scholarly journals TRLS-10. MITIGATING NEUROCOGNITIVE DEFICITS FROM WHOLE-BRAIN RADIOTHERAPY IN PATIENTS WITH NUMEROUS BRAIN METASTASES VIA A NOVEL SUPEROXIDE DISMUTASE MIMETIC: RATIONALE & DESIGN OF A CLINICAL TRIAL

2019 ◽  
Vol 1 (Supplement_1) ◽  
pp. i10-i10
Author(s):  
John Kirkpatrick ◽  
Heather Franklin ◽  
Jordan Torok ◽  
Scott Floyd ◽  
Carey Anders ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Superoxide Dismutase ◽  
Adverse Effects ◽  
Brain Metastases ◽  
Whole Brain Radiotherapy ◽  
Neurocognitive Deficits ◽  
Brain Radiotherapy ◽  
Brain Failure ◽  
The Brain ◽  
Distant Brain Failure

Abstract BACKGROUND: Patients with a large number of brain metastases (BM) and/or micrometastatic disease in the brain present a clinical challenge. While technical innovations in stereotactic radiosurgery (SRS) have extended the number of BM that can be effectively treated, SRS does not treat occult disease and distant brain failure (DBF) post-SRS remains high. Immuno- and targeted therapies show promise in treating metastatic disease to the brain, though response rates are variable. In contrast, whole-brain radiotherapy (WBRT) provides high rates of local control and, compared to SRS, reduces the risk of distant brain failure. Unfortunately, WBRT is also associated with substantial neurocognitive deficits and neither altered fractionation nor the use of available neuroprotectants has adequately addressed this issue. An agent that safely minimizes the adverse effects of WBRT while preserving or enhancing tumor control would provide meaningful clinical benefit. TRIAL DESIGN: BMX-001, a novel Mn-porphyrin superoxide dismutase mimetic, has been shown to protect normal tissues from ionizing radiation in preclinical trials, reducing neurocognitive adverse effects as well as enhancing tumor response. Based on the first-in-human trial of this agent in patients with high-grade gliomas, we have instituted a clinical trial of WBRT +/- BMX-001 in adult patients with more than 10 BM from melanoma, non-small-cell lung, breast and renal cancer. Following a safety lead-in of 5 patients, all of whom will receive WBRT and BMX-001, 69 patients will be randomized to WBRT (3Gy/fraction x 10 fractions) with or without BMX-001 administered subcutaneously before, twice weekly during and once after WBRT (6 injections total.) The primary endpoint is cognition, as measured by the Hopkins Verbal Learning, Trailmaking A/B and Controlled Oral Word Association tests. Secondary endpoints include health-related quality-of-life, overall and progression-free survival, rates of radiation necrosis, DBF and neurologic death. Enrollment began January 2019. (ClinicalTrials.gov Identifier: NCT03608020.)

scholarly journals The Brain Metastases Symptom Checklist as a novel tool for symptom measurement in patients with brain metastases undergoing whole-brain radiotherapy

2016 ◽  
Vol 23 (3) ◽  
pp. 239 ◽  
Author(s):  
D. Rodin ◽  
B. Banihashemi ◽  
L. Wang ◽  
A. Lau ◽  
S. Harris ◽  
...  
Keyword(s):  
Brain Metastases ◽  
Intraclass Correlation ◽  
Whole Brain Radiotherapy ◽  
Assessment Tools ◽  
Symptom Checklist ◽  
Retest Reliability ◽  
Brain Radiotherapy ◽  
Test Retest Reliability ◽  
The Brain ◽  
Responsiveness To Change

Purpose We evaluated the feasibility, reliability, and validity of the Brain Metastases Symptom Checklist (BMSC), a novel self-report measure of common symptoms experienced by patients with brain metastases.Methods Patients with first-presentation symptomatic brain metastases (n = 137) referred for whole-brain radiotherapy (WBRT) completed the BMSC at time points before and after treatment. Their caregivers (n = 48) provided proxy ratings twice on the day of consultation to assess reliability, and at week 4 after WBRT to assess responsiveness to change. Correlations with 4 other validated assessment tools were evaluated.Results The symptoms reported on the BMSC were largely mild to moderate, with tiredness (71%) and difficulties with balance (61%) reported most commonly at baseline. Test–retest reliability for individual symptoms had a median intraclass correlation of 0.59 (range: 0.23–0.85). Caregiver proxy and patient responses had a median intraclass correlation of 0.52. Correlation of absolute scores on the BMSC and other symptom assessment tools was low, but consistency in the direction of symptom change was observed. At week 4, change in symptoms was variable, with improvements in weight gain and sleep of 42% and 41% respectively, and worsening of tiredness and drowsiness of 62% and 59% respectively.Conclusions The BMSC captures a wide range of symptoms experienced by patients with brain metastases, and it is sensitive to change. It demonstrated adequate test–retest reliability and face validity in terms of its responsiveness to change. Future research is needed to determine whether modifications to the BMSC itself or correlation with more symptom-specific measures will enhance validity. 

scholarly journals Advances in radiotherapy for brain metastases

2021 ◽  
Vol 3 (Supplement_5) ◽  
pp. v26-v34
Author(s):  
Vinai Gondi ◽  
Jacquelyn Meyer ◽  
Helen A Shih
Keyword(s):  
Brain Metastases ◽  
Management Strategy ◽  
Metastatic Cancer ◽  
Treatment Options ◽  
Management Strategies ◽  
Whole Brain Radiotherapy ◽  
Brain Radiotherapy ◽  
Contemporary Management ◽  
The Brain ◽  
Systemic Therapies

Abstract 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.

The brain metastasis journey: Experience from patient, caregiver, and physician surveys on diagnosis and treatment of brain metastases.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e14004-e14004
Author(s):  
Albert Eusik Kim ◽  
GI-Ming WANG ◽  
Kristin A Waite ◽  
Scott Elder ◽  
Avery Fine ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Clinical Trials ◽  
Brain Metastases ◽  
Checkpoint Inhibitors ◽  
Treatment Options ◽  
Whole Brain Radiotherapy ◽  
Well Being ◽  
Cross Sectional Survey ◽  
Cross Sectional ◽  
Brain Radiotherapy

e14004 Background: Brain metastases (BM) is one of the most feared complications of cancer due to substantial neurologic sequalae, neuro-cognitive morbidity and grim prognosis. In the past decade, targeted therapies and checkpoint inhibitors have resulted in meaningfully improved overall survival for a minority of these patients. Accordingly, there is a growing need to identify issues surrounding patient survivorship and to standardize physician practice patterns for these patients. To date, there has not been a well-conducted formal study to specifically explore these questions of survivorship and practice standardization for BM patients. Methods: Here, we present results from a cross-sectional survey in which we analyzed responses from 237 BM patients, 209 caregivers, and 239 physicians. Surveys contained questions about BM symptoms, discussion of BM diagnosis by the clinician, psychosocial concerns, available treatment options for BM, BM patient advocacy resources, and BM-specific clinical trials. Results: Our survey revealed compelling findings about current care of BM patients. There were discrepancies in the perceived discussion of the implications of the diagnosis of BM, from the patient/caregiver and physician perspective. Important topics, such as prognosis and worrisome symptoms, were felt to have been discussed more frequently by physicians than by patients or caregivers. In our physician survey, private practice physicians, compared to academic physicians, were significantly more likely to recommend whole brain radiotherapy (61.1 vs 39.7%; p = 0.009). Participation in a clinical trial was one of the least recommended treatment options. Many physicians (59.1% private; 71.9% academic) stated that BM patients in their care are denied participation in a clinical trial, specifically due to the presence of BM. The consensus among physicians, patients and caregivers was that the highest yield area for federal assistance is increased treatment and research funding for BM. Conclusions: Our hope is that these findings will serve as a basis for future quality improvement measures to enhance patient-physician communication and patient well-being, continuing medical education activities detailing latest advances in BM for oncologists, and lobbying efforts to the federal government in prioritizing BM research, clinical trials, and patient survivorship.

Treatment of Brain Metastases of Small-Cell Lung Cancer: Comparing Teniposide and Teniposide With Whole-Brain Radiotherapy—A Phase III Study of the European Organization for the Research and Treatment of Cancer Lung Cancer Cooperative Group

2000 ◽  
Vol 18 (19) ◽  
pp. 3400-3408 ◽  
Author(s):  
Pieter E. Postmus ◽  
Hanny Haaxma-Reiche ◽  
Egbert F. Smit ◽  
Harry J. M. Groen ◽  
Hanna Karnicka ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Brain Metastases ◽  
Response Rate ◽  
Whole Brain Radiotherapy ◽  
Phase Iii ◽  
Time To Progression ◽  
Brain Radiotherapy ◽  
Combined Modality ◽  
Phase Iii Study ◽  
The Brain

PURPOSE: Approximately 60% of patients with small-cell lung cancer (SCLC) develop brain metastases. Whole-brain radiotherapy (WBRT) gives symptomatic improvement in more than 50% of these patients. Because brain metastases are a sign of systemic progression, and chemotherapy was found to be effective as well, it becomes questionable whether WBRT is the only appropriate therapy in this situation. PATIENTS AND METHODS: In a phase III study, SCLC patients with brain metastases were randomized to receive teniposide with or without WBRT. Teniposide 120 mg/m2 was given intravenously three times a week, every 3 weeks. WBRT (10 fractions of 3 Gy) had to start within 3 weeks from the start of chemotherapy. Response was measured clinically and by computed tomography of the brain. RESULTS: One hundred twenty eligible patients were randomized. A 57% response rate was seen in the combined-modality arm (95% confidence interval [CI], 43% to 69%), and a 22% response rate was seen in the teniposide-alone arm (95% CI, 12% to 34%) (P < .001). Time to progression in the brain was longer in the combined-modality group (P = .005). Clinical response and response outside the brain were not different. The median survival time was 3.5 months in the combined-modality arm and 3.2 months in the teniposide-alone arm. Overall survival in both groups was not different (P = .087). CONCLUSION: Adding WBRT to teniposide results in a much higher response rate of brain metastases and in a longer time to progression of brain metastases than teniposide alone. Survival was poor in both groups and not significantly different.

scholarly journals Whole Brain Radiotherapy and RRx-001: Two Partial Responses in Radioresistant Melanoma Brain Metastases from a Phase I/II Clinical Trial

2016 ◽  
Vol 9 (2) ◽  
pp. 108-113 ◽  
Author(s):  
Michelle M. Kim ◽  
Hemant Parmar ◽  
Yue Cao ◽  
Priyanka Pramanik ◽  
Matthew Schipper ◽  
...  
Keyword(s):  
Clinical Trial ◽  
Brain Metastases ◽  
Phase I ◽  
Whole Brain Radiotherapy ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Melanoma Brain Metastases

Re-Irradiation of Brain Metastases and Metastatic Spinal Cord Compression: Clinical Practice Suggestions

2005 ◽  
Vol 91 (4) ◽  
pp. 325-330 ◽  
Author(s):  
Ernesto Maranzano ◽  
Fabio Trippa ◽  
Diamante Pacchiarini ◽  
Luigia Chirico ◽  
Maria Luisa Basagni ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Brain Metastases ◽  
Stereotactic Radiosurgery ◽  
Stereotactic Radiotherapy ◽  
Whole Brain Radiotherapy ◽  
Cord Compression ◽  
Whole Brain ◽  
Brain Radiotherapy ◽  
Radiation Induced ◽  
The Brain

The recent improvements of therapeutic approaches in oncology have allowed a certain number of patients with advanced disease to survive much longer than in the past. So, the number of cases with brain metastases and metastatic spinal cord compression has increased, as has the possibility of developing a recurrence in areas of the central nervous system already treated with radiotherapy. Clinicians are reluctant to perform re-irradiation of the brain, because of the risk of severe side effects. The tolerance dose for the brain to a single course of radiotherapy is 50–60 Gy in 2 Gy daily fractions. New metastases appear in 22–73% of the cases after whole brain radiotherapy, but the percentage of re-irradiated patients is 3–10%. An accurate selection must be made before giving an indication to re-irradiation. Patients with Karnofsky performance status >70, age <65 years, controlled primary and no extracranial metastases are those with the best prognosis. The absence of extracranial disease was the most significant factor in conditioning survival, and maximum tumor diameter was the only variable associated with an increased risk of unacceptable acute and/or chronic neurotoxicity. Re-treatment of brain metastases can be done with whole brain radiotherapy, stereotactic radiosurgery or fractionated stereotactic radiotherapy. Most patients had no relevant radiation-induced toxicity after a second course of whole brain radiotherapy or stereotactic radiosurgery. There are few data on fractionated stereotactic radiotherapy in the re-irradiation of brain metastases. In general, the incidence of an “in-field” recurrence of spinal metastasis varies from 2.5–11% of cases and can occur 2–40 months after the first radiotherapy cycle. Radiation-induced myelopathy can occur months or years (6 months-7 years) after radiotherapy, and the pathogenesis remains obscure. Higher radiotherapy doses, larger doses per fraction, and previous exposure to radiation could be associated with a higher probability of developing radiation-induced myelopathy. Experimental data indicate that also the total dose of the first and second radiotherapy, interval to re-treatment, length of the irradiated spinal cord, and age of the treated animals influence the risk of radiation-induced myelopathy. An α/β ratio of 1.9–3 Gy could be generally the reference value for fractionated radiotherapy. However, when fraction sizes are up to 5 Gy, the linear-quadratic equation become a less valid model. The early diagnosis of relapse is crucial in conditioning response to re-treatment.

Toward Precision Medicine in Brain Metastases

2018 ◽  
Vol 38 (01) ◽  
pp. 095-103 ◽  
Author(s):  
Anna Berghoff ◽  
Priscilla Brastianos
Keyword(s):  
Brain Metastases ◽  
Genetic Divergence ◽  
Metastatic Cancer ◽  
Treatment Strategies ◽  
Whole Brain Radiotherapy ◽  
Genetic Alterations ◽  
Brain Radiotherapy ◽  
Genomic Technologies ◽  
New Treatment ◽  
The Brain

AbstractBrain metastases (BMs) reflect an area of high clinical need, as up to 40% of patients with metastatic cancer will develop this morbid and highly fatal complication. Historically, treatment strategies have relied on local approaches including radiosurgery, whole-brain radiotherapy, and neurosurgical resection. Recently, targeted and immune-modulating therapies have shown promising responses and have been introduced in the clinical management of patients with BMs. Recent improvements in genomic technologies have enriched our understanding of BMs and have demonstrated that BMs present with significant genetic divergence from the originating primary tumor, such that potentially targetable genetic alterations are detected only in the BMs. However, this genetic divergence also results in genetic alterations associated with resistance to targeted therapies. A deeper insight on the genetic alterations of BMs and the interaction with the brain microenvironment will likely reveal new treatment targets, moving toward more precision therapies for patients with BMs.

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