Radiotherapy For Brain Metastases Research Articles

Management of Gestational Trophoblast Disease: An Integrative Review of National and International Guidelines

GTD (Gestational Trophoblastic Disease) is a pathology that encompasses benign and malignant clinical forms, affects women of childbearing age, has a variable incidence and is more frequent in developing or underdeveloped countries, colliding with the economic barrier. The frequent absence of clear protocols and guidelines for the correct diagnosis and treatment of the aforementioned pathology results in inadequate risk classification, imprecise treatment and failed post-therapeutic observation, increasing the risk of relapses, morbidity and mortality. The present study aims to compare the different national and international guidelines in the management of GTD, through an integrative review. Nine articles were selected and it was observed that the main international reference centers are agreed with the management suggested by the IFGO (International Federation of Gynecology and Obstetrics), being the conduct in the Hydatidiform Mole (HM): evacuation by suction and curettage under ultrasound guidance, followed by hCG monitoring every 1 - 2 weeks until normalized; in low-risk GTN (Gestational Trophoblastic Neoplasm): chemotherapy with methotrexate or actinomycin D, in high-risk: EMA/CO protocol, in ultra-high-risk EMA/PE, methotrexate with radiotherapy for brain metastases. All medical societies recommend the registration of these patients in GTD screening centers, endorse the use of the IFGO scoring system (2000) and recommend the surgical management of placental site trophoblastic or epithelioid tumors, as chemotherapy is less effective in these cases. The controversies are in the proper follow-up after the treatment of HM, use of ultrasound to evacuate the uterus, administration of anti-D immunoglobulin, time of oxytocin infusion and rescue regimens that can be used in cases of resistant or recurrent GTN. Establishing and complying with consistent guidelines can improve patient care, with early diagnosis of the pathology and its complications, reducing the rate of recurrence, morbidity and mortality, especially in less developed countries.

Treatment of breast cancer brain metastases: radiotherapy and emerging preclinical approaches.

The breast is one of the common primary sites of brain metastases (BM). Radiotherapy for BM from breast cancer may include whole brain radiation therapy (WBRT), stereotactic radiosurgery (SRS), and stereotactic radiotherapy (SRT), but a consensus is difficult to reach because of the wide and varied protocols, indications, and outcomes of these interventions. Overall, dissemination of disease, patient functional status, and tumor size are all important factors in the decision of treatment with WBRT or SRS. Thus far, previous studies indicate that WBRT can improve tumor control compared to SRS, but increase side effects, however no randomized trials have compared the efficacy of these therapies in BM from breast cancer. Therapies targeting long non-coding RNAs and transcription factors, such as MALAT1, HOTAIR, lnc-BM, TGL1, and ATF3, have the potential to both prevent metastatic spread and treat BM with improved radiosensitivity. Given the propensity for HER2+ breast cancer to develop BM, the above-mentioned cell lines may represent an important target for future investigations, and the development of everolimus and pyrotinib are equally important.

Eight Months' Recurrence-free Survival after Tumorectomy and Fractionated Stereotactic Radiotherapy for Brain Metastasis of a Pancreatic Tumor

Eight Months' Recurrence-free Survival after Tumorectomy and Fractionated Stereotactic Radiotherapy for Brain Metastasis of a Pancreatic Tumor

Association of Pretreatment Hippocampal Volume With Neurocognitive Function in Patients Treated With Hippocampal Avoidance Whole Brain Radiation Therapy for Brain Metastases: Secondary Analysis of NRG Oncology/RTOG 0933

PurposeHippocampal volume (HV) is an established predicting factor for neurocognitive function (NCF) in neurodegenerative disease. Whether the same phenomenon exists with hippocampal-avoidant whole brain radiation therapy is not known; therefore, we assessed the association of baseline HV with NCF among patients enrolled on RTOG 0933. Methods and MaterialsHippocampal volume and total brain volume were calculated from the radiation therapy plan. Hippocampal volume was correlated with baseline and 4-month NCF scores (Hopkins Verbal Learning Test–Revised [HVLT-R] Total Recall [TR], Immediate Recognition, and Delayed Recall [DR]) using Pearson correlation. Deterioration in NCF was defined per the primary endpoint of RTOG 0933(mean 4-month relative decline in HVLT-R DR). Comparisons between patients with deteriorated and nondeteriorated NCF were made using the Wilcoxon test. ResultsForty-two patients were evaluable. The median age was 56.5 years (range, 28-83 years), and 81% had a class II recursive partitioning analysis. The median total, right, and left HVs were 5.4 cm3 (range, 1.9-7.4 cm3), 2.8 cm3 (range, 0.9-4.0 cm3), and 2.7 cm3 (range, 1.0-3.7 cm3), respectively. The median total brain volume was 1343 cm3 (range, 1120.5-1738.8 cm3). For all measures of corrected HV, increasing HV was associated with higher baseline HVLT-R TR and DR scores (ρ: range, 0.35-0.40; P-value range, .009-.024) and 4-month TR and DR scores (ρ: range, 0.29-0.40; P-value range, .009-.04), with the exception of right HV and 4-month DR scores (ρ: 0.29; P = .059). There was no significant association between HV and NCF change between baseline and 4 months. Fourteen patients (33.3%) developed NCF deterioration per the primary endpoint of RTOG 0933. There was no significant difference in HV between patients with deteriorated and nondeteriorated NCF, although in all instances, patients with deteriorated NCF had numerically lower HV. ConclusionsLarger HV was positively associated with improved performance on baseline and 4-month HVLT-R TR and DR scores in patients with brain metastases undergoing hippocampal-avoidant whole brain radiation therapy but was not associated with a change in NCF.

The Study of Cerebral Blood Flow Variations during Brain Metastases Radiotherapy

Purpose: The aim of this study was to investigate the cerebral blood flow (CBF) variations during brain metastases (BMs) radiotherapy (RT) applying with magnetic resonance (MR) 3D-arterial spin labeling (ASL). Materials and Methods: A total of 26 BM patients with 54 tumors were retrospectively enrolled. MR examinations were performed before and during RT (30–50 Gy) with a total dose of 36–60 Gy (12–30 fractions) including contrast-enhanced T1-weighted, T2 Flair, and 3D-ASL images. The relationship between CBF changes and the largest cross-sectional area changes in BMs was investigated. And CBF changes in BMs, normal brain tissue, and peritumoral edema areas were analyzed under different dose gradients that were divided into 10 Gy intervals. Results: The largest cross-sectional areas and CBF of 54 BMs decreased by 26.46% and 29.64%, respectively, during RT (p < 0.05), but there was no correlation between the 2 changes (p > 0.05). The rates of CBF decrease in BMs were 33.75%, 24.61%, and 27.55% at 30–40, 40–50, and >50 Gy, respectively (p < 0.05). In normal brain tissue with dose gradients of 0–10, 10–20, 20–30, 30–40, 40–50, and >50 Gy, the CBF decreased by 7.65%, 11.12%, 18.42%, 20.23%, 19.79%, and 17.89%, respectively (p < 0.05). The CBF decreases reached a maximum at 30–40 Gy in normal brain tissue as well as BMs. In contrast, the CBF decreases of peritumoral edema areas increased as the dose gradients increased. Moreover, the CBF changes of BMs were more notable than those in normal brain tissue and peritumoral edema areas. Conclusion: CBF changes can be feasibly assessed in different brain regions during RT based on 3D-ASL. The changes should be considered as a critical factor to determine the personal radiation dose for BMs, normal brain tissue, and peritumoral edema areas.

MET-5 Salvage surgical resection after linac-based stereotactic radiosurgery and radiotherapy for brain metastasis

Methods: Between November 2009 and December 2018, 335 consecutive patients with 1085 brain metastases were treated with SRS/fSRT for newly diagnosed brain metastasis at our hospital. Nineteen of 335 patients (5.6%) and 19 of 1044 brain metastases (1.8%) went on to receive SSR after SRS/fSRT during this study period. Two patients underwent multiple surgical resections. Nineteen consecutive patients underwent 21 SSRs. Results: The median time from initial SRS/fSRT to SSR was 14 months (range: 2–96 months). The median follow-up after SSR was 15 months (range: 2–76 months). The range of tumor volume at initial SRS/fSRT was 0.12–21.46 cm3 (median: 2.19 cm3). Histopathological diagnosis after SSR was recurrence, radiation necrosis (RN) and cyst formation in 13 and 6 cases, respectively. The time from SRS/fSRT to SSR were shorter in the recurrence than in the RNs and cyst formation, but these differences did not reach statistical significance (p = 0.07). The median survival time from SSR and from initial SRS/fSRT was 17 months and 74 months, respectively. The cases with recurrence had a significantly shorter survival time from initial SRS/fSRT than those without recurrence (p=0.045).Conclusion: The patients treated with SRS/fSRT for brain metastasis need long-term follow-up. SSR is a safe and effective treatment for the recurrence, RN, and cyst formation after SRS/fSRT for brain metastasis.

Stereotactic radiosurgery for brain metastases from pelvic gynecological malignancies: oncologic outcomes, validation of prognostic scores, and dosimetric evaluation

IntroductionStereotactic radiosurgery is a well-established treatment option in the management of brain metastases. Multiple prognostic scores for prediction of survival following radiotherapy exist, but are not disease-specific or validated for...

Advances in radiotherapy for brain metastases.

As novel systemic therapies yield improved survival in metastatic cancer patients, the frequency of brain metastases continues to increase. Over the years, management strategies have continued to evolve. Historically, stereotactic radiosurgery has been used as a boost to whole-brain radiotherapy (WBRT) but is increasingly being used as a replacement for WBRT. Given its capacity to treat both macro- and micro-metastases in the brain, WBRT has been an important management strategy for years, and recent research has identified technologic and pharmacologic approaches to delivering WBRT more safely. In this review, we outline the current landscape of radiotherapeutic treatment options and discuss approaches to integrating radiotherapy advances in the contemporary management of brain metastases.

DDRE-02. PATIENTS WITH LEPTOMENINGEAL METASTASES FROM NSCLC BENEFITED FROM INTRATHECAL PEMETREXED AFTER FAILURE TO TYROSINE KINASE INHIBITORS: TWO CASE REPORTS

Abstract BACKGROUND The incidence of leptomeningeal metastasis (LM) is 3%-5% in NSCLC patients; the incidence is even higher in patients with EGFR mutations or ALK gene rearrangement. The prognosis of NSCLC patients with LM is poor with an overall survival (OS) of 3 months with contemporary treatment. METHODS Here we report two cases of patients with leptomeningeal metastases from NSCLC who benefited from intrathecal pemetrexed after failure to tyrosine kinase inhibitors(TKIs). RESULTS A 53-year-old woman, diagnosed with adenocarcinoma of the lung with ALK rearrangement, suffered form right limb weakness, dysphagia after multi-line targeted therapy and radiotherapy for brain metastases. Evaluation revealed a rapidly progressing right brainstem mass and diffuse leptomeningeal enhanced. And cytological examination of CSF showed neoplastic cells, which definitely diagnosed as LM. After first intrathecal injection of 30mg pemetrexed every three weeks, the patient's symptoms improved. There were no significant treatment side effects and the quality of life was not affected during the five subsequent treatments. Another patient was a 32-year-old man, diagnosed with adenocarcinoma of the lung with EGFR E24-RAD51E4 fusion mutation with KPS score 30. LM was confirmed after multiline therapy. He suffered form blurred vision and drooping eyelid. Similarly, after first intrathecal injection of 20mg pemetrexed every week, the patient's symptoms improved and KPS score increased gradually. And level II leukopenia was detected during subsequent treatments. Combined with intrathecal pemetrexed progression-free survival (PFS) were 3 months in two NSCLC patients with LM harboring ALK/EGFR mutation . And the quality of life of patients were effectively increased. CONCLUSION Combination therapy third generation EGFR/ALK agents with intrathecal chemotherapy might be benefited in overall survival.

The Tumor Control According to Radiation Dose of Gamma Knife Radiosurgery for Small and Medium-Sized Brain Metastases from Non-Small Cell Lung Cancer.

ObjectiveThe effectiveness of gamma knife radiosurgery (GKR) in the treatment of brain metastases is well established. The aim of this study was to evaluate the efficacy and safety of maximizing the radiation dose in GKR and the factors influencing tumor control in cases of small and medium-sized brain metastases from non-small cell lung cancer (NSCLC). MethodsWe analyzed 230 metastatic brain tumors less than 5 mL in volume in 146 patients with NSCLC who underwent GKR. The patients had no previous radiation therapy for brain metastases. The pathologies of the tumors were adenocarcinoma (n=207), squamous cell carcinoma (n=18), and others (n=5). The radiation doses were classified as 18, 20, 22, and 24 Gy, and based on the tumor volume, the tumors were categorized as follows : small-sized (less than 1 mL) and medium-sized (1–3 and 3–5 mL). The progression-free survival (PFS) of the individual 230 tumors and 146 brain metastases was evaluated after GKR depending on the pathology, Eastern Cooperative Oncology Group (ECOG) performance score (PS), tumor volume, radiation dose, and anti-cancer regimens. The radiotoxicity after GKR was also evaluated. ResultsAfter GKR, the restricted mean PFS of individual 230 tumors at 24 months was 15.6 months (14.0–17.1). In small-sized tumors, as the dose of radiation increased, the tumor control rates tended to increase (p=0.072). In medium-sized tumors, there was no statistically difference in PFS with an increase of radiation dose (p=0.783). On univariate analyses, a statistically significant increase in PFS was associated with adenocarcinomas (p=0.001), tumors with ECOG PS 0 (p=0.005), small-sized tumors (p=0.003), radiation dose of 24 Gy (p=0.014), synchronous lesions (p=0.002), and targeted therapy (p=0.004). On multivariate analyses, an improved PFS was seen with targeted therapy (hazard ratio, 0.356; 95% confidence interval, 0.150–0.842; p=0.019). After GKR, the restricted mean PFS of brain at 24 months was 9.8 months (8.5–11.1) in 146 patients, and the pattern of recurrence was mostly distant within the brain (66.4%). The small and medium-sized tumors treated with GKR showed radiotoxicitiy in five out of 230 tumors (2.2%), which were controlled with medical treatment. ConclusionThe small-sized tumors were effectively controlled without symptomatic radiation necrosis as the radiation dose was increased up to 24 Gy. The medium-sized tumors showed potential for symptomatic radiation necrosis without signifcant tumor control rate, when greater than 18 Gy. GKR combined targeted therapy improved the tumor control of GKR-treated tumors.

Heightened Sensitivity of Germline BRCA Mutant Patients Treated With Concurrent or Adjuvant PARP Inhibition and Radiotherapy for Brain Metastases

Limited data exist regarding the effect of radiotherapy (RT) and poly (ADP-ribose) polymerase inhibition (PARPi) for brain metastases (BM). However, RT is known to elevate PARP levels and thus, PARPi may have radiosensitizing effects. We hypothesize that among BRCA germline mutant (BRCAgm) patients, receipt of adjuvant and/or concurrent PARPi and RT for BM delays time to intracranial failure.With IRB approval, we reviewed BRCAgm patients and BM who received oral PARPi and RT-whole brain (WBRT, 30 Gy/10 fractions) or stereotactic radiosurgery (SRS, 21-27 Gy/1-3 fractions)-between 2010-2020. Of 33 patients identified, 12 were excluded for any progression on PARPi, requiring salvage RT; and 6 were excluded for > 2 month interval between RT and adjuvant PARPi. We stratified into groups based on timing of PARPi relative to RT: 1) Patients on PARPi prior to RT and maintained on PARPi thereafter ("Concurrent"); and 2) Patients who initiated PARPi after completion of RT ("Adjuvant"). Primary outcomes were intracranial progression-free survival (PFS) and overall survival (OS) with estimates generated using the Kaplan-Meier method. Secondary outcome was toxicity. BrainGPA was used to predict median survival in patients with eligible histologies.Fifteen patients (female, N = 12; male, N = 3) met inclusion criteria. Median (range) KPS was 80 (70-90), and age at radiation was 50 years (32-76). Median follow-up was 10.9 months (3.1-27.8). Sixty-three percent had breast cancer (N = 10) and 87% received Olaparib (N = 13). Among 8 concurrent patients, 5 received SRS and 3 received WBRT; median intracranial PFS was 5.7 months (1.9-17.5) and median OS was 10.4 months (3.1-17.5). Among 7 adjuvant patients, 4 received SRS and 3 WBRT; median intracranial PFS was 9.9 months (4.0-18.2) and median OS was 10.9 months (4.0-28.4). Median time to PARPi after RT was 2 weeks. Of 10 patients with histologies eligible for BrainGPA calculation, 90% exceeded the predicted median survival. There were no cases of grade ≥3 toxicity, including radionecrosis.In this small series of BRCAgm patients, RT with concurrent and/or adjuvant PARPi for BM was feasible and safe. Several patients had long intervals of intracranial PFS suggestive of heightened sensitivity to RT particularly with adjuvant PARPi. Future prospective studies in larger cohorts are warranted to determine the optimal timing of PARPi relative to brain RT.

Optimal Scheme in Hypofractionated Stereotactic Radiation Therapy for Brain Metastases

Stereotactic radiosurgery (SRS) is common technique used in the treatment of brain metastases. In lieu of single-fraction SRS, hypofractionated stereotactic radiation therapy (HF-SRT) is employed for large metastases and/or for those in sensitive areas of the brain in order minimize toxicity while maintaining effectual local control (LC) rates. There is currently no consensus on an optimal dose-fractionation, with most of the surrounding evidence being in the form of retrospective institutional studies resulting in a variety of utilized fractionation schemes. Some of these studies have suggested that BED10 may predict for improved LC. Our hypothesis is that HF-SRT delivered to BED10 ≥50 Gy would confer improved LC without a significant detriment in radionecrosis (RN) rates.A search of medical literature in PubMed/MEDLINE, Embase, and Cochrane databases was conducted using Preferred Reporting Items for Systematic Reviews and Meta-Analyses of Observational Studies in Epidemiology (PRISMA) guidelines. Search terms included 'brain metastases and 'radiosurgery' yielding studies which were individually reviewed for inclusion. To meet inclusion, studies must have 1) utilized hypofractionated stereotactic radiosurgery techniques defined as ≥2.5 Gy per fraction in the treatment of brain metastases, 2) described LC and RN rate data, and 3) administered radiosurgery as definitive or post-operative treatment. Linear regression of the logarithmically transformed 1-year LC rate weighted by the number of lesions in each study was performed. In addition, a non-parametric, exact Mann-Whitney U-test was used to test a potential difference in 1-year LC or RN rate according to whether studies achieved a median BED10 ≥50 Gy.A total of 27 studies spanning 2000 to 2019 comprising of 2399 lesions met our inclusion criteria and were analyzed. Median BED10 across all studies was 51.3 Gy (range 37.5 to 69.3), with 836 lesions receiving BED10 < 50 Gy and 1563 lesions BED10 ≥50 Gy. Median total dose and number of treatments were 30 Gy (range 23.1 to 40) and 5 fractions (range 3 to 10), respectively. There was no statistically significant difference in LC with BED10 ≥50 Gy versus BED10 < 50 Gy (2-tailed, P = 0.104), nor was there a difference in reported necrosis rate (P = 0.85). On multivariate analysis of 1-year LC, the only significant factor was volume of tumor treated, where increased tumor volume was associated with increased LC (P = 0.0011).This analysis showed there was no statistically significant difference between dose-fractionation regimens delivering BED10 ≥50 Gy versus BED10 < 50 Gy with regards to 1-year LC and the incidence of RN. Studies appeared heterogeneous and this may explain the unexpected association between increasing tumor volume and LC. Future randomized controlled trials should be conducted to identify the optimal dose-fractionation for patients with large brain metastases.O.M. Siddiqui: None. C. Haskins: None. S.M. Bentzen: Travel Expenses; University of Copenhagen. M.V. Mishra: Employee; Orthofix. Research Grant; ASTRO, Keep Punching. Advisory Board; Patient Centers Outcomes Research Institute (PCORI. Travel Expenses; Patient Centers Outcomes Research Institute (PCORI.

Cost-Effectiveness of Prophylactic Cranial Irradiation vs. MRI Surveillance for Extensive Stage Small Cell Lung Cancer

Due to conflicting prospective data, controversy exists regarding prophylactic cranial irradiation (PCI) in extensive stage small cell lung cancer (ES-SCLC). We sought to evaluate the cost-effectiveness of PCI versus MRI surveillance alone in the context of modern radiotherapy treatment modalities using available evidence and the CMS alternative payment model (APM).A Markov state transition model was constructed using software to perform a cost-effectiveness analysis comparing MRI surveillance alone with PCI for ES-SCLC. PCI in the base case analysis was assumed to be 25 Gy in 10 fractions delivered with a 3D conformal radiotherapy technique (3D-CRT) without daily image guidance. In the MRI surveillance alone arm, MRI surveillance was assumed to be performed at baseline then every 3 months for the first year and every 6 months for year 2, consistent with the surveillance plan currently being implemented in the SWOG MAVERICK cooperative group trial (NCT04155034). Clinical parameters were obtained from clinical trial data, and cost data were based on 2019 Medicare reimbursement. Strategies were compared using the incremental cost-effectiveness ratio (ICER) with effectiveness in quality-adjusted life years (QALYs) and evaluated with a willingness to pay threshold of $100,000 per QALY gained. One-way and probabilistic sensitivity analyses were performed to consider model uncertainty.In the base case scenario, PCI was not cost-effective with an ICER of $168,456 per QALY gained compared to MRI surveillance alone, assuming that overall survival was 10 months and 12.5 months for MRI surveillance alone and PCI, respectively. One-way sensitivity analysis showed that results were most sensitive to the variation of overall survival and cognitive decline rates between the two groups. In a scenario analysis, when all patients receive hippocampal-avoidance PCI (HA-PCI), the model results become near cost effective with PCI due to presumed lower rate of cognitive decline (ICER $129,307 per QALY gained). If HA-IMRT with memantine was also utilized for salvage treatment in all patients in the MRI surveillance group with the assumption above, PCI was found to be cost effective ($88,096 per QALY gained). In addition, the total radiation therapy reimbursement per episode suggested by APM for radiation therapy for brain metastases ($10,783) is almost identical to the current Medicare reimbursement rate for 10 fractions with HA-IMRT ($10,445). Thus, this scenario analysis also reflected the use of the APM.PCI was not cost effective compared to MRI surveillance alone due to the neurocognition decline impact of PCI based on available evidence. HA-PCI may be a potential cost-effective strategy for ES-SCLC, with expected confirmation following the ongoing SWOG MAVERICK trial, which includes assessments of cognitive function.

Patterns of Care for Brain Metastasis Radiotherapy (RT) in an Integrated Healthcare System: Does Increasing Utilization of Stereotactic Radiosurgery (SRS) Compared to Whole Brain RT (WBRT) Lead to Excessive Use at the End of Life (EOL)?

Previous study at our institution showed a high rate of WBRT received near the EOL. Growing evidence of improved neurocognitive and quality of life (QOL) outcomes without compromise of local control has led to increased advocacy of SRS for brain metastasis compared to WBRT. We examine our trend in patterns of care for non-small cell lung cancer (NSCLC) patients, including palliative care/hospice enrollment, and whether rate of brain metastasis RT near EOL has changed with evolving practices.Central Cancer Registry identified 4765 patients diagnosed with NSCLC at 2 facilities from 2007-17. Patients with brain metastasis were identified using natural language processing of imaging reports and confirmed by image review. Patient clinical/treatment characteristics were obtained through database linkage and manual chart abstraction. Bivariate and multivariate logistic regression analyses were performed.Of 792 patients with brain metastasis, 537 received at least 1 fraction of RT. SRS as initial treatment increased over time, comprising 10% of cases in 2007-11, 22% in 2012-16, and 52% in 2017. Number of lesions initially treated with SRS also increased: among patients with 1-3 lesions, 15% in 2007-11, 33% in 2012-16, and 68% in 2017 received SRS upfront, while 3%, 13%, and 33% of patients with 4-9 lesions received it in the respective periods. SRS for patients with 10-19 lesions was minimal, though half received SRS upfront in 2017. The proportion of patients receiving WBRT near EOL was substantial and higher than for SRS. Of 244 patients with 1-3 lesions, 64 (26%) died within 30 days of RT, comprising 25% of patients receiving WBRT and 11% receiving SRS. Older age, male sex, increasing number of extracranial metastatic sites, and inpatient consultation were independent predictors of death within 30 days of RT. Patients enrolled in palliative care/hospice were less likely to die within 30 days of RT (P = 0.048) and less likely to die as inpatients (P < 0.01).SRS utilization increased from 2007-17, particularly among patients with 1-9 lesions. Despite this increase, the proportion of patients receiving SRS near EOL was low and much less than the proportion receiving WBRT, suggesting that patients were selected well for SRS but not WBRT. As SRS is associated with shorter treatment time and lower toxicity compared to WBRT, greater SRS utilization in those without poor predictive factors may maintain QOL without risking excessive use at EOL. Early palliative care and expanding indications for upfront SRS may be considerations for decreasing the risk of treatment near the EOL.A.D. Batra: None. S. Yang: None. C. Zheng: None. D. Jiang: None. J. Rahimian: None. M.R. Girvigian: None. M.K. Gould: None. J.J. Ryoo: None.

A new prognostic score for predicting survival in patients treated with robotic stereotactic radiotherapy for brain metastases

The study aimed to analyze potential prognostic factors in patients treated with robotic radiosurgery for brain metastases irrespective of primary tumor location and create a simple prognostic score that can be used without a full diagnostic workup. A retrospective analysis of 142 patients with 1–9 brain metastases treated with stereotactic radiosurgery (1–4 fractions) was performed. Volumes of all lesions were calculated using linear dimensions of the tumors (CC, LR, AP) and 4/3*π*(CC/2)*(LR/2)*(AP/2) formula. Kaplan–Meier method and log-rank test were used to analyze survival. Variables significantly associated with overall survival in univariate analysis were included in Cox multivariate analysis. The validity of the model was tested with the bootstrap method. Variables from the final model were used to construct a new prognostic index by assigning points according to the impact of a specific variable on overall survival. In the multivariate analysis, four factors: Karnofsky Performance Status (p = 0.000068), number of brain metastases (p = 0.019), volume of the largest lesion (p = 0.0037), and presence of extracerebral metastases (p = 0.0017), were independent predictors of survival. Total scores ranged from 0 to 12 points, and patients were divided into four groups based on median survival of each subgroup: 0–1 points—18.8 months, 2–3 points—16.9 months, 4–5 points—5.6 months, and ≥ 6 points—4.9 months (p < 0.001). The new prognostic index is simple to calculate. It has a strong prognostic value in a heterogeneous population of patients with a various number of brain metastases, but its value requires confirmation in another cohort.

Diagnosis and management of gestational trophoblastic disease: 2021 update.

Gestational trophoblastic disease (GTD) arises from abnormal placenta and is composed of a spectrum of premalignant to malignant disorders. Changes in epidemiology of GTD have been noted in various countries. In addition to histology, molecular genetic studies can help in the diagnostic pathway. Earlier detection of molar pregnancy by ultrasound has resulted in changes in clinical presentation and decreased morbidity from uterine evacuation. Follow‐up with human chorionic gonadotropin (hCG) is essential for early diagnosis of gestational trophoblastic neoplasia (GTN). The duration of hCG monitoring varies depending on histological type and regression rate. Low‐risk GTN (FIGO Stages I–III: score <7) is treated with single‐agent chemotherapy but may require additional agents; although scores 5–6 are associated with more drug resistance, overall survival approaches 100%. High‐risk GTN (FIGO Stages II–III: score ≥7 and Stage IV) is treated with multiagent chemotherapy, with or without adjuvant surgery for excision of resistant foci of disease or radiotherapy for brain metastases, achieving a survival rate of approximately 90%. Gentle induction chemotherapy helps reduce early deaths in patients with extensive tumor burden, but late mortality still occurs from recurrent treatment‐resistant tumors.

Myasthenia Gravis Lambert-Eaton overlap syndrome induced by nivolumab in a metastatic melanoma patient.

Myasthenia gravis (MG) Lambert-Eaton (LE) overlap syndrome is a rare condition. Here, we describe the first caseof MG-LE overlap syndrome revealed by the anti-programmed cell death 1 inhibitor, nivolumab, in a patient treatedfor metastatic melanoma. Three months after receiving nivolumab and 1 month after brain metastasis radiotherapy, our patient developedgeneralized fatigue with intermittent ptosis and swallowing difficulty suggesting a myasthenic syndrome.Electromyogram findings, anti-acetylcholine receptor, and anti-calcium channel antibodies levels were consistentwith an immune-related myasthenic syndrome with specific features for both MG and LE syndromes.Immunotherapy with nivolumab was stopped. Patient was treated with systemic immunosuppressive and anti-cholinesterasedrugs, with remarkable improvement of his neurological symptoms. Prolonged partial remission wasobtained for his metastatic melanoma without need for a third-line treatment. Two years later, a relapse of hismyasthenic symptoms was observed along with new neurological symptoms related to brain radiation necrosis. We describe the first case of MG-LE overlap syndrome diagnosed after anti-PD1 immunotherapy for metastaticmelanoma, which appeared after radiation therapy and then relapsed after brain radiation necrosis. Wehypothesized a role for brain inflammation as a trigger for MG-LE onset. Neuro-muscular junctions disease inducedor revealed by checkpoint inhibitors can be challenging and requires long-term follow-up.

Performance of Conventional and Machine-Learning Approaches for the Diagnosis of Tumor Recurrence on MRI after Radiation Therapy of Brain Metastases

Objective: To compare the performance of conventional and machinelearning approaches for the diagnosis of tumor recurrence after radiation therapy of brain metastases. Methods: 184 symptomatic patients with solitary metastatic brain lesions treated with radiation therapy were enrolled in a monocentric retrospective study from June 2013 to May 2018. The diagnosis was tumor recurrence (n=71) and radiation necrosis (n=113) using as reference standard expert-consensus derived from pathology and long-term follow-up. 37 potential predictors were recorded at the time of radiological progression (7-15 months after therapy): 6 clinical features and 31 imaging features including 20 radiomics features derived from standard of care 3D T1-gadolinium sequences. We compared four approaches (A, B, C, D): expert report using MRI sequences without (A) and with delayedcontrast MRI (TRAM) sequences (B), 11 non-Radiomics imaging features alone (C) and a signature combining variables selected using unsupervised machinelearning algorithms (D), training:validation sets: n=144:40 pts). Results: Overall (n=184), approaches B and C (using TRAM sequence alone) reached comparable performances with respective AUCs [95% CI] of 78.7% [72.3%-85.1%] and 76.8% [70.3%-83.3%]. Both significantly outperformed approach A with AUC [95% CI] of 57.4% [50.7%-64.1%] (DeLong’s test, p-value=10-7). In the validation set (n=40), the signature reached an AUC [95% CI] of 92% [87%-97%]. Conclusion: A quantitative analysis of TRAM sequence seems the best approach for the diagnosis of recurrent tumor after radiation therapy. It is parsimonious, objective and less time-consuming than interpreting all sequences. A signature derived from the analysis of standard of care 3D T1- gadolinium sequence showed promising results that warrant prospective validation.

RADI-20. Brain metastasis treatment with high energy radiotherapy and Cherenkov radiation-activated phototherapy

Abstract Radiation therapy is a mainstay in the treatment of brain metastasis, yet some tumors are resistant, and elsewhere brain recurrence outside the radiation field is common. Phototherapy using UV light-activated compounds can both kill cancer cells directly and trigger an immune response to extend tumor control. Poor penetration depth of ultraviolet light, however, has limited this treatment to superficial tumors. High-energy photon beams create high energy electrons within the patient which in turn produce Cherenkov radiation in the UV spectrum while traveling through tissue. Given that this Cherenkov radiation is generated deep within the patient and has the ability to activate photosensitive compounds, we therefore developed a platform to test this phenomenon to enhance radiation therapy for brain metastasis. We first tested UV-activated psoralen derivatives in combination with UV light in vitro for activity against murine 4T1 breast cancer cells, and then irradiated an ex vivo organotypic brain slice platform using a high energy linear accelerator to generate Cherenkov radiation. We tested the survival of 4T1 cells expressing fluorescent and bioluminescent reports in the presence and absence of these psoralen compounds in this ex vivo brain metastasis model. 8-methoxypsoralen (8-MOP) and 4’-Aminomethyltrioxsalen hydrochloride (AMT) both showed 365nm UVA light-specific cell killing in vitro. We optimized AMT cell loading (1 hour) and concentrations [1μM] AMT to maximize cytotoxicity. Testing of AMT using the organotypic brain slice platform and high-energy irradiation to generate Cherenkov-UV light demonstrated similar enhanced cell death of 4T1 cells despite high baseline levels of radiation-induced tumor cell kill. Cherenkov radiation-induced photo-activation of AMT improved cell killing in an ex vivo model of breast cancer brain metastasis. This application holds promise for the re-treatment of refractory tumors with high-energy, low dose radiation, and enhanced elsewhere brain metastasis control through activation of the immune system.

RADI-09. Clinical factors associated with death after radiotherapy for brain metastases

IntroductionIt can be challenging to accurately identify patients with brain metastases who have very poor prognosis and are unlikely to benefit from radiation (RT). We characterized factors of patients who died within 30 days of receiving RT for brain metastases.MethodsPatients who received whole brain RT (WBRT) or stereotactic radiosurgery (SRS) for brain metastases between 1/1/2017–9/30/2020 at a single institution were identified. Patient, tumor, treatment, and death variables were collected. Characteristics between those who did and did not die within 30 days were compared using the Wilcoxon Rank-Sum or Chi-Square test. Survival was estimated with Kaplan-Meier method.Results636 patients received WBRT (n=117) or SRS (n=519). Median age was 61. Median survival was 6 months (95% CI 5–7 months). 75 (12%) died within 30 days of RT. Patients who died within 30 days had worse median KPS (50 vs 80, p<0.001). A higher proportion who died within 30 days had innumerable intracranial metastases (45% vs 11%, p<0.001), leptomeningeal disease (16% vs 5%, p<0.001), and higher burden of neurologic symptoms at presentation (seizures (12% vs 4%, p=0.003); cranial neuropathies (32% vs 9%, p<0.001); motor/sensory deficits (51% vs 29%, p<0.001); altered mentation (60% vs 26%, p<0.001); headaches (48% vs 30%, p<0.001); steroid use (68% vs 48%, p<0.001)). Patients who died within 30 days had progressive extracranial disease (intrathoracic: 87% vs 50%; spinal: 57% vs 18%; liver/adrenal: 60% vs 24%), p<0.001. More patients who died within 30 days received inpatient RT (39% vs 4%, <0.001) and did not complete RT (24% vs 1%, p<0.001).DiscussionPatients who died within 30 days of RT had worse KPS, intracranial/extracranial disease burden, and neurologic symptoms. Future analyses will assess whether these factors can inform a prognostic model to identify patients with poor prognosis who may be appropriate for supportive care alone.