Management of Glioblastoma Multiforme as a Big Challenge for Neurosurgeons and Radiation Oncologists in Covid-19 Era: An Institutional Experience in a Rural Sub-Himlayan Region

Objectives: To illustrate our institutional experience about the challenges we faced and steps taken in the management of the patients with Glioblastoma multiforme during Covid 19 crises at Dr. R.P.G.MC Tanda. Methods: In the period of complete lockdown, patients were treated surgically without much delay. Patients with incomplete resection were given radiation while the ones with complete resection were started on tablet temozolamide (TMZ) alone and were sent home after counselling. At the period of partial lockdown patients below 70 years were given option of starting on hypofractionated radiation or tab temozolamide, 55% of the patients preferred radiation over temozolamide while rest continued on tablet temozolamide. Further, the patients above 70 years were continued on tablet temozolamide and were kept on telephonic check for the onset of any neurological symptoms, those developing symptoms were immediately called and started on short course radiotherapy to a dose of 40GY/15#/3 weeks or 34GY/10#/1 weeks or 25GY/5#/1 week or were treated by Stereotactic radiotherapy 8GY/5# by Volumetric Arc Radiotherapy. Results: In our institute all of our GBM patients below 70 years remained asymptomatic when started on the non standard treatmenton tab temozolamide only post surgery or on hypofractionated course of radiotherapy and only 2% patients above 70 years developed slight symptoms showed progression of disease on check MRI scan were given hypofractionated radiotherapy. Conclusion: Covid 19 pandemic has resulted in unprecedented global healthcare crises. Our institution has illustrated the challenges we faced in managing patients with highly dreadful Glioblastoma multiforme. Due to the fear of increased risk of Covid 19 infection in the cancer patients which would result in devastating complications and very poor outcome, the non standard strategy of keeping the patients on tab temozolamide only post surgery or on hypofractionated course of radiotherapy resulted in symptomatic relief in patients below 70 years of age and only 2% patients above 70 years who developed slight symptoms showed progression of disease on check MRI scan. . Though, not standard this strategy can be considered in covid-19 crises.


Introduction
On March 11,2020 Coronavirus disease (Covid-19) was declared as global pandemic by the World health organization [1]. This has resulted in unprecedented challenges and changes in healthcare delivery everywhere so as to reduce exposure to virus and transmission. The brain tumours like Glioblastoma Multiforme (GBM) deserves special attention due to it's presentation in older age and being more vulnerable

Why is counselling GBM patient his Relatives so challenging?
As cancer is taken as stigma in the society, and when patient is diagnosed with brain tumour that too with the most aggressive and lethal tumour he and his relativesbecome helpless and hopeless. Moreover, in the period of such pandemic when he needs immediate treatment and everything gets shut down even hospital which remains the last hope for him, he becomes completely broken with continuous fear of disease progression and death. Counselling them at this point of time is also very challenging Why is management of GBM so challenging to the neurosurgeons in this pandemic?
As GBM is the disease of old age and patients usually have co-morbidities which is itself challenging.
Owing to the exponential increase in the number of cases with very high infectivity rate, most of the neurosurgeons had stopped elective interventions in some benign brain tumours, but GBM is a very aggressive tumour with very high proliferative rate and postponement of surgery in any circumstances is not at al justifi able.

Why is management of GBM so challenging to the radiation oncologists in this Pandemic?
Post-operative radiotherapy is indispensable for GBM with clear cut survival benefi t in randomized studies [2]. For what time radiotherapy can be postponed after surgery?
Ideally Radiation (RT) should not be postponed, it should be given as per guidelines, ASCO guidelines states that RT should be initiated as soon as safely permissible; some trials have started RT within 3-6 weeks of surgery.
One study on 172 patients showed that the addition of every one week (after 2 weeks of surgery) increases the risk of death by 8.9% [3], while another study on 179 patients of malignant glioma showed no effect of waiting time between surgery and radiotherapy on survival [4].
The delay in initiating radiotherapy in GBM leads to detriment in overall survival was shown in three case series [3][4][5]. In contrast to this there was no reduction in survival with delayed radiation by 6 weeks after diagnosis on analysis of 2855 patients in 16 Radiation Therapy Oncology Group (RTOG) studies [6].

Why Should we consider Hypofractionated radiotherapy in this Pandemic?
Hypofractionated Radiotherapy (HFRT) gets completed early, and thereby, reduces burden on medical resources, patient himself and his relatives [7].
Evidence says that in older patients (>60 years or more) there is no difference in median survival between HFRT and standard course radiotherapy [7][8][9] and had better survival in temozolomide with the omission of RT, and each regimen was supported by prospective trial data [7,8].

Protocol Followed at out institute at the period of Covid-19
In the period of complete lockdown, patients were treated Steps taken in our institute to decrease rush in the outpatient care are given in Table 1.

Precautions taken in the Radiation Zone by our Institute
To

Conclusion
The present situation forced us to modify our treatment plans by using hypofractionated radiotherapy or temozolamide to minimize the risk of exposure and transmission. We should try our best to provide best possible treatment.  Steps taken in our institute to decrease rush in the outpatient care.

Purpose Measures
Reducing the risk of patients exposure The visits were restricted to the patients on active treatment /requiring urgent attention. All the routine follow-ups were postponed and teleconsultation was started. All unnecessary interventions like routine imaging, blood tests, serum markers in asymptomatic patients were postponed limiting the number of patients in waiting area posters pasted in waiting area regarding social distancing Reducing the exposure to the staff Only patients were allowed inside the OPDs. Only one attendant (uninfected) was allowed to accompany the patient outside OPDs. To minimize the exposure to the staff, roster was made in which healthcare workers and physicians were not called daily and were assigned specifi c duty days Reducing the number of medical staff Reducing the number of nursing staff. Reducing the number of staff at reception. All the staff to wear gowns, masks and gloves