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

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.

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Advances in radiotherapy for brain metastases

Neuro-Oncology Advances ◽

10.1093/noajnl/vdab126 ◽

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.

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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

Journal of Clinical Oncology ◽

10.1200/jco.2000.18.19.3400 ◽

2000 ◽

Vol 18 (19) ◽

pp. 3400-3408 ◽

Cited By ~ 159

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.

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Comparative study of psychometric properties of three assessment tools for degenerative rotator cuff disease

Clinical Rehabilitation ◽

10.1177/0269215518796888 ◽

2018 ◽

Vol 33 (2) ◽

pp. 277-284 ◽

Cited By ~ 3

Author(s):

Etienne James-Belin ◽

Anne Laure Roy ◽

Sandra Lasbleiz ◽

Agnès Ostertag ◽

Alain Yelnik ◽

...

Keyword(s):

Rotator Cuff ◽

Psychometric Properties ◽

Intraclass Correlation ◽

Assessment Tools ◽

University Hospital ◽

Rotator Cuff Disease ◽

Retest Reliability ◽

Good For ◽

Test Retest Reliability ◽

Improvement Score

Objective: To compare psychometric properties of Disabilities of the Arm, Shoulder and Hand (DASH) questionnaire, Shoulder Pain and Disability Index (SPADI) and Constant–Murley scale, in patients with degenerative rotator cuff disease (DRCD). Design: Longitudinal cohort. Setting: One French university hospital. Methods: The scales were applied twice at one-week interval before physiotherapy and once after physiotherapy two months later. The perceived improvement after treatment was self-assessed on a numerical scale (0–4). The test–retest reliability of the DASH, SPADI and Constant–Murley scales was assessed before treatment by the intraclass correlation coefficient (ICC). The responsiveness was assessed by the paired t-test ( P < 0.05) and standardized mean difference (SMD). The correlation between the percentage of variation in scale scores and the self-assessed improvement score after treatment was measured by the Spearman coefficient. Results: Fifty-three patients were included. Twenty-six only were available for reliability. The test–retest reliability was very good for the DASH (ICC = 0.97), SPADI (0.95) and Constant–Murley (0.92). The scale score was improved after treatment for each scale ( P < 0.05). The SMD was moderate for the DASH (0.56) and SPADI (0.56) scales, and small for the Constant–Murley (0.44). The correlation between the percentage of variation in scores and self-assessed improvement score after treatment was high, moderate and not significant for the SPADI (0.59, P < 0.0001), DASH (0.42, P < 0.01) and Constant–Murley scales, respectively. Conclusion: The test–retest reliability of the DASH, SPADI and Constant–Murley scales is very good for patients with DRCD. The highest responsiveness was achieved with the SPADI.

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

Tumori Journal ◽

10.1177/030089160509100408 ◽

2005 ◽

Vol 91 (4) ◽

pp. 325-330 ◽

Cited By ~ 19

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.

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Toward Precision Medicine in Brain Metastases

Seminars in Neurology ◽

10.1055/s-0038-1627469 ◽

2018 ◽

Vol 38 (01) ◽

pp. 095-103 ◽

Cited By ~ 3

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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Allodynography: Reliability of a New Procedure for Objective Clinical Examination of Static Mechanical Allodynia

Pain Medicine ◽

10.1093/pm/pnz045 ◽

2019 ◽

Vol 21 (1) ◽

pp. 101-108

Author(s):

Tara L Packham ◽

Claude J Spicher ◽

Joy C MacDermid ◽

Norman D Buckley

Keyword(s):

Clinical Examination ◽

Clinical Assessment ◽

Mechanical Allodynia ◽

Intraclass Correlation ◽

Assessment Tools ◽

Measurement Properties ◽

Rater Reliability ◽

Retest Reliability ◽

Static Mechanical ◽

Test Retest Reliability

Abstract Objective There is a need for reliable and valid clinical assessment tools for quantifying allodynia in neuropathic pain. Allodynography has been proposed as a useful standardized procedure for clinical assessment of mechanical allodynia. This study (www.clinicaltrials.gov NCT02070367) undertook preliminary investigation of the measurement properties of allodynography, a new standardized clinical examination procedure for mapping the area of cutaneous allodynia. Methods Persons with pain in one upper extremity after complex regional pain syndrome, a peripheral nerve injury, or who had recently experienced a hand fracture were recruited for assessment of static mechanical allodynia (based on perception of a 15g force stimulus delivered by Semmes-Weinstein monofilament #5.18 as painful) by two raters at baseline; the assessment was repeated one week later. Results Single-measures estimates suggested inter-rater reliability for allodynography was excellent at an intraclass correlation coefficient (ICC) of 0.97 (N = 12); test–retest reliability was also excellent at ICC = 0.89 (N = 10) for allodynography (P < 0.001 for both). Confidence intervals’ lower bounds confirm inter-rater reliability as excellent (0.90) but were less definitive for test–retest (0.59). Conclusions This preliminary study supports the inter-rater and test–retest reliability of allodynography. Studies on larger samples in multiple contexts and reporting other measurement properties are warranted.

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Validating a Series of Photo-Numeric Rating Scales for Use in Facial Aesthetics Using Statistical Analysis of Intra- and Inter-Rater Reliability

Aesthetic Surgery Journal Open Forum ◽

10.1093/asjof/ojab039 ◽

2021 ◽

Author(s):

Z Paul Lorenc ◽

Derek Jones ◽

Jeongyun Kim ◽

Hee Min Gwak ◽

Samixa Batham ◽

...

Keyword(s):

Clinical Significance ◽

Rating Scales ◽

Objective Assessment ◽

Intraclass Correlation ◽

Unmet Need ◽

Assessment Tools ◽

Facial Aesthetics ◽

Rater Reliability ◽

Retest Reliability ◽

Test Retest Reliability

Abstract Background Growing demand for minimally invasive aesthetic procedures to correct age-related facial changes and optimize facial proportions has been met with innovation, but has created an unmet need for objective assessment tools to evaluate results empirically. Objectives The purpose of this study is to establish the intra- and inter-rater reliability of ordinal, photonumeric, 4- or 5-point rating scales for clinical use to assess facial aesthetics. Methods Board-certified plastic surgeons and dermatologists (3 raters) performed live validation of jawline contour, temple volume, chin retrusion, nasolabial folds, vertical perioral lip lines, midface volume loss, lip fullness, and crow’s feet dynamic- and at rest- rating scales over 2 rounds, 2 weeks apart. Subjects selected for live validation represented the range of scores and included 54-83 subjects for each scale. Test-retest reliability was quantitated through intra- and inter-rater reliability, determined from the mean weighted kappa and Round 2 Intraclass Correlation Coefficients (ICC), respectively. The clinical significance of a one grade difference was assessed through rater comparison of 31 pairs of side-by-side photographs of subjects with the same grade or a different grade on the developed scales. Results The study demonstrated substantial to near-perfect intra-rater and inter-rater reliability of all scales when utilized by trained raters to assess a diverse group of live subjects. Furthermore, the clinical significance of a 1-point difference on all the developed scales was established. Conclusions The high test-retest reliability and intuitive layout of these scales provide an objective approach with standardized ratings for clinical assessment of various facial features.

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The Test of Orientation for Rehabilitation Patients: Test-Retest Reliability

The Occupational Therapy Journal of Research ◽

10.1177/153944929201200304 ◽

1992 ◽

Vol 12 (3) ◽

pp. 172-185 ◽

Cited By ~ 1

Author(s):

Jean C. Deitz ◽

Vicky S. Tovar ◽

Clara Beeman ◽

Deborah W. Thorn ◽

Michael S. Trevisan

Keyword(s):

Brain Injury ◽

Repeated Measures ◽

Brain Injuries ◽

Intraclass Correlation ◽

Retest Reliability ◽

Reliability Estimates ◽

Injury Group ◽

Temporal Continuity ◽

Test Retest Reliability ◽

The Brain

The Test of Orientation for Rehabilitation Patients was developed for assessing the orientation of inpatients with brain injuries in rehabilitation settings. The test is composed of 46 items grouped into five domains of orientation: 1) Person and Personal Situation, 2) Place, 3) Time, 4) Schedule, and 5) Temporal Continuity. Test-retest reliability and magnitudes of difference between scores on test and retest were examined using subgroups of 30 rehabilitation patients with brain injuries and 32 rehabilitation patients without brain injuries. The interval between test and retest ranged from 3 to 5 days. Test-retest reliability estimates (using the two-way random effects repeated measures model of the intraclass correlation coefficient) for the total test scores were good (r = .85) to excellent (r = .95) for the non-brain-injury and brain-injury groups, respectively. Reliability coefficients for the domain scores were higher for the brain-injury group than the non-brain-injury group. However, when agreements between test and retest scores were examined, the non-brain-injury group showed greater stability.

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PS1 - 159 A Case of Intracranial Metastases from Renal Pelvic Carcinoma and Review of Literature

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/cjn.2016.347 ◽

2016 ◽

Vol 43 (S4) ◽

pp. S7-S7

Author(s):

A. Ghare ◽

F. Haji ◽

M. Boulton

Keyword(s):

Brain Metastases ◽

Case Reports ◽

Transitional Cell ◽

Whole Brain Radiotherapy ◽

Healthcare Team ◽

Primary Cancer ◽

Intracranial Metastasis ◽

Brain Radiotherapy ◽

Intracranial Metastases ◽

The Brain

Transitional cell carcinoma (TCC) of the renal pelvis is a rare urological malignancy, with only a handful of cases of metastases to the brain reported in literature. We aim to present a case of intracranial metastasis in a female patient with history of renal pelvic carcinoma, and review existing literature of brain metastases from renal pelvic TCC. Methods: We searched PubMed, EMBASE, and MEDLINE from 1966 to January 2016 for published case reports written in English. Results: Five published case reports describe intracranial metastases from renal pelvic TCC. Our case is a 56-year-old woman with known high grade renal pelvic carcinoma and pulmonary metastases, who presented nine years after her initial diagnosis with mild left side weakness and headaches. She was found to have two lesions in the right cerebral hemisphere and underwent surgical resection of the larger right frontal lobe mass. Her neurologic symptoms improved postoperatively. She declined whole brain radiotherapy and remains stable at 6 months’ follow-up. This is the first published case of presentation of brain metastases from pelvic TCC more than 12 months after diagnosis of the primary cancer. Conclusion: There is minimal literature of renal pelvic TCC metastasizing to the brain. However, as systemic chemotherapy leads to improved survival from the primary cancer, it is possible for more cases to appear, necessitating increased awareness from the healthcare team.

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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

Neuro-Oncology Advances ◽

10.1093/noajnl/vdz014.043 ◽

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.)

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