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Table of Contents
EDITORIAL
Year : 2020  |  Volume : 3  |  Issue : 2  |  Page : 31-33

Management of glioma patients during the coronavirus disease 2019 pandemic


Center for Neuro-Oncology, Dana-Farber Cancer Institute; Division of Neuro-Oncology, Brigham and Women's Hospital; Harvard Medical School, Boston, MA, USA

Date of Submission11-May-2020
Date of Acceptance23-May-2020
Date of Web Publication27-Jun-2020

Correspondence Address:
Dr. Patrick Y Wen
Center for Neuro-Oncology, Dana-Farber Cancer Institute, 450 Brookline Avenue, Boston, MA 02215
USA
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/glioma.glioma_10_20

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How to cite this article:
Youssef G, Wen PY. Management of glioma patients during the coronavirus disease 2019 pandemic. Glioma 2020;3:31-3

How to cite this URL:
Youssef G, Wen PY. Management of glioma patients during the coronavirus disease 2019 pandemic. Glioma [serial online] 2020 [cited 2022 Dec 8];3:31-3. Available from: http://www.jglioma.com/text.asp?2020/3/2/31/288175


  Introduction Top


The coronavirus disease 2019 (COVID-19) pandemic caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) has within a period of months affected over 7 million people worldwide and caused over 400,000 deaths. The intense pressure on health-care resources has significantly affected the delivery of care, including the management of brain tumor patients. In this brief article, the issues related to the management of glioma patients during the COVID-19 pandemic will be discussed.

The incidence of SARS-CoV-2 has differed significantly among countries but is likely to have a long-lasting impact on the management of glioma patients. In the short term, especially in countries where the incidence of SARS-CoV-2 has been increasing exponentially, health-care resources have often been overwhelmed. There have been widespread shortages of personal protective equipment and diversion of workforce and resources, especially intensive care beds and ventilators, to treat COVID-19 patients. As a result, the available resources for treating other conditions, including glioma patients, have become limited. At the same time, glioma patients, especially those with high-grade gliomas who are older and often immunosuppressed as a result of chemotherapy or corticosteroids, are potentially at higher risk of a worse outcome if infected with SARS-CoV-2. The challenge is to balance the risks and benefits of treatment and ensure that glioma patients continue to receive optimal care.[1],[2]


  General Considerations Top


In addition to the standard measures of social distancing, frequent hand washing and wearing of face masks, there are specific considerations related to the therapies for glioma patients. The recommendations for individual patients will depend on the specifics related to that patient and should be made in consultation with all the relevant subspecialties. During the pandemic, multidisciplinary tumor boards may no longer be able to meet in person but should continue virtually to ensure the optimal care of patients. The immune system of glioma patients, especially those with glioblastomas, is suppressed and patients often have lymphopenia even before initiating therapy,[3] potentially increasing their risk from SARS-CoV-2. In addition, since corticosteroids can increase immunosuppression and reduce the symptoms of infections such as fever, every effort should be made to wean patients off these medications or at least maintained on the lowest possible dose. For frail elderly patients who are unlikely to benefit significantly from therapy, palliative care only may be appropriate.[4]


  Surgery Top


The initial treatment for all glioma patients is maximal safe resection of the tumor to reduce tumor burden and hopefully prolong survival, relieve symptoms, and provide tissue for histologic and molecular diagnosis. In many countries, elective surgery has been canceled during the peak of the pandemic. This has affected the ability of many institutions to perform operations.[5] The delay in surgery is justifiable for patients with low-grade gliomas where there is less urgency. For glioblastoma patients, surgery should not be delayed.[1] While the goal is maximal safe resection, consideration should be given to the aggressiveness of the surgery and the likelihood of the patient sustaining a significant deficit and requiring prolonged stay in the intensive care unit and hospital.


  Pathologic and Molecular Diagnosis Top


Since tumor histologic grade, determination of isocitrate dehydrogenase (IDH) mutational status, presence of 1p/19q codeletion, and methyl guanine methyl transferase (MGMT) methylation status are all important in guiding optimal treatment, these should continue to be routinely determined.[1]


  Neuroimaging Top


As magnetic resonance imaging and computerized axial tomography are critical for the diagnosis of gliomas and monitoring the effects of therapy, they should continue to be performed. However, consideration may be given to increasing the interval between scans to reduce the frequency of visits to the hospital.


  Radiation Therapy Top


Standard radiation therapy for gliomas is usually approximately 5040 cGy for Grade II gliomas and 6000 cGy for high-grade gliomas (grade III and IV gliomas). These standard fractionation schedules require patients to come to the hospital for multiple visits and come in close contact with hospital staff, potentially increasing their risk of becoming infected by SARS-CoV-2. In addition, the on-site staffing required can strain the resources of hospitals. As a result, there is a significant interest in considering hypofractionation schedules to reduce the number of hospital visits.

In the elderly population of patients with glioblastoma (age >60 years), Roa et al.[6] showed that 60 Gy in 30 fractions over 6 weeks was equivalent to 40 Gy over 3 weeks. 34.0 Gy administered in 3.4 Gy fractions over 2 weeks also appears to be equally efficacious.[7] More recently, Roa et al.[8] compared the commonly used 3-week hypofractionation schedule (40 Gy in 15 daily fractions) with a short course of radiation therapy (25 Gy in 5 daily fractions over 1 week) in elderly patients with good performance status, elderly and frail patients and frail patients above the age of 50 years, and found no difference in survival or quality of life between the two regimens.

Tabrizi et al.[9] recently extracted individual patient-level data for 1321 patients from Kaplan–Meier curves from five randomized trials on the treatment of elderly glioblastoma patients including available subanalyses based on MGMT methylation status. They simulated trial data with incorporation of COVID-19-associated mortality risk in several scenarios (low, medium, and high infection, and mortality risks). Median overall survival and hazard ratios were calculated for each simulation replicate. They found that hypofractionated radiation therapy with concurrent and adjuvant temozolomide[10] demonstrated the best outcomes in low- and medium-risk scenarios. In frail elderly patients, shorter courses of radiation therapy were preferable.[9]

For patients below the age of 65 years and preserved functional status, standard radiation therapy fractionation schedules (60 Gy over 6 weeks for high-grade gliomas and glioblastomas) should be employed unless there are special constraints on resources.


  Chemotherapy Top


Standard therapy for gliomas involves the combination of radiation therapy with chemotherapy.[11],[12],[13] For low-grade gliomas and anaplastic astrocytomas, the regimen usually includes radiation therapy with procarbazine, lomustine (CCNU), and vincristine or temozolomide chemotherapy.[11],[13] If procarbazine, lomustine (CCNU), and vincristine is pursued, consideration should be given to omitting the vincristine given the likelihood that it contributes little to the benefit of the regimen as it does not cross the blood–brain barrier to any significant extent.[14] In patients with astrocytomas with intact 1p/19q (anaplastic astrocytomas), temozolomide should be administered only to patients with IDH mutations and methylated MGMT. Concomitant temozolomide should be omitted and only adjuvant temozolomide administered.[11]

In glioblastoma patients, radiation therapy with concomitant and adjuvant temozolomide is the standard of care.[12] Although this regimen is administered frequently to patients with unmethylated MGMT promoter, the benefit is negligible[15],[16],[17] and consideration should be given to omitting temozolomide in this population to reduce the risk of immunosuppression.

In elderly patients, there are data suggesting that temozolomide may be equally efficacious as radiation therapy in patients with MGMT-methylated glioblastomas.[7],[18] While the use of temozolomide alone may be reasonable in this patient population under normal circumstances, during the COVID-19 pandemic, it may be preferable to avoid chemotherapy and the resultant immunosuppression and consider radiation therapy instead, unless this is not readily available.[1] As in younger patients, consideration should be given to omitting temozolomide in elderly glioblastoma patients with unmethylated MGMT promoter.[7]

In patients with recurrent tumors, immunosuppressive alkylating agents should be avoided, if possible, and less immunosuppressive therapies such as bevacizumab and possibly regorafenib should be considered. If chemotherapy such as temozolomide or lomustine must be administered, it should be restricted to patients with tumors with MGMT promoter methylation.


  Tumor Treating Fields Top


Tumor treating fields have been shown by the EF-14 trial to potentially extend survival when administered with adjuvant temozolomide newly-diagnosed glioblastomas[19] and have received regulatory approval in a number of countries. Since this treatment does not produce immunosuppression and there are strategies to reduce potential infection by minimizing or completely avoiding contact with the technicians that usually provide support to the patients, it is reasonable to continue standard practice with this therapy.


  Clinical Trials Top


While there is a crucial need for clinical trials to improve the outcomes for glioma patients, the COVID-19 pandemic has serious affected many centers' ability to conduct these studies. In some centers, all clinical trials have been halted temporarily, while at other centers, laboratory support has been significantly curtailed, reducing the ability to conduct trials requiring extensive correlative studies. The reduction in in person visits has resulted in increasing the use of telemedicine to monitor the patients. In general, the transition to telemedicine has been successful. Hopefully after the pandemic there will be greater use of telemedicine in clinical trials, reducing the number of in person visits to the hospital by patients and enabling patients at greater distance to participate.


  Summary Top


The COVID-19 pandemic has irreversibly changed our world and the delivery of healthcare. The challenge is to continue to provide glioma patients with the best possible care during this difficult period. The pandemic has also made us reassess the care that we deliver and identify those aspects that are crucial and other practices that may have been routinely performed but are not critical. Hopefully, we will learn from this crisis and emerge from it with more efficient and effective strategies for managing glioma patients.



 
  References Top

1.
Bernhardt D, Wick W, Weiss SE, Sahgal A, Lo SS, Suh JH, et al. Neuro-oncology management during the COVID-19 pandemic with a focus on WHO Grade III and IV Gliomas. Neuro Oncol 2020. doi:10.1093/neuonc/noaa113.  Back to cited text no. 1
    
2.
Mohile NA, Blakeley JO, Gatson NT, Hottinger AF, Lassman AB, Ney DE, et al. Urgent considerations for the neuro-oncologic treatment of patients with gliomas during the COVID-19 Pandemic. Neuro Oncol 2020. doi:10.1093/neuonc/noaa090.  Back to cited text no. 2
    
3.
Chongsathidkiet P, Jackson C, Koyama S, Loebel F, Cui X, Farber SH, et al. Sequestration of T cells in bone marrow in the setting of glioblastoma and other intracranial tumors. Nat Med 2018;24:1459-68.  Back to cited text no. 3
    
4.
Minniti G, Lombardi G, Paolini S. Glioblastoma in elderly patients: Current management and future perspectives. Cancers (Basel) 2019;11:336.  Back to cited text no. 4
    
5.
Amin-Hanjani S, Bambakidis NC, Barker FG, Carter BS, Cockroft KM, Du R, et al. Editorial. COVID-19 and neurosurgical practice: An interim report. J Neurosurg 2020. doi:10.3171/2020.4.JNS201099.  Back to cited text no. 5
    
6.
Roa W, Brasher PM, Bauman G, Anthes M, Bruera E, Chan A, et al. Abbreviated course of radiation therapy in older patients with glioblastoma multiforme: A prospective randomized clinical trial. J Clin Oncol 2004;22:1583-8.  Back to cited text no. 6
    
7.
Malmström A, Grønberg BH, Marosi C, Stupp R, Frappaz D, Schultz H, et al. Temozolomide versus standard 6-week radiotherapy versus hypofractionated radiotherapy in patients older than 60 years with glioblastoma: The Nordic randomised, phase 3 trial. Lancet Oncol 2012;13:916-26.  Back to cited text no. 7
    
8.
Roa W, Kepka L, Kumar N, Sinaika V, Matiello J, Lomidze D, et al. International atomic energy agency randomized phase III study of radiation therapy in elderly and/or frail patients with newly diagnosed glioblastoma multiforme. J Clin Oncol 2015;33:4145-50.  Back to cited text no. 8
    
9.
Tabrizi S, Trippa L, Cagney D, Tanguturi S, Ventz S, Fell G, et al. A quantitative framework for modeling COVID-19 risk during adjuvant therapy using published randomized trials of glioblastoma in the elderly. Neuro Oncol2020. doi:10.1093/neuonc/noaa111.  Back to cited text no. 9
    
10.
Perry JR, Laperriere N, O'Callaghan CJ, Brandes AA, Menten J, Phillips C, et al. Short-course radiation plus temozolomide in elderly patients with glioblastoma. N Engl J Med 2017;376:1027-37.  Back to cited text no. 10
    
11.
van den Bent MJ, Baumert B, Erridge SC, Vogelbaum MA, Nowak AK, Sanson M, et al. Interim results from the CATNON trial (EORTC study 26053-22054) of treatment with concurrent and adjuvant temozolomide for 1p/19q non-co-deleted anaplastic glioma: A phase 3, randomised, open-label intergroup study. Lancet 2017;390:1645-53.  Back to cited text no. 11
    
12.
Stupp R, Mason WP, van den Bent MJ, Weller M, Fisher B, Taphoorn MJ, et al. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med 2005;352:987-96.  Back to cited text no. 12
    
13.
Buckner JC, Shaw EG, Pugh SL, Chakravarti A, Gilbert MR, Barger GR, et al. Radiation plus procarbazine, CCNU, and vincristine in low-grade glioma. N Engl J Med 2016;374:1344-55.  Back to cited text no. 13
    
14.
Boyle FM, Eller SL, Grossman SA. Penetration of intra-arterially administered vincristine in experimental brain tumor. Neuro Oncol 2004;6:300-5.  Back to cited text no. 14
    
15.
Stupp R, Mayer M, Kann R, Weder W, Zouhair A, Betticher DC, et al. Neoadjuvant chemotherapy and radiotherapy followed by surgery in selected patients with stage IIIB non-small-cell lung cancer: A multicentre phase II trial. Lancet Oncol 2009;10:785-93.  Back to cited text no. 15
    
16.
Hegi ME, Diserens AC, Gorlia T, Hamou MF, de Tribolet N, Weller M, et al. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med 2005;352:997-1003.  Back to cited text no. 16
    
17.
Hegi ME, Stupp R. Withholding temozolomide in glioblastoma patients with unmethylated MGMT promoter-still a dilemma? Neu ro Oncol 2015;17:1425-7.  Back to cited text no. 17
    
18.
Wick W, Platten M, Meisner C, Felsberg J, Tabatabai G, Simon M, et al. Temozolomide chemotherapy alone versus radiotherapy alone for malignant astrocytoma in the elderly: The NOA-08 Randomised, phase 3 trial. Lancet Oncol 2012;13:707-15.  Back to cited text no. 18
    
19.
Stupp R, Taillibert S, Kanner A, Read W, Steinberg D, Lhermitte B, et al. Effect of tumor-treating fields plus maintenance temozolomide vs. maintenance temozolomide alone on survival in patients with glioblastoma: A randomized clinical trial. JAMA 2017;318:2306-16.  Back to cited text no. 19
    



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Introduction
General Consider...
Surgery
Pathologic and M...
Neuroimaging
Radiation Therapy
Chemotherapy
Tumor Treating F...
Clinical Trials
Summary
References

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