|Year : 2020 | Volume
| Issue : 5 | Page : 49-53
Coronavirus disease 2019 pandemic and its implications on triaging patients with brain tumors for surgery, radiotherapy, and chemotherapy
Rakesh Jalali1, Jayant S Goda2, Vijay Patil3
1 Apollo Proton Cancer Centre, Chennai, Tamil Nadu, India
2 Department of Radiation Oncology (Neuro-Oncology Disease Management Group), Tata Memorial Centre, Mumbai, Maharashtra, India
3 Department of Medical Oncology (Neuro-Oncology Disease Management Group), Tata Memorial Centre, Mumbai, Maharashtra, India
|Date of Submission||04-Apr-2020|
|Date of Decision||06-Apr-2020|
|Date of Acceptance||06-Apr-2020|
|Date of Web Publication||25-Apr-2020|
Apollo Proton Cancer Centre, 100 Feet Road, Taramani, Chennai - 600 041, Tamil Nadu
Source of Support: None, Conflict of Interest: None
The coronavirus disease 2019 pandemic has the potential to overwhelm the current health-care system in our country. The oncologists face a tricky question as to whom to prioritize treatment for. Postponing cancer treatments might be associated with some risk of compromised clinical outcomes. The risks need to be considered in light of the magnitude of potential benefits, the impact of delaying standard treatment on outcomes, and competing patient-centric and infrastructure priorities. Treatment decisions during the pandemic have to be triaged and prioritized based on the existing health-care facility and the fluidity of the situation. High-priority and urgent interventions include management of suspected high-grade glioma, primary central nervous system lymphoma, and round cell tumors. Low-priority interventions include management of low-grade glioma, benign tumors, and relapsed-refractory brain tumors. Similar to other cancers, the management of patients with brain tumors also needs to be adapted and prioritized; pragmatic patient treatment pathways need to be formalized without compromising the clinical outcomes and overburdening the health infrastructure. Health-care professionals dedicated to oversee the management of patients with brain tumors may have to triage referrals and modify the management of various brain tumors, as treatment pathways will differ from region to region and country to country based on the ground level situation. This document is an endeavor to provide a basic framework to triage and prioritize brain tumor patient management pathways. As the situation is rapidly evolving, we suggest a basic treatment guideline for these patients, which is simple to adopt.
Keywords: Brain tumor, coronavirus disease 2019, neuro-oncology, SARS, SARS-CoV-2, COVID-19, India, LMIC
|How to cite this article:|
Jalali R, Goda JS, Patil V. Coronavirus disease 2019 pandemic and its implications on triaging patients with brain tumors for surgery, radiotherapy, and chemotherapy. Cancer Res Stat Treat 2020;3, Suppl S1:49-53
|How to cite this URL:|
Jalali R, Goda JS, Patil V. Coronavirus disease 2019 pandemic and its implications on triaging patients with brain tumors for surgery, radiotherapy, and chemotherapy. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Jul 7];3, Suppl S1:49-53. Available from: http://www.crstonline.com/text.asp?2020/3/5/49/283288
| Introduction|| |
At the time of writing this article, the number of patients afflicted with coronavirus disease 2019 (COVID-19) due to the virus strain, severe acute respiratory syndrome (SARS) coronavirus 2, around the world has reached one million, and India has thousands of active cases. Given the infectivity of this virus, the spread will likely become exponential in the coming weeks, resulting in a large number of patients being severely affected, requiring hospital and intensive care unit (ICU) admission and ventilatory support.
India being the second most populous country in the world is still in Stage-II (confined to local transmission only), but a rapid increase in the number of infected individuals and the relatively challenged health-care infrastructure may disrupt the health-care delivery. These disruptions may not be limited to SARS-infected patients alone, but also to patients with other comorbidities who may require treatment for their condition as per standard management guidelines, taking into consideration our health-care limitations and the safety issues of health-care providers and caregivers of the patients.
At present, the data point out that older people, patients with certain comorbidities such as diabetes and hypertension, and patients with cancer who are immunocompromised may develop severe infections requiring hospitalization and active treatment., The data on the impact of COVID-19 infection on patients with cancer and its morbidity/mortality are not fully known.
Similarly, data on patients with brain tumors in the setting of the COVID-19 pandemic are limited.,, It is difficult to run regular services due to shortage of medical staff, operation theaters, and ICUs and potential shortage of personal protective equipment (PPE) and blood and blood products. Health-care professionals dedicated to oversee brain tumor patient management need to adapt to the ongoing situation, prioritize the treatment approach, triage referrals, and optimize treatment protocols as judiciously as possible. The present document provides a pragmatic framework for implementing management protocols for brain tumor patients under the present conditions in India.
| Triaging patients even before the outpatient clinic consultations|| |
- Screen out patients with suspected COVID-19 symptoms. A good practice would be to have a makeshift screening clinic at or outside the hospital entrance where patients can be screened even before actual consultation
- Use non face-to-face consultation where possible and minimize hospital visits
- Try to defer visits of asymptomatic or mildly symptomatic patients in the outpatient clinic if there is either a pathological and/or radiological diagnosis of a benign brain tumor like a pituitary adenoma, meningioma schwannomas, and pediatric and adult low-grade gliomas.
| Outpatient clinics for new patients with brain tumors|| |
- See only referrals when there is a magnetic resonance imaging (MRI) or an established pathological diagnosis of a brain tumor
- Discourage face-to-face contact with patients except for those with malignant brain tumors such as high-grade gliomas, primary central nervous system (CNS) lymphomas, or patients who would require urgent surgical intervention or early adjuvant therapy with radiotherapy (RT) and/or chemotherapy
- A good practice is to use PPE like N95-N97 face mask when evaluating the patient and the attendants if the risk is high. There is a high risk if the patient has a travel history, a history of contact with COVID-19 patients, or is coming from a COVID-19 hotspot area
- If the risk is minimal, maintain a safe distance (>1meter) and wear a triple-layered mask
- Try to keep the discussion to a minimum during the consultation.
| OUTPATIENT CLINICS FOR FOLLOW-UP BRAIN TUMOR PATIENTS AND THE IMPORTANCE OF TELEPHONIC/VIDEO CONSULT|| |
- Call the patients to follow-up clinic only when necessary
- That is, when the patient is symptomatic (moderate-to-severe headache, hemiplegia, incessant vomiting, and seizures) or when the clinician suspects disease relapse or progression.
- Call the patient to the outpatient clinic with an MRI so as to reduce the time of contact with the patient
- Defer routine patient follow-up in the clinic
- Routine clinical follow-up which does not require review of imaging should be managed by either telephonic or video consult
- Continue to support all patients, even those who may now not get treatment through telephonic consult.
Teleconsulting and video consults should be encouraged between treating physicians and patients, as already demonstrated by the results of the Tata Memorial Hospital (Mumbai, India) Shadow study, which found a high level of agreement on treatment decisions between the virtual and clinical follow-up.
| Multidisciplinary brain tumor clinics|| |
- Every single brain tumor case does not need to be discussed in the multidisciplinary tumor (MDT) board
- Encourage virtual MDT boards, preferably via virtual methods to triage patients for surgery, RT, and chemotherapy for those most likely to benefit
- Maintain MDT but reduce attendance to key decision-makers only
- Virtual MDT among key decision-makers should be encouraged rather than having physical meetings.
| Surgery for patients with brain tumors|| |
Patients with high surgical priority
- Reduce impact on the inpatient resources by having short-stay overnight surgery for all procedures with no or minimal admission to critical care
- Reserve surgery for urgent cases, such as patients who have decompensated hydrocephalus and require measures such as emergency shunt placement extraventricular drain placement and patients who are at risk of coning down
- Posterior fossa tumors causing life-threatening hydrocephalus
- Supratentorial symptomatic brain metastases
- Germ cell tumors and pineoblastoma where tissue diagnosis is important since therapy needs to be initiated early.
- Consider non-operative approaches in patients least likely to gain significant benefit from treatment, e.g., older patients with poor performance status with clear features of high-grade glioma (glioblastoma multiforme [GBM]) on MRI (e.g., best supportive care)
- Postoperatively, try to minimize the hospital stay as much as possible (if possible, discharge the patient in a day or two); avoid transsphenoidal/transoral routes where aerosol contamination is highest. Involve minimal assistants. Guidelines for safe donning and doffing of PPE are to be strictly followed
- For malignant gliomas, resect tumors of only those patients who are suitable for adjuvant treatment.
Patients with low surgical priority
- Defer elective surgeries as much as possible
- Low-grade glioma where a period of interval monitoring with MRI is a reasonable option (a delay of 3–6 months can be considered). In such situations, an interval MRI can be done to ensure there is no tumor progression)
- Benign tumors (e.g., meningioma, vestibular schwannoma, pituitary adenomas, and craniopharyngiomas) with minimal symptoms can be deferred for surgery
- Brain metastasis, as alternative therapy in the form of stereotactic radiosurgery, is available.
| Radiation therapy for brain tumor patients|| |
High-priority patients: Patients in whom early initiation of radiotherapy should be considered
- For malignant gliomas like GBM
- Older patients (>60 years, Karnofsky performance status [KPS] between 60 and 70): Hypofractionated RT dose of 35 Gy/10 fractions or 40 Gy/15 fractions with temozolomide
- Older patients (age >60 years, KPS <60): 35 Gy/7 fractions weekly or 25 Gy in 5 fractions without temozolomide
- Younger patients (<60 years, KPS >70): 60 Gy/30 fractions with concurrent temozolomide
- Younger patients (<60 years, KPS <70): Hypofractionation; 40 Gy/15 fractions with concurrent temozolomide.
- RT for other malignant tumors (e.g., anaplastic astrocytoma, pineoblastoma, primitive neuroectodermal tumor [PNET], medulloblastoma, germ cell tumors)
- Anaplastic ependymoma patients should be given RT
- For brain metastasis, where palliation is the indication
- Whole-brain RT: RT dose 20 Gy/5 fractions or 12 Gy in 2 fractions 1 week apart.
- For oligo brain metastasis with controlled extracranial disease
- Stereotactic radiosurgery: high-dose single-fraction or extreme hypofractionation should be used.
- For patients with primary CNS lymphoma who are partial responders to high-dose methotrexate (MTX) or in patients who are not candidates for high-dose MTX
- Whole-brain RT dose of 20 Gy/5 fractions may be considered.
- RT techniques should be devised according to the institutional practice so that there is minimum exposure of the staff to the patient.
Low-priority patients: Consider deferring radiation therapy
- Defer radiation treatment for benign tumors and low-grade gliomas
- Grade I–II meningiomas, recurrent meningiomas, schwannomas, pituitary adenomas, and craniopharyngiomas.
- RT for low-grade glioma where an initial period of monitoring is a reasonable option such as molecularly favorable low-grade gliomas
- RT can be deferred for grade-II ependymoma.
| Chemotherapy for patients with brain tumors|| |
High-priority patients: Patients in whom chemotherapy should be considered
- Glioblastoma patients who are isocitrate dehydrogenase (IDH) mutant, O6-methylguanine-DNA methyltransferase (MGMT) methylated should be given both concurrent and maintenance. temozolomide. Consideration can be given to restrict the number of cycles of adjuvant therapy to six cycles. In the relapsed-recurrent setting, single-agent bevacizumab should be preferred
- Anaplastic astrocytomas, IDH mutant, should be given both concurrent and maintenance temozolomide
- Recurrent high-grade gliomas
- Primary CNS lymphomas where high-dose MTX is the most active agent along with rituximab. Rituximab causes prolonged immunosuppression and needs to be avoided in high-risk patients
- Evaluate for risk factors such as advanced age, diabetes, and hypertension
- High risk: Give MTX but omit dexamethasone and rituximab. If KPS is 60–70, then consider single-agent temozolomide. The regimen may be converted to a MTX-based regimen if the KPS improves
- Low risk (absence of the above factors): Give MTX, dexamethasone, and rituximab. Consider starting rituximab after 1–2 cycles.
- For PNETs, medulloblastoma, pineoblastoma, and germ cell tumors, adjuvant chemotherapy should not be deferred. Consideration should be given to administer granulocyte colony-stimulating factor prophylaxis to reduce the impact of immunosuppression. For medulloblastoma, lomustine (CCNU)-containing regimens preferably should be avoided
- In brain metastasis: Preferably a targeted agent, if applicable, should be used. For example, osimertinib in sensitive-epidermal growth factor receptor-mutated lung cancer, alectinib in ALK-rearranged lung cancer, trastuzumab in HER2/neu-amplified breast cancer, etc. In case of absence of the target, the decision regarding administration of chemotherapy should be based on extracranial considerations. If extracranial disease requires chemotherapy, it should be offered, and if not, chemotherapy should be restricted.
Low-priority patients: Consider deferring chemotherapy
- Chemotherapy may be omitted in MGMT-unmethylated glioblastoma patients and IDH-mutation negative anaplastic astrocytoma
- In oligodendrogliomas including Grade-III, temozolomide should be preferred over procarbazine, lomustine, and vincristine (PCV) regimen
- (Aggressive) Low-grade gliomas.
| Best supportive care|| |
- Older patients with GBM (age >60 years, non-ambulatory, KPS: 40–50)
- Older patients of primary CNS lymphoma with poor KPS and not candidates for high-dose MTX, palliative RT, or even oral chemotherapy.
| Emergency ancillary treatment|| |
- In case of intracranial bleed and the patient is deteriorating: Evacuation of the bleed should be considered or else can be observed with interval scans
- In case of raised intracranial tension: Medical decompressive therapy should be considered after due consideration for high-risk factors such as advanced age, diabetes, or hypertension
- If high risk for COVID: Omit dexamethasone and give intravenous mannitol only after admission with due COVID precautions
- If low risk, give mannitol and tapering doses of dexamethasone
- In case of seizures: Start on oral antiepileptics (oral levetiracetam).
- In case of intractable seizure that may be life-threatening: Patient will require admission with all the COVID precautions and administration of intravenous antiepileptics (loading dose of phenytoin followed by intravenous levetiracetam)
- In case of seizures in COVID-diagnosed patients: Neurological symptoms due to COVID-19 should be considered. The rare possibility of acute necrotizing encephalopathy related to COVID-19 needs to be considered
- The Indian Council of Medical Research (ICMR) has recommended hydroxychloroquine in high-risk patients. An interaction check should be performed when prescribing any medication.
| MANAGEMENT OF PATIENTS IN CLINICAL TRIALS DURING CORONAVIRUS DISEASE 2019|| |
- New patients should not be enrolled in a clinical trial as the circumstances are unusual and changing
- Patients already enrolled in clinical trials and already under active treatment can be continued in the trial under proper medical supervision.
- Trials questioning the role of RT (RT dose and RT technique) in brain tumors can be continued
- Trials involving chemotherapy drugs such as CCNU, PCV or any other drugs that are known to cause immunosuppression should be withheld till the COVID-19 infection is brought under control
- Trials involving patient reported outcomes may be continued. Investigators should follow their institutional review board guidelines as formulated in the current situation.
| TRIAGING PATIENTS WITH BRAIN TUMORS DURING CORONAVIRUS DISEASE 2019 PANDEMIC|| |
A flow diagram of triaging patients with brain tumor during the COVID outbreak in India is shown in [Figure 1].
|Figure 1: A flow diagram of triaging patients with brain tumor during the COVID-19 outbreak in India. COVID-19: Coronavirus disease 2019; MRI: Magnetic resonance imaging; MDT: Multidisciplinary tumor board; GBM: Glioblastoma; PPE: Personal protective equipment; CNS: Central nervous system; PCNSL: Primary CNS lymphoma, KPS: Karnofsky performance status; RT: Radiotherapy|
Click here to view
| Conclusion|| |
This emergency situation calls for prioritizing decision-making processes based on the individual patient, institution, tumor risk assessments, and the overall situation prevailing in the region and in the country. Based on the risk assessments, the patient and the caregivers need to be informed of the situation and the need to alter the treatment policies and the possible long-term impact on the clinical outcomes. Last but not the least, institutional policies for treating brain tumor patients should be driven by careful weighing of all the available information and in particular the long-term benefit of the given treatment.
The guideline document is a work in evolution and depending on the enormity of the COVID-19 situation in our country, there is a possibility of updating these guidelines.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Zhou F, Yu T, Du R, Fan G, Liu Y, Liu Z, et al
. Clinical course and risk factors for mortality of adult inpatients with COVID-19 in Wuhan, China: A retrospective cohort study. Lancet 2020;395:1054-62.
Bansal N, Ghafur A. COVID-19 in oncology settings. Cancer Res Stat Treat 2020;3:13-4. [Full text]
Liang W, Guan W, Chen R, Wang W, Li J, Xu K, et al
. Cancer patients in SARS-CoV-2 infection: A nationwide analysis in China. Lancet Oncol 2020;21:335-7.
van den Bent MJ. COVID-19 and neuro-oncology: Considerations for daily care of brain tumour patients. Available from: https://www.eano.eu
. [Last accessed on 2020 Apr 03].
Patil VM, Pande N, Chandrasekharan A, Chandrakanth M, Tonse R, Krishnatry R, et al
. Shadow study: Randomized comparison of clinic with video follow-up in glioma undergoing adjuvant temozolomide therapy. CNS Oncol 2018;7:CNS14.