Abstract
Introduction
The COVID19 pandemic had a strong impact on the healthcare system, particularly in oncology. Brain tumor are usually revealed by acute and life threatening symptoms. We wanted to evaluate the possible consequences of the COVID19 pandemic in 2020 on the activity of neuro-oncology multidisciplinary tumor board in a Normandy region (France).
Methods
A descriptive, retrospective, multicenter study was conducted in the four referent centers (two universitary hospitals and two cancer centers). The main objective was to compare the average number of neuro-oncology patients presented per multidisciplinary tumor board per week between a pre-COVID19 reference period (period 1 from December 2018 to December 2019) and the pre-vaccination period (period 2 from December 2019 to November 2020).
Results
Across Normandy, 1540 cases were presented in neuro-oncology multidisciplinary tumor board in 2019 and 2020. No difference was observed between period 1 and 2: respectively 9.8 per week versus 10.7, P = 0.36. The number of cases per week also did not significantly differ during the lockdown periods: 9.1/week versus 10.4 during the non-lockdown periods, P = 0.26. The only difference observed was a higher proportion of tumor resection during the lockdown periods: 81.4% (n = 79/174) versus 64.5% (n = 408/1366), P = 0.001.
Conclusion
The pre-vaccination era of the COVID19 pandemic did not impact the activity of neuro-oncology multidisciplinary tumor board in the Normandy region. The possible consequences in terms of public health (excess mortality) due to this tumor location should now be investigated.
Keywords: Primary brain tumor, Neuro-oncology, COVID 19, Sars-Cov2, Multidisciplinary tumor board
Abbreviations
- COVID19
Coronavirus-disease 2019
- MDT
Multidisciplinary tumor board meeting
- MGMT
O6-Methylguanine DNA Methyltransferase
- TMZ
temozolomide
- RT
radiotherapy
1. Introduction
The coronavirus disease 2019 (COVID19) pandemic resulted in a significant disruption of the healthcare system worldwide specially during the pre-vaccine era. Lockdown, health distancing measures as well as the reorganization of hospital care supply particularly impacted the standard of care of non-COVID patients. Among them, the specific impact on patients suffering from cancer was significant due to potential delay in diagnosis and treatment [1]; and to recommendations for the isolation of cancer patients deemed to be at risk of severe forms [2]. This impact is particularly true for cancers covered by national screening programs screened and/or not symptomatic cancers in the initial phase, such as breast or colorectal cancers.
There is probably heterogeneity in access to diagnosis depending on the initial symptoms. With around 5500 to 6000 new cases per year in France [3], primary brain tumors are revealed by acute symptoms such as seizure, intracranial hypertension and neurological deficit. The initial clinical presentation usually requires rapid management in reference centers as university hospitals and cancer centers. Several guidelines in neuro-oncology adapted to the COVID19 pandemic were published back in 2020 [4], [5]. For example, guidelines recommended to maintain tumor resection in selected situation such as malignant tumor in young and/or fit patients.
Tumor resection is known to be crucial for histomolecular diagnosis [6] and for prognosis in common malignant tumor such as high-grade glioma [7]. Tumor molecular characterization is also required for adjuvant treatment decision, for example MGMT promoter methylation for elderly patients [8] or IDH mutant glioma [9].
The impact on neurosurgical activity along the initial phase of the COVID19 pandemic is not clearly established [10], [11]. In this context, we conducted a descriptive study during the COVId19 pandemic on the activity in neuro-oncology in Normandy region (France) for BRAIN tumor diagnosis: COVIBRAIN study. The main objective was to compare the activity in neuro-oncology MultiDisciplinary Tumor board meeting (MDT) between the pre-COVID19 period and the initial phase of the COVID19 epidemic before the vaccination.
2. Patients and methods
2.1. Study design and data collection
COVIBRAIN study was an observational, retrospective, and multicenter study. Four centers were included: two university hospitals (Charles Nicolle University Hospital at Rouen and Côte de Nacre University Hospital at Caen) and two cancer centers (Henri Becquerel at Rouen and François Baclesse at Caen). Data were collected from institutional database between December 2018 and December 2020. Patients were selected using the centralized neuro-oncology MDT. All adult patients (i.e. 18 years of age or older) suffering from suspected and/or histologically confirmed primary brain tumor were included. Patients suffering from brain metastases were not included. For each presented case at the MDT the following data were collected: patient demographics (sex, age), initial or follow-up management, details on surgery procedure (biopsy or surgery), non-surgical therapeutic recommendations (radiochemotherapy, chemotherapy alone, radiotherapy alone, best supportive care, follow-up). Newly-diagnosed primary brain tumors along the studied period were collected using neuropathology data files. Non-surgical treatments were also collected: chemotherapy (molecule, number of administration) and radiotherapy. The regional incidence of SARS-CoV-2, the number of hospitalized patients in intensive care and the total number of hospitalizations due to this infection were obtained from the French national database.
2.2. Objectives
The main objective of COVIBRAIN study was to compare the number of patients presented at MDTs for a primary brain tumor from December 1st 2019 to November 30th 2020 (period 2) to a control period from December 1st 2018 to November 30th 2019 (period 1).
Secondary objectives were to compare: (i) the number of newly-diagnosed patients for a primary brain tumor based on neuropathology cases between the period 1 and period 2; (ii) the number of delivered treatments (chemotherapy and radiotherapy) between the above-mentionned periods.
We also conducted an exploratory analysis of the number of patients presented at MDTs between the two lockdown periods in France (from March 17th 2020 to May 11th 2020 and from October 30th 2020 to December 15th 2020) compared to the non-lockdown periods.
Finally, we investigated the association between the number of hospitalized patients due to Sars-Cov-2 infection and the number of cases presented in neuro-oncology MDT per week.
2.3. Statistical analysis
To meet the primary and secondary objectives, comparisons of proportions were performed with chi-square test or the exact Fisher test as appropriate. The alpha risk threshold was set at 5%. Figures and analyses were performed in RStudio version 1.2.1335 (RStudio, Inc.) using the ggpubr package.
3. Results
3.1. Multidisciplinary Tumor Board Meeting
During the period from December 2018 to November 2020, 1540 cases were discussed in MDT in the four included centers: 735 within the period 1 (non Covid period) and 805 within the period 2 (Covid period) (Table 1 ). No difference was observed between the two periods as regard to population characterisctics or tumor histology. As expected, glioma and malignant or refractory meningioma were the most represented tumors: respectively 73.3% (n = 1129/1540) and 13.2% (n = 204/1540) in the entire population. Mean number of cases per MDT per week was similar between the two periods: 9.8 in the period 1 and 10.7 in the period 2, P = 0.36 (Fig. 1a and Table 1).
Table 1.
Characteristics of the patients’ cases discussed during studied period — COVIBRAIN study (2019–2020). Data were collected between December 1st 2018 to November 30th 2019 (Period 1) and December 1st 2019 to November 30th 2020 (Period 2).
| Period 1 | Period 2 | P | |
|---|---|---|---|
| n | 735 | 805 | |
| Gender = men (%) | 388 (52.8) | 440 (54.7) | 0.494 |
| Age (mean (SD)) | 58.3 (15.79) | 59 (14.83) | 0.339 |
| Number of MDM per week (mean (SD)) | 9.8 (5.19) | 10.7 (4.99) | 0.36 |
| Type of MDM (%) | 0.44 | ||
| Initial | 286 (38.9) | 303 (37.6) | |
| Follow up | 437 (59.5) | 502 (62.4) | |
| Unknown | 12 (1.6) | 0 (0.0) | |
| Tumor resection (%) | 200 (64.1) | 287 (68.7) | 0.225 |
| Histology (%) | 0.193 | ||
| Astrocytic/oligodendroglial tumors | 528 (71.8) | 601 (74.7) | |
| Choroid plexus tumors | 2 (0.3) | 1 (0.1) | |
| Cranial nerves tumors | 5 (0.7) | 1 (0.1) | |
| Embryonal tumors | 8 (1.1) | 3 (0.4) | |
| Ependymal tumors | 12 (1.6) | 12 (1.5) | |
| Germ cell tumors | 1 (0.1) | 2 (0.2) | |
| Lymphomas | 18 (2.4) | 18 (2.2) | |
| Meningiomas | 102 (13.9) | 102 (12.7) | |
| Mesenchymal tumors | 7 (1.0) | 12 (1.5) | |
| Neuronal/glioneuronal tumors | 9 (1.2) | 4 (0.5) | |
| Other astrocytic tumors | 2 (0.3) | 4 (0.5) | |
| Other gliomas | 0 (0.0) | 3 (0.4) | |
| Other/unknown | 16 (2.2) | 9 (1.1) | |
| Sellar region | 25 (3.4) | 33 (4.1) |
Fig. 1.
Comparison of cases per week per MDT in Normandy between period 1 (December 1st 2018 to November 30th 2019) and period 2 (from December 1st 2019 to November 30th 2020) (a); between lockdown periods and non lockdown period (b); and per year. MDT: multidisciplinary tumor board meeting.
During the lockdown periods, 174 cases were presented and no difference in the number of cases per week was observed between lockdown and non-lockdown periods: respectively 9.1 cases/week versus 10.4, P = 0.26 (Fig. 1b).
The only observed difference was a higher proportion of tumor resection during the lockdown periods: 81.4% (n = 79/174) versus 64.5% (n = 408/1366), P = 0.001. When considering the calendar year, no difference was observed between 2019 and 2020 (Fig. 1c). Within the year 2020, the only significant decrease of number of MDT cases was observed in October, as compared to October 2019 (Fig. 2 ). This difference, although not significant, was observed when comparing the 2020 overall mean number of cases to the mean per month (Supplementary Fig. A). A slight and opposite correlation was observed (coefficient correlation = 0.17, P = 0.002) between the number of cases per week and the number of patients hospitalized for a Sars-Cov-2 infection (Fig. 3 ).
Fig. 2.
Comparison of cases presented at the neuro-oncology MDT in Normandy per month between 2019 and 2020.
Fig. 3.
Linear regression of the number of cases per week as a function of the concomitant number of hospitalized patients for a Sars-Cov-2 infection.
Regarding newly and histomolecular confirmed diagnosis (by resection or biopsy), no difference was observed between the two periods: 480 news cases during period 1 and 494 new cases during period 2. Repartition by histomolecular subtypes shows no significant difference (Fig. 4 ).
Fig. 4.
Repartition and comparison of histomolecular newly-diagnosed cases between period 1 and period 2 per tumor type.
3.2. Treatments decision
No difference in the MDT decision was observed between the period 1 and the period 2 (Table 2 ).
Table 2.
Comparison of the number of delivered treatments between the period 1 and the period 2 — COVIBRAIN study (2019–2020).
| Period 1 | Period 2 | P | |
|---|---|---|---|
| n | 735 | 805 | |
| Radiotherapy = yes (%) | 269 (36.6) | 291 (36.1) | 0.896 |
| Type of radiotherapy (%) | 0.414 | ||
| Protontherapy | 42 (15.6) | 44 (15.1) | |
| Short-course radiotherapy | 21 (7.8) | 18 (6.2) | |
| Standard-course radiotherapy | 190 (70.6) | 219 (75.3) | |
| Stereotactic radiotherapy | 16 (5.9) | 10 (3.4) | |
| Chemotherapy = yes (%) | 424 (57.7) | 470 (58.4) | 0.822 |
| Temozolomide | 222 (52.4) | 230 (48.9) | 0.435 |
| RT/TMZ + TMZ protocol | 149 (35.1) | 152 (32.3) | |
| TMZ monotherapy | 69 (16.3) | 74 (15.7) | |
| TMZ + anti-VEGF | 2 (0.5) | 4 (0.9) | |
| TMZ + topotecan | 2 (0.5) | 0 (0.0) | |
| Nitrosourea | 82 (19.3) | 90 (19.1) | 0.48 |
| Nitrosourea monotherapy | 35 (8.3) | 38 (8.1) | |
| Nitrosourea + anti-VEGF | 31 (7.3) | 40 (8.5) | |
| PCV regimen | 16 (3.8) | 12 (2.6) | |
| Anti-VEGF monotherapy | 51 (12.0) | 73 (15.5) | |
| Platine based regimen | 26 (6.1) | 26 (5.5) | 0.24 |
| Platine + anti-VEGF | 7 (1.7) | 11 (2.3) | |
| Platine monotherapy | 19 (4.5) | 15 (3.2) | |
| Other chemotherapy | 31 (7.3) | 30 (6.4) | |
| Targeted therapy | 1 (0.2) | 3 (0.6) | |
| Clinical trial | 5 (1.2) | 8 (1.7) |
About radiotherapy, we did not find any modification in proposed radiation-fraction or technique, P = 0.896. As an example, 21 patients had a short course radiotherapy during period 1 and 18 patients during period 2, P = 0.414.
Regarding chemotherapy treatments, no difference was observed between the two periods, P = 0.822. Interestingly, proposition for inclusion in clinical trials was continued due to the maintenance of clinical research in oncology.
Finally, we explored the impact of COVID19 on the volume of oncologic treatments for a primary brain tumor and administered during the two periods. The number of radiotherapy sessions in the two main centers in Normandy (François-Baclesse center and Henri-Becquerel center) did not change, nor has the quantity of chemotherapy delivered by the hospital pharmacy at the Henri-Becquerel center (Supplementary Fig. B).
4. Discussion
COVIBRAIN study showed that the COVID19 pandemic did not impact MDT activity in neuro-oncology in 2020 compared to 2019 in Normandy. Non-significant monthly variations were observed and appear to be related to the number of hospitalizations for Sars-Cov-2 infection. These results are the first described in France on the specific population of patients suffering from primary brain tumor.
The data presented are exhaustive on a French region representing 5% of the French metropolitan population. These results are in line with the similar comparative experience in a New York center: 133/166 patients (80%) were managed at their center from a primary brain tumor in 2020 versus 90/112 patients (80%) in 2019 [12]. However, the study conducted in 18 English centers showed a significant reduction in the number of cases presented in MDT per week between March 23 and April 20, 2020 versus February 2020 (baseline) with an average of 15.3 patients versus 21.2 respectively, P = 0.0005 [11]. This difference can be explained by the choice of the studied period. In COVIBRAIN study, we explored the overall annual impact of the pandemic on neuro-oncology activity. Our results showed possible monthly variation, but comparison was not possible due to lack of statistical power. It would be interesting to perform a national-based analysis of the number of cases presented per week while studying the correlation with the hospital pressure related to COVID19.
Regarding all tumor localizations in another Occitania region (France), Grosclaude et al. [13] observed a significant reduction of 23% in the number of cases presented at MDT when comparing 2019 and 2020; with a peak of decrease at 33% during the third week following the first lockdown. Our exploratory results did not find any significant impact of lockdown periods on the average number of cases presented in neuro-oncology MDT. The particularity of the tumor location with acute neurological deficit could partially explained those findings. Ashkan et al. showed in a single-center study conducted in UK that the overall number of patients referred for neurosurgical emergencies decreased between before and during the COVID19 pandemic. Concerning the oncological causes as well as the proportion of neurosurgical interventions due to brain tumor, the proportions of patients were stable during the COVID19 period: respectively 13.9% versus 11.4% before COVID19 and 17.9% versus 14.7% [14]. This stability in oncological neurosurgical activity was also observed in other centers [10], [15]. The proportion of patients who underwent tumor resection did not vary in our study: 68.7% in period 2 versus 64.1% in period 1, P = 0.23. These results are in line with those found in other centers [10], [16]. Surprisingly, we observed a higher proportion of tumor resection during the lockdown period: 81.4% (n = 79/174) versus 64.5% (n = 408/1366), P = 0.001. This difference is possibly explained by the best accessibility to the operating room during the period of lockdown in the studied centers.
Overall, COVIBRAIN study confirms that neurosurgical activity for a primary brain tumor was maintained during the COVID19 pandemic, both quantitatively and qualitatively. This findings highlight the non-follow-up of the recommendations proposing to postpone neurosurgery in selected situations: newly diagnosed low-grade glioma or high grade glioma in elderly and/or frail patients [4], [5]. MDT activity was also maintained during the entire epidemic period within the studied centers using virtual technology, as also described in Germany [17]. The impact of the COVID19 on neuro-oncological MDT should be investigated in regions with higher prevalence of Sars-Cov-2 infection, such as the Grand Est or the Île-de-France regions in France.
Finally, COVIBRAIN study did not explore the consequences of the COVID19 pandemic on the public health in neuro-oncology. The delay in oncological care beyond neurosurgery, the difficulty of access to healthcare structures, particularly for supportive care, Sars-Cov-2 intercurrent infections may have generated a significant reduction in survival during the pandemic period.
No difference in therapeutic decisions in MDT was observed in COVIBRAIN study. Nowadays, it would be interesting to assess the overall clinical consequences of the pandemic on the population of patients with a primary brain tumor in the Normandy region.
5. Conclusion
The number of cases presented to the neuro-oncology MDT did not vary significantly between the pre-COVID19 period and the initial phase of the pandemic in Normandy. Despite the hospital pressure of the pandemic on the care structures, the activity of neuro-oncology management was maintained. This maintenance was probably possible during 2020 thanks to the non-explosion of the number of hospitalized patients due to Sars-Cov-2. The consequences in terms of survival in this specific population should now be explored, in particular to investigate the possible impact of the delay within the care pathway of the patients.
Funding
No funding.
Disclosure of interest
The authors declare that they have no competing interest.
Acknowledgments
The authors thank Dr. Jean Rouvet (Cancer Center Henri-Becquerel) and Mrs. Dany Corban (Rouen University Hospital) for their help in collecting data.
Footnotes
Supplementary data associated with this article can be found, in the online version, at https://doi.org/10.1016/j.neuchi.2023.101429.
Appendix A. Supplementary data
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