimal gland, and lacrimal volume receiving 15Gy to one-third of those using the WB mask. When the six-degrees of freedom (6D) couch is not available, the frameless SRS mask is beneficial to WBRT for the faithful treatment as it was planned.

Stereotactic radiosurgery versus whole-brain radiotherapy after resection of solitary brain metastasis: A systematic review and meta-analysis

ObjectiveThe standard of care in patients with solitary brain metastasis involves surgical resection and postoperative whole-brain radiotherapy (WBRT). However, WBRT is associated with adverse effects, mainly neurocognitive deterioration. Stereotactic radiosurgery (SRS) is a more targeted form of radiation therapy that could be as effective as WBRT without the detrimental neurocognitive decline. MethodsWe performed the first systematic review and meta-analysis comparing postoperative SRS versus postoperative WBRT in patients with one resected brain metastasis. PubMed, Scopus, and Cochrane library were systematically searched for studies comparing the efficacy of the two radiation modalities in terms of local and distant brain control, leptomeningeal disease control, and overall survival. Additionally, we extracted patients’ neurocognitive function and quality of life after each postoperative radiation form. ResultsFour studies with 248 patients (128: WBRT, 120: SRS) were included in our analysis. There was no difference between SRS and WBRT in the risk of local recurrence (RR = 0.92, CI = 0.51–1.66, p = 0.78, I2 = 0%) and leptomeningeal disease (RR = 1.21, CI = 0.49–2.98, p = 0.67, I2 = 18%), neither in the patients’ overall survival (HR = 1.06, CI = 0.61–1.85, p = 0.83, I2 = 63%). Nevertheless, SRS appeared to increase the risk of distant brain failure (RR = 2.03, CI = 0.94–4.40, p = 0.07, I2 = 61%). Neurocognitive function and quality of life in the SRS group were equal or superior to the WBRT group. ConclusionsAlthough SRS may increase the risk of distant brain failure, it appears to be as effective as WBRT in terms of local control, risk of leptomeningeal disease, and overall survival while sparing the patients of the detrimental, WBRT-associated cognitive deterioration.

P03.03.A STEREOBRAIN: Stereotactic radiosurgery versus whole-brain radiotherapy in patients with 4-10 brain metastases - a non-randomized controlled trial

Abstract Background Since the JLGK0901 study described non-inferiority of stereotactic radiosurgery (SRS) of 5-10 compared to 2-4 brain metastases in 2014, it has been widely discussed if SRS should replace whole brain radiotherapy (WBRT) in 5 - 10 brain metastases though lacking randomized evidence. At our department, WBRT has been the treatment of choice in 4-10 brain metastases until 2017. This paradigm was entirely changed to include patients within the STEREOBRAIN trial (DRKS00014694). We designed this prospective controlled single arm trial to systematically introduce SRS to 4 to 10 brain metastases comparing this new treatment regimen with the former approach. We aimed at showing a survival benefit of this novel treatment paradigm. Material and Methods Inclusion criteria were 4-10 brain metastases, largest diameter 2.5 cm, all histologies except SCLC, germ cell tumors, lymphoma, and ECOG ≤ 2. The retrospective WBRT cohort was identically selected from consecutive patients from 2012 to 2017 in a 1:2 fashion. At a significance level of 5%, a total number of 99 events (deaths) across the two groups allows to detect an increase in median OS from 6 months (retrospective WBRT cohort) to 11 months (SRS) considered clinically relevant (and corresponding to a hazard ratio of 0.55 assuming exponential distributions of survival times within groups) with a power of 80%. Propensity-score matching was performed to take confounders into account given the inherent bias caused by different treatment periods. Multiple brain mets SRS was performed using a single-isocenter technique. Results Patients were recruited from 2017 - 2020 and end of F/U was July 1st 2021. Forty patients were recruited to the SRS cohort and 70 patients were eligible within the WBRT cohort (81 events altogether). Median follow-up, OS and intracranial progression free survival were 21.6 months (95%-CI 19.8-NA), 10.4 months (95%-CI 9.3-NA) and 7.1 months (95%-CI 3.9-14.2) for the SRS-cohort, and 61.4 months (95% 54.6-NA), 6.5 months (95%-CI 4.9-10.4) and 5.9 months (95%-CI 4.1-8.8) for the WBRT-cohort, respectively. The Cox-model yielded a trend for improved survival within the SRS-cohort, HR 0.65 (95%-CI 0.4-1.1); p=0.076. After optimal propensity score matching, OS was significantly superior for the SRS-cohort (HR 0.53 (95%-CI 0.32-0.86), p=0.01). No grade III toxicities were observed in the SRS-cohort. Conclusion Despite all limitations of a historical control and missing the target number of events, there was a clear signal of improved survival with SRS compared to WBRT for patients with 4-10 metastases. Whether adapted WBRT (hippocampal sparing, simultaneous integrated boost) or SRS is to be preferred needs to be investigated in the future.

Retrospective study of hypofractionated stereotactic radiotherapy combined with whole brain radiotherapy for patients with brain metastases

Background and purposeTo evaluate the clinical outcomes of hypofractionated stereotactic radiotherapy (HFSRT) combined with whole brain radiotherapy (WBRT) in patients with brain metastases (BMs).Materials and methodsFrom May 2018 to July 2020, 50 patients (111 lesions) received HFSRT (18 Gy/3F) + WBRT (40 Gy/20F). The RECIST 1.1 and RANO-BM criteria were used to evaluate treatment efficacy. Five prognostic indexes (RPA, GPA, SIR, BS-BM, and GGS) were applied. The primary endpoint was intracranial local control (iLC). Secondary endpoints were overall survival (OS) and the safety of treatment.ResultsIntracranial objective response rates (iORR) using the RECIST 1.1 and RANO-BM criteria were 62.1% and 58.6%, respectively. The iLC rate was 93.1%, the 6- and 12-month iLC rates were 90.8% and 57.4%, respectively. The median intracranial progression-free survival (iPFS) was not reached (range 0–23 months). The 6-, 12-, and 24-month OS rates were 74.2%, 58.2%, and 22.9%, respectively. The KPS score showed statistical significance in univariate analysis of survival. The 6, 12, and 24 month OS rates for patients with KPS ≥ 70 were 83.8%, 70.5%, and 29.7%, respectively. The median survival time (MST) for all patients and for patients with KPS ≥ 70 were 13.6 and 16.5 months, respectively. Sex, KPS score, and gross tumor volume were significant factors in the multivariate analysis of survival. OS was significantly associated with RPA, SIR, BS-BM, and GGS classes. No acute toxicities of grade 3 or higher were noted.ConclusionHFSRT combined with WBRT is a safe and effective local treatment modality for BM patients.

Efficacy and safety of recombinant human endostatin combined with whole-brain radiation therapy in patients with brain metastases from non-small cell lung cancer

Background and purposeBrain metastasis (BM) is the leading cause of poor prognosis in non-small cell lung cancer (NSCLC) patients. To date, whole-brain radiation therapy (WBRT) is a standard treatment for patients with multiple BMs, while its effectiveness is currently unsatisfactory. This study aimed to investigate the effects of Rh-endostatin combined with WBRT on NSCLC patients with BMs. Materials and MethodsA total of 43 patients with BM were randomly divided into two groups. The Rh-endostatin combination group (n = 19) received Rh-endostatin combined with WBRT, and the radiation group (n = 24) received WBRT only. The primary endpoint of the study was progression-free survival (PFS), and the secondary endpoints were intracranial progressionfree survival (iPFS), overall survival (OS), objective response rate (ORR), and changes in the cerebral blood volume (CBV) and cerebral blood flow (CBF). ResultsMedian PFS (mPFS) was 8.1 months in the Rh-endostatin combination group and 4.9 months in the radiation group (95%CI 0.2612–0.9583, p = 0.0428). Besides, the median iPFS was 11.6 months in the Rh-endostatin combination group and 4.8 months in the radiation group (95%CI 0.2530–0.9504, p = 0.0437). OS was 14.2 months in the Rh-endostatin combination group and 6.4 months in the radiation group (95%CI 0.2508–1.026, p = 0.0688). CBV and CBF in the Rh-endostatin combination group were better improved than that in the radiation group, which indicated that Rh-endostatin might improve local blood supply and microcirculation. ConclusionRh-endostatin showed better survival and improved cerebral perfusion parameters, which may provide further insights into the application of Rh-endostatin for NSCLC patients with BMs.

Stereotactic radiosurgery versus whole brain radiotherapy in patients with intracranial metastatic disease and small-cell lung cancer: a systematic review and meta-analysis.

Patients with small-cell lung cancer (SCLC) are at high risk for intracranial metastatic disease (IMD). Although stereotactic radiosurgery (SRS) has supplanted whole brain radiotherapy (WBRT) as first-line treatment for IMD in most solid cancers, WBRT remains first-line treatment for IMD in patients with SCLC. We aimed to evaluate the efficacy of SRS in comparison with WBRT and assess treatment outcomes following SRS. In this systematic review and meta-analysis, we searched MEDLINE, Embase, CENTRAL, and grey literature sources for controlled trials and cohort studies published in English reporting on SRS for IMD treatment in patients with SCLC from inception to March 23, 2022. Studies were excluded that did not report on SRS for IMD secondary to SCLC. Summary data were extracted. The primary outcome was overall survival, presented as pooled hazard ratios (HR) through random-effects meta-analysis for studies comparing SRS with WBRT with or without SRS boost, and as medians for single-arm SRS studies. This study is registered with the Open Science Framework, DOI 10.17605/OSF.IO/8M4HC, and PROSPERO, CRD42021258197. Of 3823 identified records, 31 were eligible for inclusion; seven were included in the meta-analysis. Overall survival following SRS was longer than following WBRT with or without SRS boost (HR 0·85; 95% CI 0·75-0·97; n=7 studies; n=18 130 patients), or WBRT alone (0·77; 0·72-0·83; n=7 studies; n=16 961 patients), but not WBRT plus SRS boost (1·17, 0·78-1·75; n=4 studies; n=1167 patients). Using single-arm studies, pooled median overall survival from SRS was 8·99 months (95% CI 7·86-10·16; n=14 studies; n=1682 patients). Between-study heterogeneity was considerable when pooled among all comparative studies (I2=71·9%). These results suggest survival outcomes are equitable following treatment with SRS compared with WBRT in patients with SCLC and IMD. Future prospective studies should focus on tumour burden and differences in local and distant intracranial progression between WBRT-treated and SRS-treated patients with SCLC. None.

Stereotactic radiosurgery (SRS) versus whole brain radiation therapy (WBRT) in patients with small cell lung cancer (SCLC) and intracranial metastatic disease (IMD): A systematic review and meta-analysis.

8570 Background: Patients with SCLC are at high risk for the development of IMD and, subsequently, rapid intracranial progression. SRS has supplanted WBRT as first-line treatment for IMD in most solid cancers, but WBRT remains first-line treatment for IMD in SCLC patients. Data on SRS in SCLC are limited to small retrospective studies. Methods: Studies reporting on SRS in SCLC patients with IMD were collected from EMBASE, MEDLINE, CENTRAL, and grey literature sources (n = 3,732 studies). Random-effects meta-analysis pooled hazard ratios (HR) for overall survival (OS) between SRS and WBRT ± SRS boost, as well as medians for OS in months (mo) and risk rates for intracranial local (LC) and intracranial distant control (DC) in single-arm SRS studies. Results: OS following SRS was non-inferior compared with WBRT ± SRS boost (HR 0.90; 95% confidence interval (95CI), 0.73-1.10; n = 7 studies; n = 18,130 patients), and superior compared with WBRT alone (HR 0.80; 95CI, 0.66-0.96; n = 7 studies; n = 16,961 patients). Pooled median OS from single-arm studies following SRS was 8.99 mo (95CI, 7.86-10.15; n = 14 studies; n = 1,682 patients). Pooled LC and DC estimates following SRS were 81% (95CI, 67%-99%) and 66% (95CI, 50%- 86%), respectively, at 6 mo, and 78% (95CI, 61%-98%) and 58% (95CI, 46%-75%), respectively, at 12 mo. Conclusions: This systematic review and meta-analysis provides evidence that SRS may achieve analogous survival outcomes compared with WBRT in patients with SCLC and IMD, indicating that a subset of SCLC patients may benefit from first-line SRS treatment. Prospective trials should investigate the impact of metastatic burden as well as LC and DC differences between WBRT- and SRS-treated SCLC patients.

Efficacy and safety of recombinant human endostatin combined with whole-brain radiotherapy in patients with brain metastases from NSCLC.

e21158 Background: Brain metastasis (BM) is the first cause of poor prognosis in non-small cell lung cancer (NSCLC) patients. To date, localized whole-brain radiotherapy (WBRT) is still the therapeutic option for patients with extensive BM. However, effectiveness is currently unsatisfactory. This study aimed to investigate the effects of Rh-endostatin combined with WBRT on NSCLC patients with BMs. Methods: 43 NSCLC patients with BMs were divided into two groups randomly. Rh-endostatin combination group (n = 19) received WBRT combined with Rh-endostatin, and radiation group (n = 24) received WBRT alone. The primary endpoint of the study was progression free survival (PFS). The secondary endpoints were intracranial progression free survival (iPFS), overall survival (OS), objective response rate (ORR) and the change of cerebral blood volume (CBV), cerebral blood flow (CBF) of the contrast medium pre- and one month post-radiation. Results: Median progression-free survival (PFS) was 8.1 months in the Rh-endostatin combination group versus 4.9 months in the radiation group (95%CI: 0.2612-0.9583, p= 0·0428). Besides, median iPFS was 11.6 months in Rh-endostatin combination group versus 4.8 months in the radiation group (95%CI：0.2530-0.9504, p= 0·0437). Overall survival (OS) was 14.2 months in the Rh-endostatin combination group versus 6.4 months in the radiation group (95%CI：0.2508-1.026, p= 0·0688). Compared with radiotherapy alone, CBV and CBF in the Rh-endostatin combination group increased more significantly than before radiotherapy, indicating that Rh-endostatin may improve local blood supply and microcirculation. Conclusions: Rh-endostatin showed better survival and a safety profile, improved cerebral perfusion and increased the quality of life of NSCLC patients with BMs. Clinical trial information: NCT03614065.

Long-term neurocognitive function after whole-brain radiotherapy in patients with melanoma brain metastases in the era of immunotherapy

BackgroundWhole-brain radiotherapy (WBRT) used to be standard of care for patients suffering from melanoma brain metastases (MBM) and may still be applicable in selected cases. Deterioration of neurocognitive function (NCF) is commonly seen during and after WBRT. Knowledge on long-term effects in melanoma patients is limited due to short survival rates. With the introduction of immune checkpoint inhibitors, patients may experience ongoing disease control, emphasizing the need for paying more attention to potential long-term adverse effects.MethodsIn this single-center study, we identified in a period of 11 years all long-term survivors of MBM who received WBRT at least 1 year prior to inclusion. NCF was assessed by Neuropsychological Assessment Battery (NAB) screening and detailed neurological exam; confounders were documented.ResultsEight patients (median age 55 years) could be identified with a median follow-up of 5.4 years after WBRT. Six patients reported no subjective neurological impairment. NAB screening revealed an average-range score in 5/8 patients. In 3/8 patients a NAB score below average was obtained, correlating with subjective memory deficits in 2 patients. In these patients, limited performance shown in modalities like memory function, attention, and spatial abilities may be considerably attributed to metastasis localization itself. Six out of 8 patients were able to return to their previous work.ConclusionFive of 8 long-term survivors with MBM after WBRT experienced little to no restriction in everyday activities. In 3 out of 8 patients, cognitive decline was primarily explained by localization of the metastases in functionally relevant areas of the brain. The results of our small patient cohort do not support general avoidance of WBRT for treatment of brain metastases. However, long-term studies including pretreatment NCF tests are needed to fully analyze the long-term neurocognitive effects of WBRT

Brain metastasis: Recent treatment modalities and future-perspectives.

With the advent of novel systemic therapies, such as molecular targeted therapy and immune checkpoint inhibitors, the treatment of advanced-stage cancer is markedly transitioning. The treatment for brain metastasis is influenced by these new therapies. Moreover, the frequency of brain metastasis is associated with cancer genetics. Since conventional cytotoxic chemotherapeutic drugs cannot easily cross the brain-blood barrier, radiotherapy plays a major role in the management of brain metastasis. Whole-brain radiotherapy (WBRT) has been frequently used, especially for multiple metastatic brain tumors; however, late adverse effects on cognitive function are a significant clinical problem of WBRT in patients with an otherwise good prognosis and overall survival rate. Some novel systemic agents are effective against brain metastasis. Moreover, advances in radiotherapy technology have made it possible to deliver optimal radiation doses to patients with brain metastasis, with fewer adverse events. Brain metastasis has a significant impact on the quality of life of patients with advanced-stage cancer; therefore, its appropriate management is an important factor in the comprehensive treatment of cancer.

Whole brain radiotherapy combined with intrathecal liposomal cytarabine for leptomeningeal metastasis\u2014a\xa0safety analysis and validation of the EANO-ESMO classification

BackgroundAlthough there is no proven standard therapy for leptomeningeal metastases (LM), treatment often includes intrathecal chemotherapy combined with whole brain radiation therapy (WBRT). Little is known about the toxicity of such combination therapies. We performed a retrospective safety analysis for the combination of intrathecal liposomal cytarabine with WBRT in patients with LM and validated the EANO-ESMO (European Association of Neuro-oncology—European Society for Medical Oncology) classification in this unique cohort.MethodsTreatment toxicities in patients diagnosed with LM between 2004 and 2014 were retrospectively analyzed according to RTOG (Radiation Therapy Oncology Group) toxicity criteria and NCI CTCAE V5.0 (National Cancer Institute Common Terminology Criteria for Adverse Events, Version 5.0). Diagnostic criteria and treatment response as assessed by EANO-ESMO classification were correlated with survival by Kaplan–Meier analysis and Breslow test.ResultsIn all, 40 patients with LM who were treated with combined WBRT and intrathecal cytarabine, were identified. Ten patients (25%) experienced adverse events ≥grade 3 according to RTOG toxicity criteria; in 22 patients (55%) NCI CTCAE ≥grade 3 were detected. Median overall survival was 124 days. Median time to neurological progression was 52 days. Patients with positive cerebrospinal fluid (CSF) cytology (n = 26) showed worse prognosis compared to patients with negative CSF cytology (n = 14; mOS (median overall survival) 84 days versus 198 days, p = 0.006, respectively). The EANO-ESMO response assessment was significantly associated with survival: “stable” (n = 7) mOS 233 days, “response” (n = 10) mOS 206 days, “progression” (n = 17) mOS 45 days, “suspicion of progression” (n = 6) mOS 133 days; overall, p < 0.001.ConclusionsIn this retrospective analysis, combined treatment of WBRT and intrathecal liposomal cytarabine shows an acceptable safety profile and may indicate a trend towards improved efficacy. The EANO-ESMO classification for diagnosis and treatment response predicts survival.

Improving on whole-brain radiotherapy in patients with large brain metastases: A planning study to support the AROMA clinical trial

PurposeTo develop a novel dose-escalated volumetric modulated arc therapy (VMAT) strategy for patients with single or multiple large brain metastases which can deliver a higher dose to individual lesions for better local control (LC), and to compare dosimetry between whole brain radiotherapy (WBRT), hippocampal-sparing whole brain radiotherapy (HS-WBRT) and different VMAT-based focal radiotherapy approaches. Methods and materialsWe identified 20 patients with one to ten brain metastases and at least one lesion larger than 15 cm3 who had received WBRT as part of routine care. For each patient, we designed and evaluated five radiotherapy treatment plans, including WBRT, HS-WBRT and three VMAT dosing models. A dose of 20 Gy in 5 fractions was prescribed to the whole brain or target volumes depending on the plan, with higher doses to smaller lesions and dose-escalated inner planning target volumes (DE-iPTV) in VMAT plans, respectively. Treatment plans were evaluated using the efficiency index, mean dose and D0.1 cc to the target volumes and organs at risk. ResultsCompared with WBRT, VMAT plans achieved a significantly more efficient dose distribution in brain lesions, especially with our DE-iPTV model, while minimising the dose to the normal brain and other organs at risks (OARs) (p < 0.05). ConclusionsVMAT plans obtained higher doses to brain metastases and minimised doses to OARs. Dose-escalated VMAT for larger lesions allows higher radiotherapy doses to be delivered to larger lesions while maintaining safe doses to OARs.

NQPC-5 Does high-dose methotrexate-based chemotherapy for relapsed primary CNS lymphoma increase a risk of leukoencephalopathy with prior whole brain radiotherapy?

Backgrounds: Standard care for primary central nervous system lymphoma (PCNSL) comprises high-dose (HD) methotrexate (MTX) -based chemotherapy with or without consolidation whole brain radiotherapy (WBRT). HD-MTX administration following WBRT has been suggested to increase a risk of leukoencephalopathy. However, given that there are no other agents with efficacy similar to or better than MTX, patients with relapsed PCNSL may often be treated with regimens containing HD-MTX if the initial MTX treatment achieved a long-term complete remission. Here, we retrospectively analyzed prevalence and an extent of white mater damages in association with prior WBRT in patients with relapsed PCNSL treated with HD-MTX based therapy. Patients & methods: Among 79 patients with relapsed/refractory PCNSL in a total of 162 patients with newly-diagnosed PCNSL treated in our institution from April, 2000 to February, 2021, 35 patients were identified with evaluable KPS, MMSE, and Fazekas scale data at both baseline and follow-up periods. Of the 35 patients, 22 were treated with chemotherapy at a relapse (10 with prior WBRT, while 12 without WBRT), and were included in this preliminary study. Results: In the WBRT group (male/female: 5/5), median age was 65 years (range, 45–73), initial median KPS was 70 (40–90), and median WBRT dose was 27 Gy (23.4–40). Median progression-free survival (mPFS) was 11.8 months, and median overall survival (mOS) was not reached. In the non-WBRT group (M/F 8/4), median age 75 (62–84), initial mKPS 80 (50–90), mPFS 16.2 m, and mOS not reached. Initial KPS and MMSE score tended to be worse in WBRT group, presumably due to enrichment of patients with poorer performance status and more comorbidities. A decline in the Fazekas score was not associated with MMSE deterioration.Conclusions: The preliminary analysis was not informative enough, and further extensive imaging analysis will be exploited.