Survival in patients with high-grade glioma was related to time period and age
In the population of 12765 HGG patients, demographics showed a peak in incidence in the sixth and seventh decade (fig 2). There was a highly significant difference (p < 0.001) in median survival between the three first time cohorts (1958-1969 [2.3 months; 80 days]; 1970-1979 [4.8 months; 145 days]; 1980-1989 [7.1 months; 213 days]) and a significant difference (p = 0.017) between the two last cohorts (1980-1989 [7.1 months; 213 days]; 1990-1999 [8.4 months; 252 days]) (fig 3a). When adjusted for the complete number of GBM five-year survivors in the 1990 – 1999 time cohort the median survival was reduced to 7.8 months; 233 days (fig. 3b). There was a tendency to an augmented number of HGG five-year survivors in the latter cohorts (table 1). After stratifying the population into different age cohorts (0-9; 10-19; 20-29; 30-39; 40-49; 50-59; 60-69; 70-79; 80 – w years) there was a stepwise significant difference between all age groups over 39 years (median survival 5.6 months ;168 days for the whole population and for the different age groups: 16.2/485; 20.5/615; 23.2/696; 17.2/517; 10.2/305; 6.9/206; 4.4/132; 2.4/73; 1.1/32 months/days respectively, p < 0.001) and only a partially significant difference in age groups < 39 years, with the highest median survival in the 20-29 cohort (fig. 4).
Five-year HGG survivors
736 (5, 8%) patients with registered HGG had a recorded five-year survival or more. The full pathology reports were reviewed in 585 cases and interpreted according to the 1993 WHO classification of Tumors of the Central Nervous System . The most common diagnosis was Anaplastic Astrocytoma (197 patients), followed by Astrocytoma grade II (86 patients), GBM (77 patients), Oligoastrocytoma grade III (34 patients), Pilocytic Astrocytoma grade I (27 patients), Oligodendroglioma grade II (26 patients) and Anaplastic oligodendroglioma grade III (24 patients). In eighteen cases no specific diagnosis was found. Three cases were intramedullary gliomas and nineteen were meningiomas that previously had been registered as HGG (table 2).
87 patients with a histopathological diagnosis of GBM (mitosis, hypercellularity, vascular proliferation and necrosis) were initially categorized as primary GBM. Patients with a previous diagnosis of diffuse low-grade glioma (DLGG), e.g. secondary GBMs and those with oligodendroglioma features were excluded. However, the primary GBM diagnosis was changed after additional surgery in 10 patients.
Thus, 77 patients were confirmed as primary GBM five-year survivors, constituting 0, 60 % of the total population of 12765 patients and 10, 5 % of 736 registered five-year survival HGG patients. 39 patients (51%) were male, 38 patients (49%) were female. The age at diagnosis ranged from 8-69 years with a median age of 41 years. Twenty-one patients were diagnosed in the age group 40-49 years, followed by 15 patients in 30-39 group, 14 patients in the 50-59 group, 12 patients in the 20-29 group, 8 patients in the 60-69 group, 6 patients in the 10-19 group, and 1 patient in the 0-9 age group (fig 5a). 55 patients (71%) were younger than 50 years and 22 patients (29 %) were older than 50 years when diagnosed.
Time periods and geographical location
Most GBM five-year survivors, 48 patients (62%), were diagnosed and treated in in the latter decades (1980-1989; 1990-1999) whereas 29 patients (38%) were treated in the earlier decades (1958-1969; 1970-1979) (table 1).
Symptoms and signs
Medical charts from four patients where the full pathology report had verified GBM diagnosis could not be retrieved. These patients were however included in the survey as five-year survivors. Charts from 73 GBM patients were reviewed. The most common presenting symptom was headache in 46 patients (63 %) followed by focal neurological signs in 38 patients (52 %), nausea and vomit in 28 patients (38 %), seizure in 26 patients (36 %) and vertigo in 18 patients (25 %). 6 patients (8%) had a history of autoimmunity (allergy, asthma, and other autoimmune diseases). No patients had multiple sclerosis. 6 patients (8%) have had previous head trauma. 3 patients (4 %) had a heredity of brain tumours and 6 patients (8 %) of other tumours. 5 patients (7%) have had previous non-CNS tumours, and none have had other brain tumours beside glioma.
Six patients (8%) had been treated for a general bacterial infection prior to surgery. 6 patients (8 %) developed a local, superficial wound infection postoperatively treated with oral antibiotics and 6 patients (8 %) had a deep postoperative infection treated with surgery, intravenous and later oral antibiotics. Three patients with local wound infection eventually developed and were treated for a deep wound infection. Thus, 9 patients (12 %) were treated for a deep postoperative wound infection. The median overall survival in patients with a postoperative infection was 2663 days (7,3 years) which was less than the overall survival in the non-infected population (median survival ≈ 9 years) (table 3).
51 patients (70%) had a preoperative Karnofsky functional status score > 70 and 22 patients (30 %) had < 70 (table 3).
GBM was located in the frontal lobe in 40 patients (55 %), temporal lobe in 14 patients (19%), parietal lobe in 8 patients (11 %), occipital lobe in 6 patients (8 %), ventricle in 2 patients (2,8 %), cerebellum and brain stem in 1 patient (1 %). In one patient (1 %) the tumour was multi lobular. 44 patients (60 %) had tumours in the right hemisphere whereas 29 patients (39 %) had tumours in the left. Forty-three tumours (59 %) were located superficially (< 1 cm below cortex), 30 tumors (41%) were deeply located (> 1 cm below cortex) (table 3).
36 patients (49%) were operated with Gross Total Resection (GTR) according to the surgeon’s report. 32 patients (44%) had partial resection and 5 patients (7 %) underwent a biopsy. 24 patients (33 %) had repeated surgery whereas 49 patients (67%) did not have any secondary surgery. Among patients with repeated surgery, 19 patients had one, 4 patients had two and one patient had three additional surgeries. Almost all, 69 patients (95%) received postoperative oncological treatment with full radiotherapy (56-60 Gy) whereas 4 patients (5 %) did not. 38 patients (52%) did also receive chemotherapy (table 3).
The full neuropathology reports were reviewed by the authors as described above. Thirty-three patient samples had been reexamined during the clinical course due to an unexpectedly long survival, warranting a new examination. In additionally twenty-four patients, the diagnosis of GBM was confirmed through iterated surgeries. In sixteen patients, no new evaluation had been made. Hence, in 57 out of 73 cases the GBM diagnosis had been reexamined and verified. Additional microscopic sample examinations were not performed by the authors.
Overall survival in GBM five-year survivors ranged between 5-55 years with a median survival of 3251 days or approximately 9 years (8 years, 11 months) (fig 5b). Ten patients were still alive in January 2020. Nineteen patients (24%) survived five but less than six years after diagnosis, representing the largest cluster in the cohort. Thirty-five patients (0.27%) survived more than ten years.