Eureka Build-a-thon

Living With Meningioma

Submitted by William Chen on September 11, 2023 - 11:47am Last revised by Kathryn Kemper on October 6, 2023 - 12:00pm.
Proposal Status: 
Awarded

 

    • TEAM LEADER (UCSF PI Status):
      • William C Chen MD
    • TEAM LEADER CONTACT (Email & Phone Number):
    • TEAM MEMBERS (Teams are highly encouraged to have a non-researcher stakeholder)
      • William C Chen MD
      • David R Raleigh MD PhD
      • John de Groot MD
      • Steve Braunstein MD PhD
      • Minh Nguyen BS
      • Nicole Willmarth PhD (Patient advocate and Chief Mission Officer, American Brain Tumor Association)
    • DEPARTMENT
      • Radiation Oncology and Neurosurgery
  • RESEARCH QUESTION

We aim to leverage the unique Eureka platform to reach a broad population of meningioma survivors and enroll them into our Living With Meningioma cohort. We will perform annual questionnaires investigating quality of life, symptom burden, engagement with and barriers to care, and lasting effects of treatment for this common tumor, over a study period of 5 years. We will also recruit normal control participants as a control arm as comparison.

  • SPECIFIC AIMS (1/2 page)

Meningioma is the most common primary intracranial neoplasm, accounting for approximately 40% of newly diagnosed primary brain tumors and with approximately 42,000 new cases annually in the United States1. The estimated prevalence of persons living with meningioma in the United States is between 170,000 and 210,000, although this number may be much higher, up to 400,000 or more, based upon incidence and survival rates2. The primary treatment of meningioma includes surgical resection and/or ionizing radiation therapy, as systemic therapies remain ineffective or experimental. Most WHO grade 1 meningiomas can be effectively treated with surgery or radiotherapy, but many WHO grade 2 or grade 3 meningiomas are resistant to treatment and cause significant neurological morbidity and mortality3. With appropriate treatment and surveillance, however, most meningioma patients have a long survival horizon, with a 10-year relative survival of approximately 83-87% compared to age-matched normal controls1. Yet, despite being the most common primary brain tumor, there exists minimal data on the long-term quality of life, side effects of therapy, and survivorship considerations for patients living with meningioma. The scant existing literature4 indicate that survivors living with meningioma experience lasting symptoms of disease and effects of treatment, long after diagnosis and therapy, and also experience gaps in communication and information about their disease process and access to survivorship resources. In particular, little to no data is available to guide providers, patients, and caregivers, about the long-term risks and impacts of intracranial radiation therapy for meningioma5. The aim of this proposed study is to leverage the unique Eureka platform to engage a broad target population of persons living with meningioma, initially in California but eventually nationwide, in order to begin to study and improve our understanding the long-term impacts of this disease and its treatment on the lives and well-being of meningioma survivors.

  • STUDY PROCEDURES AND TIMEPOINTS (1/2 page)

Living With Meningioma will prospectively enroll participants with a self-reported diagnosis of meningioma, at any timepoint of their treatment and survivorship journey and will follow them longitudinally for a period of 5 years. Initially, the target population is all adult persons age 18 or older with a diagnosis of meningioma residing in the state of California. In the interest of capturing as broad a target population as possible, we will utilize self-report of a meningioma diagnosis, given the difficulty of obtaining detailed medical records for persons throughout California who may have been treated many years ago at non-UCSF medical centers with varying medical record systems. Exclusion criteria include the inability to provide informed consent and the inability to interact with the Eureka platform to successfully complete the study questionnaires. Potential participants will be identified via mailing lists, listservs and contact information of brain tumor survivors available through the American Brain Tumor Society, as well as through lists of meningioma patients treated at UCSF. In the future, as the study expands, we will seek out brain tumor survivorship groups in major metropolitan centers, seek out participation from collaborators at other medical centers, and also utilize social media messaging and ads in order to identify more participants. Prospective participants meeting eligibility will be initially screened by self-report of a diagnosis of meningioma at any time in their life. We will initially target a pilot sample size of 250 participants recruited within then 1st year of the study, but eventually will expand to a target of 2,500 participants, or ~0.5%-1% of meningioma survivors in the United States. An incentive of $10 will be offered for completion of each set of annual surveys.

Simultaneous to recruiting of meningioma survivors as above, we will seek to recruit control participants of similar age and characteristics in a 2:1 ratio favoring meningioma survivors, using the method of recruitment by referral of friends and family members. 50% of meningioma survivors enrolled in the study will be asked to identify a friend or family member of similar age without a known meningioma diagnosis, to themselves to be enrolled in Living With Meningioma as a control subject; the number of meningioma survivor participants asked to refer a friend/family member can be uptitrated depending upon the successful referral and enrollment rate of normal controls. An incentive of $10 will be offered for completion of each set of annual surveys, and a referral incentive of $5 for successful referral of a normal control.

The following questionnaires will be performed for meningioma survivors: a modified meningioma specific version of the FOCUS (Follow Up Care Among Survivors) survey6 which is an established survey for cancer survivors collecting comprehensive data on symptom burden, cancer history, treatment, and follow up, second cancers, and quality of life. The questions will be modified to be meningioma specific and the questionnaire shortened. The EORTC QLQ-C30, Meningioma-specific quality of life (MQOL)7, and BN20 (brain specific) quality of life questionnaires will be administered, along with the COST-FACIT financial toxicity survey, and Decision Regret Scale (if patients have undergone a treatment); each of these are 1 page long and fast to complete. Normal controls will be administered the same questionnaires, except altered to not ask questions related to diagnosis or treatment of meningioma. The quality of life, symptom burden, and financial toxicity questionnaires will be administered once annually for the study duration. If possible, patient information will be retrospectively linked once annually with the California and National Death Registry to identify patients who pass away during the duration of the study.

  • FEASIBILITY (1 paragraph) – Please comment on the feasibility of using Eureka for this study and feasibility of executing the study once built.

The Eureka platform represents an ideal platform for reaching participants and administering the questionnaires, all of which are amenable to digitizing. The study team members are committed to the creation of a UCSF multidisciplinary meningioma program aiming to improve the care of meningioma patients and survivors, and are in the process of hiring a full time clinical research coordinator dedicated to meningioma related trials. Living With Meningioma will play a central role in studying the long term impacts of this disease on patients.

  • FUNDABILITY (1 paragraph) – What is your current funding for this project, or if currently unfunded, how will this support funding applications?

The project is currently funded by career development funds available to the team leader, William Chen. Depending on the success of the pilot component of this study, further funding will be sought through meningioma related philanthropic funds and brain tumor research grants.

  • PROFESSIONAL DEVELOPMENT (1 paragraph) – How will this project support the professional development of the team leader and/or team members?

William Chen is a Clinical Instructor in Radiation Oncology who is in his first year out of training, and is also a K12 fellow through the Helen Diller Family Cancer Center. This project represents an integral component of his development as a clinician scientist as he seeks to achieve independent funding, and to establish a research program studying meningioma. Living With Meningioma will be a major piece of a larger plan to establish a meningioma program at UCSF which will aim to bring the latest developments in research to the bedside through clinical trials. Other trials that are in development include a trial studying shortening of radiation courses for meningioma patients, a trial studying improvements in personalization of radiation dose for meningioma patients, and a prospective registry of genomic and blood based biomarkers for meningioma patients.

  • IMPACT (1 paragraph) – What improvements will result if your research succeeds (e.g., what are the public health implications or community benefits)?

Despite being the most common primary intracranial tumor, few studies have examined long term quality of life, symptom burden, engagement in care, barriers to care, and lasting effects of surgery and/or radiotherapy, among meningioma survivors. Living With Meningioma using the unique Eureka platform would allow us to study these questions in a large cohort of meningioma survivors in a cross sectional as well as longitudinal fashion. In addition to these question, several additional questions will be able to be studied: 1) what is the rate of guideline-adherent8 follow up with MRI imaging in long term meningioma survivors, given the propensity for late recurrence of these tumors, 2) after tumor recurrence, what is the change in disease and treatment burden on meningioma survivors, 3) if patient information can be linked to death registries, capture of the rate of all-cause mortality among long term meningioma survivors in a contemporary cohort. All of these questions will help to guide future clinical trials and quality improvement efforts in order to better understand and deliver the best care for our patients living with this common brain tumor. 

 

References:

1.        Ostrom QT, Price M, Neff C, et al. CBTRUS Statistical Report: Primary Brain and Other Central Nervous System Tumors Diagnosed in the United States in 2015-2019. Neuro Oncol. 2022;24(5):v1-v95. doi:10.1093/neuonc/noac202

2.        Wiemels J, Wrensch M, Claus EB. Epidemiology and etiology of meningioma. J Neurooncol. 2010;99(3). doi:10.1007/s11060-010-0386-3

3.        Brastianos PK, Galanis E, Butowski N, et al. Advances in multidisciplinary therapy for meningiomas. Neuro Oncol. 2019;21:I18-I31. doi:10.1093/neuonc/noy136

4.        Nassiri F, Suppiah S, Wang JZ, et al. How to live with a meningioma: Experiences, symptoms, and challenges reported by patients. Neurooncol Adv. 2020;2(1). doi:10.1093/noajnl/vdaa086

5.        Henzel M, Fokas E, Sitter H, Wittig A, Engenhart-Cabillic R. Quality of life after stereotactic radiotherapy for meningioma: A prospective non-randomized study. J Neurooncol. 2013;113(1). doi:10.1007/s11060-013-1099-1

6.        Kent EE, Arora NK, Rowland JH, et al. Health information needs and health-related quality of life in a diverse population of long-term cancer survivors. Patient Educ Couns. 2012;89(2). doi:10.1016/j.pec.2012.08.014

7.        Baba A, Saha A, McCradden MD, et al. Development and validation of a patient-centered, meningioma-specific quality-of-life questionnaire. In: Journal of Neurosurgery. Vol 135. ; 2021. doi:10.3171/2020.11.JNS201761

8.        Goldbrunner R, Minniti G, Preusser M, et al. EANO guidelines for the diagnosis and treatment of meningiomas. Lancet Oncol. 2016;17(9):e383-e391. doi:10.1016/S1470-2045(16)30321-7

 

Comments

Alexis Beatty - September 13, 2023 - 10:32am

Seems like a good use of Eureka to recruit a broad population beyond just what is accessible at UCSF. How will you drive recruitment?

How will you address the possibility of confounding when analyzing any differences between meningioma and control patients?

Would you need to capture any other data that may be possible through Eureka connections? e.g., wearable devices, EHR data via FHIR?

William Chen - September 14, 2023 - 10:25pm

Thank you very much for the comments! To start off, we would use lists of brain tumor survivors and caregivers provided by the American Brain Tumor Association, which maintains a large network of donors, supporters, and patients, to drive recruitment among a relatively motivated and engaged population. The monetary incentive is also designed to increase interest. In the future we may also consider trying targeted ads through social media to reach an even broader population. 

Regarding the issue of confounding, the FOCUS questionnaire does collect basic self reported information about level of comorbidity, demographics and socioeconomics, etc, which may allow for statistical approaches to perform matching or multivariate adjustment to help account for confounding. 

Thank you for the question about other Eureka capabilities. I don't anticipate collecting wearables data. EHR data via FHIR is intriguing, and I confess I don't know much about what is possible in this regard via Eureka, but I'd love to learn more about this! 

Kathryn Kemper - September 13, 2023 - 4:08pm

Thanks for submitting this great proposal and novel idea for using Eureka.

I'm curious if there is any reason to limit the cohort to adults living in California or if there is interest in expanding nationally?

I agree with the question above about possible confounding between meningioma and control patients. Are there other control groups the researchers have considered who are non-related to meningioma patients? Since many of the surveys are specific to survivorship and living with meningioma, I'm curious if you might consider using another population of survivors as a control group for better comparison across survey results.

William Chen - September 14, 2023 - 10:38pm

Thanks so much for the great comments! Regarding California, this was our initial concept for this protocol prior to learning about Eureka. It's certainly true that it seems like there may not be a good reason to limit the Eureka platform to California, and perhaps starting nationwide may be the way to go. Certainly eventually we always would have wanted to expand to reach a broader population. 

Both comments raise good points about confounding. I agree use of friends and relatives as normal controls is a practical choice for recruitment but could lead to confounding. On the other hand, some studies have shown that use of friend/family network controls result in controls that are naturally more similar to study subjects. Indeed, some studies find friend referrals to be more closely similar than family, which seems to reflect the natural tendency for social networks to be composed of similar people in age and other characteristics. In some ways this could lead to some natural "pairing" of subjects. In other ways you are right that there may be confounding that could be difficult to control for -- more so since not every subject will have a matching self-referred normal control. We did think about using another brain tumor or cancer survivor type as a control group, but our study question is really to compare meningioma survivors to "healthy normal" controls, and other brain tumor survivors or cancer survivors may in fact experience greater symptom burdens than meningioma patients. One alternative to all of the above could perhaps simply be random recruitment through social media of "normal controls", although this may also introduce self-selection bias of persons willing to answer a social media ad to participate as a control. Perhaps in some ways the subject referred control subject, who may be participating due to the request of a friend or family member when he/she may not have otherwise, may be less biased in that regard.  I'd welcome any/all suggestions/prior experience with normal control arms in studies like this. Thanks again!