Case Study 3 Cns Cancer Symptoms

Abstract

Despite multimodal treatment, it is not possible to cure high-grade glioma (HGG) patients. Therefore, the aim of treatment is not only to prolong life, but also to prevent deterioration of health-related quality of life as much as possible. When the patient's condition declines and no further tumor treatment seems realistic, patients in the Netherlands are often referred to a primary care physician for end-of-life care. This end-of-life phase has not been studied adequately yet. The purpose of this study was to explore specific problems and needs experienced in the end-of-life phase of patients with HGG. We retrospectively examined the files of 55 patients who received treatment in our outpatient clinic and died between January 2005 and August 2008. The clinical nurse specialist in neuro-oncology maintained contact on a regular basis with (relatives of) HGG patients once tumor treatment for recurrence was no longer given. She systematically asked for signs and symptoms. The majority of the patients experienced loss of consciousness and difficulty with swallowing, often arising in the week before death. Seizures occurred in nearly half of the patients in the end-of-life phase and more specifically in one-third of the patients in the week before dying. Other common symptoms reported in the end-of-life phase are progressive neurological deficits, incontinence, progressive cognitive deficits, and headache. Our study demonstrates that HGG patients, unlike the general cancer population, have specific symptoms in the end-of-life phase. Further research is needed in order to develop specific palliative care guidelines for these patients.

end-of-life, high-grade glioma

Patients with high-grade glioma (HGG), the most frequently occurring primary malignant brain tumor, have a poor prognosis and cannot be cured. Despite aggressive multimodality treatment with surgery, radiation therapy, and chemotherapy, median survival ranges from <1 to 5 years depending on histological subtype, tumor grade, cytogenetic analysis, age, and performance status at the time of diagnosis.1,2

Focal neurological deficits, symptoms of increased intracranial pressure, epilepsy, and cognitive dysfunction are prominent symptoms in HGG patients which may arise in any stage of the disease.3–5 Furthermore, fatigue, mood disturbances, and anxiety are often reported.6 These factors all negatively affect health-related quality of life (HRQOL) of patients and their relatives.7–9 Antitumor treatment as well as supportive medication [often steroids and antiepileptic drugs (AEDs)] may cause side effects which may further diminish HRQOL.10,11 Since HGG patients cannot be cured, the aim of treatment is not only to prolong life, but also to maintain quality of life as long as possible. In this respect, HRQOL is included as a secondary endpoint in a growing number of randomized clinical trials evaluating antitumor treatment.12,13

When the patient's condition declines due to tumor progression and further tumor treatment is not an option, the end-of-life phase begins. In this phase, only supportive treatment is given.14 In the Netherlands, patients in this phase often no longer visit the neuro-oncology outpatient department and become dependent on care provided by primary care physicians. Depending on where the patient resides, the general practitioner, the nursing home specialist, or the hospice doctor is the coordinating physician. In the Netherlands, only a minority of cancer patients dies in hospitals, which probably also holds true for HGG patients.15,16

Patients and their relatives often are anxious about what will happen in the last phase of life.

Until now, there are limited data on the end-of-life phase of these patients.4,17–19 The few existing reports identified symptoms related to increased intracranial pressure (headache and drowsiness), as well as progressive neurological deficits, epileptic seizures, confusion/delirium, fatigue, and dysphagia as the most prominent symptoms.17–19

A better knowledge of the clinical issues for this specific group of patients in the end-of-life phase will improve the information given to future HGG patients and their families as well as the care supplied. We therefore explored the incidence of specific symptoms in the end-of-life phase in a group of HGG patients.

Patients and Methods

Patients

Adult (>18 years of age) glioma patients, who had died between January 2005 and August 2008 after being treated for their tumor at the VU University Medical Centre, Amsterdam, were considered for inclusion in the analysis.

Patients with either an initial histological diagnosis of HGG (glioblastoma multiforme, high-grade astrocytoma, high-grade oligodendroglioma, or high-grade mixed glioma) or a histological confirmed low-grade glioma (LGG), with clinical and radiological progression suspected for a high-grade tumor following initial treatment, were included. According to our definition, the end-of-life phase started once patients presented with progressive disease for which there were no further tumor treatment options, or if patients refused further tumor treatment. Patients who died during tumor treatment were therefore excluded.

Materials and Methods

In the end-of-life phase, patients no longer visited the outpatient clinic on a regular basis. The clinical nurse specialist, however, kept in touch with the patients and/or their families via a telephone service. Patients and caregivers were invited to call the clinical nurse specialist in the case of questions and problems. Otherwise, the clinical nurse specialist contacted the patients and/or their main informal caregiver(s) on a biweekly basis and asked for signs, symptoms, and problems encountered. In these telephone contacts, using a checklist, the clinical nurse specialist investigated the occurrence of pain, headache, focal neurological deficits, confusion, cognitive disturbances, seizures, and incontinence, as well as the level of consciousness, changes in medication (antiepileptics and steroids), and problems with intake of medication, fluid, and food (Fig. 1).

Furthermore, in the month following death, the course of the disease in the last week before dying was enquired after with the family or the primary care physician.

Symptoms, signs, and treatment in the end-of-life phase as a whole were retrieved from medical files and the chart of the clinical neuro-oncology nurse specialist. Symptoms and problems arising in the week before death were recorded separately.

Statistical Analysis

We used SPSS software 15.0 for statistical analysis.

Results

Demographic and Clinical Data

Seventy-five consecutive adult HGG patients, who ended all tumor treatment while being treated at our centre, and died between January 2005 and August 2008, were identified. Seventeen (relatives of) patients did not use the telephone service. Nine of these 17 were referred to another institution in the end-of-life phase and had a contact person there. The other 8 declined the service. Fifty-eight patients were included in this analysis. Of these 58 patients, 12 patients had been diagnosed with an LGG before dedifferentiation to an HGG.

Table 1 shows demographic and clinical data.

Table 1.

Demographic and clinical data (n = 58)

Sex 
 Male 39 (67%)a
 Female 19 (33%)a
Age at diagnosis (y) 52 (18–81)b
Grade 
 Grade III 15 (26%)a
 Grade IV 41 (71%)a
 Unspecifiedc2 (3%)a
History of LGG 12 (21%)a
Survivald in months 
 Grade III 21 (11–86)b
 Grade IV 12 (0.5–71)b
Length of the end of life phase, days 46 (1–294)b
Place of death 
 • At home 38 (66%)a
 • Hospital 10 (17%)a
 • Hospice 5 (8.5%)a
 • Nursing home 5 (8.5%)a
Sex 
 Male 39 (67%)a
 Female 19 (33%)a
Age at diagnosis (y) 52 (18–81)b
Grade 
 Grade III 15 (26%)a
 Grade IV 41 (71%)a
 Unspecifiedc2 (3%)a
History of LGG 12 (21%)a
Survivald in months 
 Grade III 21 (11–86)b
 Grade IV 12 (0.5–71)b
Length of the end of life phase, days 46 (1–294)b
Place of death 
 • At home 38 (66%)a
 • Hospital 10 (17%)a
 • Hospice 5 (8.5%)a
 • Nursing home 5 (8.5%)a

View Large

Symptoms and Signs in the End-of-Life Phase

Three of the 58 cases were lost to follow-up in the end-of-life phase and therefore excluded. Two of these patients died in a nursing home, and 1 passed away at home. In Table 2, symptoms and signs occurring anytime in the end-of-life phase are depicted.

Table 2.

Symptoms documented anytime in the end-of-life phase (n = 55)

Symptoms Number of patients (%) 
Drowsiness/progressive loss of consciousness 48 (87) 
Dysphagia 39 (71) 
Progressive focal neurological deficits (motor, dysphasia) 28 (51) 
Seizures 25 (45) 
Incontinencea22 (40) 
Progressive cognitive deficits 18 (33) 
Headache 18 (33) 
Confusion 16 (29) 
Bodily pain 14 (25) 
Symptoms Number of patients (%) 
Drowsiness/progressive loss of consciousness 48 (87) 
Dysphagia 39 (71) 
Progressive focal neurological deficits (motor, dysphasia) 28 (51) 
Seizures 25 (45) 
Incontinencea22 (40) 
Progressive cognitive deficits 18 (33) 
Headache 18 (33) 
Confusion 16 (29) 
Bodily pain 14 (25) 

View Large

The most frequently reported symptom was decreased consciousness (87% of the patients) which, however, was not reported until the last week before death in the majority of patients (73% of these patients). The second most common symptom was dysphagia. This occurred in 71% of the cases and often coincided with decreased consciousness. Fifty-two percent of the patients experienced progressive neurological deficits (motor deficit, coordination loss, and/or aphasia). Seizures were reported in 45% of all patients in the end-of-life phase. Of patients who already had seizures during the course of disease, 53% also had seizures in the end-of-life phase. Conversely, of patients who had been free of seizures so far, 11% had their first seizure in the end-of-life phase. Thirteen (52%) of the 25 patients who had seizures in the end-of-life phase had more than 1 seizure in this phase. All patients with seizures received AEDs. Among the patients who were on anticonvulsive drugs, there were no patients who never had epileptic seizures. In 40% of the patients, incontinence was reported to occur before the patients were bed-ridden. Headache, progressive cognitive deficits (memory loss, personality changes, apathy, and problems in executive functioning and understanding), and agitation/confusion all were reported in one-third of the patients. Next to headache, 25% of the patients reported bodily pain, often related to immobilization.

Additionally Reported Symptoms

In addition to the symptoms and signs structurally asked for, other symptoms and signs which were additionally reported by the patients and their caregivers are given in Table 3. Twenty-five percent of the patients experienced severe fatigue and 20% of the patients suffered from nausea or vomiting. Dyspnea was reported in 9 patients (16%): in 5 cases, this was most likely due to pneumonia, in 1 patient due to pulmonary embolism, whereas in the remaining 3 cases, the cause of dyspnea was unclear. Constipation, probably due to morphine use, was severe enough to be reported in 5 cases. In 5 patients, symptoms of anxiety and/or depression were mentioned. One patient had severe vertigo due to tumor infiltration in the 8th cranial nerve. Severe side effects from steroid use were reported in 4 cases: 2 patients suffered from steroid myopathy, 1 patient developed hyperglycemia, and 1 patient had a bowel perforation while using steroids. Overall, 44 (80%) patients used steroids in the end-of-life phase.

Table 3.

Additionally reported symptoms (n = 55)

Symptoms Number of patients (%) 
Fatigue 14 (25) 
Nausea/vomiting 11 (20) 
Dyspnea 9 (16) 
Constipation 5 (9) 
Anxiety/depressive symptoms 5 (9) 
Symptoms Number of patients (%) 
Fatigue 14 (25) 
Nausea/vomiting 11 (20) 
Dyspnea 9 (16) 
Constipation 5 (9) 
Anxiety/depressive symptoms 5 (9) 

View Large

Symptoms in the Week Before Dying

Although drowsiness was only present in 13 patients (24%) at the start of the week before dying, this number increased to 48 patients (87%) during the last week. This also holds true for dysphagia: the number increased from 5 patients (9%) to 39 patients (71%). In the last week, 28% of all patients experienced at least 1 seizure.

Cause of Death

In 40 patients (73%), the presumed cause of death was brain herniation due to tumor progression. For 4 other patients, the cause of death was directly tumor-related; these patients died following a seizure (3 patients) or a hemorrhage in the tumor (1 patient). For 8 patients, the cause of death was indirectly tumor-related; 5 patients died due to an infection (in 2 cases, this concerned an aspiration pneumonia following a seizure), 1 died from bowel perforation while using steroids, 1 patient died from pulmonary embolism, and 1 suffered traumatic brain damage following an accident and died from urosepsis. In 3 patients, euthanasia was performed under strict conditions upon a voluntary and well-considered request.

Discussion

The most commonly reported symptoms in the last phase of our cohort of HGG patients were drowsiness (87%), dysphagia (71%), progressive neurological deficits (51%), seizures (45%), incontinence (40%), progressive cognitive deficits (33%), and headaches (33%). Of these, drowsiness and dysphagia appeared to occur most frequently in the week before death.

One of the drawbacks of this study is the focus on symptoms specific for brain tumors. The more general end-of-life symptoms reported in extracranial cancer patients, such as fatigue, mood disturbances, nausea, and constipation, are probably underreported as these were not structurally asked for.20,21 Another restraint is the relatively small number of patients. Despite these limitations, our data are worth reporting, given the lack of studies in this field.

In 3 earlier studies in patients dying from brain tumors, comparable prevalence rates of increased intracranial pressure symptoms (drowsiness and headache), neurological deficits, seizures, and cognitive deficits were reported.17–19 The occurrence of dysphagia, however, differed among these studies. Dysphagia was reported in 70% of our cases, more or less comparable to the studies by Oberndorfer et al.17 and Pace et al.18 In contrast, Faithfull et al.19 described a prevalence of only 10%. This discrepancy in prevalence rates is probably due to the fact that we also denominated patients to be dysphagic if they were unable to swallow due to loss of consciousness. If these patients are excluded, only 14% had (true) dysphagia.

The high prevalence of swallowing difficulties in the last week of life may yield problems in taking medication. The majority of patients used AEDs and/or glucocorticoids (dexamethasone) in the last phase of life. About one-third of the patients suffered from seizures in the last week of life and these may be life-threatening as appeared to be the case in 5 patients. Since seizures are even a more prominent feature in the end-of-life phase than we had anticipated, continuation of AEDs should therefore be recommended, even if oral administration is no longer possible. In view of the fact that most patients stay at home or in a first-line care setting, a noninvasive administration route is preferred when patients are unable to swallow at the end of life. Rectal administration of carbamazepine, valproic acid, and phenobarbital is available. Otherwise, seizures may be treated with rectal diazepam, intranasal or subcutaneous midazolam or sublingual clonazepam.22 In the hospital setting, intravenous infusion should be considered.

Urinary incontinence has not been described in former reports concerning the end-of-life phase of brain tumor patients. In our cohort, it was a relatively early and prominent sign (before the patient was confined to bed) occurring in 41% of the cases. Incontinence has often been associated with immobilization, social withdrawal, body image distortion, and depression and thus has a major impact on quality of life.23 Urinary incontinence, specifically in brain tumor patients, can be caused by the tumor itself, such as may be the case in frontal tumors, or due to impaired cognition and consciousness. Other (reversible) causes may be urinary tract infection, hyperglycemia, and the use of sedatives.23 In a general cancer population, 29% of the patients were incontinent for urine in the end-of-life phase.24 Thus, the prevalence of incontinence appears to be relatively high in brain tumor patients.

Of further interest is to compare the prevalence of more “general” end-of-life symptoms in HGG patients with other cancer patients. The main symptoms reported in terminally ill cancer patients are fatigue and anorexia, followed by pain, nausea, constipation, delirium, and dyspnea.20,21 As noted before, these symptoms are probably underreported in our patients, since we did not ask for general symptoms. However, bodily pain was asked for and appeared to occur less frequently in glioma patients (25%) when compared with patients with systemic cancer, where prevalence rates of 60%–80% are reported.24 Despite the fact that we are still unaware of the prevalence of general symptoms in glioma patients in the end-of-life phase, the disease-specific symptoms are prominent. This indicates that the end-of-life phase of HGG patients cannot be compared simply with a general cancer population. Future studies prospectively exploring the end-of-life phase of HGG patients are mandatory in order to develop specific palliative care guidelines for these patients and their relatives.

Conflict of interest statement. None declared.

Funding

This work was supported by the St Jacobusstichting, The Hague (E.M.S., M.J.B.T).

References

Case presentation – A five-year survival of the patient with glioblastoma brain tumor

Hubert Urbańczyk,a,Anita Strączyńska-Niemiec,bGrzegorz Głowacki,aDariusz Lange,b and Leszek Miszczyka

aCentrum Onkologii, Instytut im. Marii Skłodowskiej-Curie, Oddział w Gliwicach, Zakład Radioterapii, Poland

bCentrum Onkologii, Instytut im. Marii Skłodowskiej-Curie, Oddział w Gliwicach, Zakład Patologii Nowotworów, Poland

Hubert Urbańczyk: lp.eciwilg.oi@trebuh: moc.liamg@kyzcnabru.a.trebuh

Corresponding author at: Centrum Onkologii, Instytut im. Marii Skłodowskiej-Curie, Oddział w Gliwicach, Zakład Radioterapii, 44-101 Gliwice, ul. Wybrzeże Armii Krajowej 15, Poland. Tel.: +48 609 139840. lp.eciwilg.oi@trebuh, moc.liamg@kyzcnabru.a.trebuh

Author information ►Article notes ►Copyright and License information ►

Received 2013 Jan 31; Revised 2014 Feb 27; Accepted 2014 Apr 5.

Copyright © 2014 Greater Poland Cancer Centre. Published by Elsevier Urban & Partner Sp. z o.o. All rights reserved.

This article has been cited by other articles in PMC.

Abstract

This paper presents an atypical case of a patient with brain tumor of the glioblastoma multiforme (GBM) type who achieved a 5-year survival. Some general information is provided including epidemiology, diagnostic and treatment procedures (surgery and radio-chemo-therapy), and prognosis of survival related to GBM. The course of the disease, including its main symptoms, individual reasons for the delay of adjuvant treatment, after the primary surgical treatment, 37-month period of the decease free survival, as well as comprehensive management after the tumor recurrence are also presented. Histopathology confirming the clinical diagnosis is discussed in a separate chapter.

Keywords: Glioblastoma, Survival, Brain tumors, Treatment, Radiotherapy

1. Background

Primary brain tumors account for about 2% of all malignant neoplasms in adults. Approximately a half of them represent gliomas, derived from neuroepithelial cells, among which glioblastoma (GBM) is the most common type.

GBM cases represent about 20% of all primary brain tumors in the adult population, and about 75% of all the anaplastic gliomas.1 The prevalence of GBM is about 2–4 cases per 100,000. It is more common in men than in women, and its incidence increases with age.2 Only sporadically, GBM can be found in individuals younger than 20 years of age, and its frequency rapidly increases, starting from the 5-th decade of life.

The treatment results of patients diagnosed with GBM are often unsatisfactory, and the outcome is usually poor. Currently, the main standard therapeutic methods include a radical surgical procedure, combined with radio-chemo-therapy. Some innovative methods of radiotherapy based on the application of novel radiosensitizers of corpuscular irradiation or radio-immune-therapy are now being investigated. A median survival time of patients diagnosed with GBM, treated only with the use of neurosurgical procedures are 3–5 months. The application of conventional adjuvant radiotherapy prolongs this average time about 3-fold, with a three-year survival for only about 6% of patients.

The post-treatment survival time depends on many clinical factors, such as general patient condition, age, and histopathological type of the tumor. Simson et al. demonstrated statistically significant longer survival periods among patients in whom the primary tumor location was in the frontal lobe, in comparison to the ones in whom it was located in the parietal or temporal cerebral region (11.4 months vs. 9.6 months vs. 9.1 months, respectively; p = 0.01).3 Severity of neurological symptoms, limits of the performed surgical procedures, and response to the applied therapy, based on imaging tests, also represent prognostic factors.

Etiology of malignant neoplasms of the central nervous system (CNS) is still unknown. The most common of many probable carcinogens include: nitrosamines, pesticides, herbicides, petrochemical substances, polyvinyl chloride, and electromagnetic irradiation. However, the role of these pro-carcinogenic factors has not been unequivocally proven.4,5 In contrast, it has been documented that patients exposed to ionizing irradiation have an increased risk of the CNS malignant gliomas. According to the current state of knowledge in the field of molecular biology and genetics of these malignancies, two main hypotheses related to their development have been proposed. The first one includes de novo creation which is related to the loss of heterozygotic properties in chromosomes 9p, 10, 17p, and with the amplification of genes for the EGFR and CDK4 (this type of malignant growth occurs more often in older patients). The second one involves the creation of anaplastic gliomas, through the progression of gliomas with a lower malignancy grade (encountered more often in younger patients).6,7

Currently, a required standard of therapy for patients with GBM is a combined treatment, including tumor resection, with following concomitant radio-chemo-therapy, and adjuvant chemo-therapy, based on Temozolomide. In patients who undergo non-radical surgery, or who are not treated surgically, the palliative whole brain radiotherapy (WBRT), stereotactic radiation surgery (SRS), or combination of both of these therapeutic methods are used. Also, the application of palliative chemotherapy and symptomatic treatment remain important. In addition, alternatively fractionated radiotherapy, brachytherapy, targeted molecular therapy, radio-immune-therapy, hadrone therapy, or radio-sensitizers can be considered in individual cases.

In 2005, Stupp et al. presented results of a randomized study conducted by EORTC (European Organization for Research and Treatment of Cancer) and NCIC (National Cancer Institute of Canada), comparing the application of combined radio-chemo-therapy based on Temozolomide and radical radiotherapy alone. The combined management in a statistically significant manner prolonged the total survival time from 12.1 to 14.6 months, and the rate of 2-year survival was 26.5%, compared to 10.4% for radiotherapy alone.8 The follow-up results, after a longer period of observation, confirmed the previous reports. The 2-, 3-, and 4-year survival rates were 27.3%, 16.7%, and 12.9%, respectively (p < 0.0001) in the patients’ group treated with a combined therapy, and 11.2%, 4.3%, and 3.8%, in the patients’ group treated with radiotherapy only.9

Unfortunately, despite the use of Temozolomide, the results are unsatisfactory. The reason for this therapeutic failure is the GBM resistance to most chemotherapeutic agents or rapid development of the GBM as a result of genetic transformations within the tumor cells. The main mechanism of the GBM resistance to alkylating agents, such as temozolomide, procarbazine, or nitrogen mustard derivatives, is the repair of damages caused by these drugs with involvement of protein coded by MGMT (O6-methyl-guanine-DNA methyl-transferase) gene.

A degree of methylation of the promoter's region of MGMT gene appears to be closely correlated with a therapeutic response of the glioma cells. Hypermethylation of this part of the gene significantly increases treatment efficacy among patients treated with Temozolomide,10 influencing their survival period, as well.9

2. Case presentation

The patient is a 38 year old Caucasian male, smoker (about 10–15 cigarettes per day for 20 years), without other relevant family or personal risk factors for neoplasic disease who had suffered from severe headaches and nausea (his first disease symptoms) since August of 2005. He did not seek any medical help until November of 2005, when he presented to his doctor, due to exacerbation of those symptoms. No abnormalities on both physical and neurological examinations were detected at that time.

On December 30th of 2005, the CT scan of his brain was remarkable for the following findings: “An expansive lesion of approximately 5 cm × 3 cm in size, located in the right temporal lobe, with nonhomogenic, post-contrast signal amplification. A large edema surrounding the lesion. A compression of the occipital corner of the right lateral ventricle. A slight enlargement of the supratentorial ventricular system, shifting to the left.”

On January 25th of 2006, the patient underwent surgical therapy, including right temporal craniotomy, with total resection of the tumor. On February 7th of 2006, a histopathology examination (identification number 475,958; Info-Pat, Poznań, Poland), confirmed a diagnosis of the GBM IV stage (according to WHO classification). Microscopic images of the tumor are presented (Figs. 1–5).

Fig. 1

Microscopic image of patient's tumor.

Fig. 2

Microscopic image of patient's tumor.

Fig. 3

Microscopic image of patient's tumor.

Fig. 4

Microscopic image of patient's tumor.

Fig. 5

Microscopic image of patient's tumor.

After the surgery, the patient was referred to the Institute of Radiation Oncology in Gliwice, Poland, for the post-operative radiotherapy. Although the patient was qualified for this treatment, he did not arrive to the Institute of Radiation Oncology on the day of the scheduled preparatory procedures. The reason for his absence was a simultaneous diagnostic finding of the left lung's tumor, for which the patient underwent a thoracotomy with the wedge tumor resection (for diagnostic purposes). On June 12th of 2006, based on the histopathological examination results, which showed post-tuberculosis lesions, the patient's pulmonary treatment was completed.

In February 2007, approximately 13 months after his brain tumor surgery, the patient again presented to the Institute of Oncology, and according to the follow-up diagnostic work-up, no brain tumor recurrence was found. Due to the absence of tumor, no radiotherapy was considered, and “watchful waiting” was recommended including brain imaging studies (CT or MRI) to be repeated every 3 months. In the face of the atypical disease course, an additional verification of the histopathological diagnosis was also performed, confirming the original findings of the GBM. The patient had remained under close control until February 2009 (37 months from his initial brain tumor surgery), and at that time the brain tumor recurrence was found. His recurrent tumor was located in the primary tumor's bed, and its size was 4 cm × 5.3 cm × 3.5 cm (Fig. 6). However, those findings were not associated with any particular symptoms or abnormalities on subsequent physical or neurological examinations of the patient. On March 16th 2009, the patient underwent another craniotomy with the subtotal tumor resection. (MRI scans after the second craniotomy are shown in Figs. 7 and 8.) The histopathology examination was again consistent with GBM. During the period from May 11th to June 19th of 2009, the patient received the radiotherapy dose of 60 Gy/30 fractions to the tumor lodge, including the residual tumor, with 2.5 cm of tissue margin. Due to the lack of the patient's consent, no chemotherapy was implemented. During the irradiation period, he had the first seizure episode, and was started on antiepileptic therapy (Depakine 200 mg a day). He continued this therapy for the rest of his life. After the radiotherapy, diagnostic follow-up examinations were conducted every 3 months. At the beginning of March 2010, another recurrence was found, and the tumor was localized in an upper part of the tumor bed, within the previously irradiated area (its size was 3.7 cm × 2.6 cm × 2.3 cm). Surprisingly, the patient had not experienced any symptoms, and his physical and neurological examinations were unremarkable. On March 13th of 2010, the stereotactic radiotherapy, using a single dose of 8 Gy applied to the area of recurrent tumor was performed. Unfortunately, on the control examination, on July 6th of 2010, further progression of the GBM was found. The patient expired on November 15th of 2010, in the local hospital (Zawiercie, Poland), due to the tumor expansion, resulting in cerebral edema, herniation, and multi-organ failure.

Fig. 6

CT scan of recurrence tumor.

Fig. 7

MRI scan after the second craniotomy.

Fig. 8

MRI scan after the second craniotomy.

3. Histopathology examination

On a histopathology specimen, the large areas of thrombotic necrosis, most probably caused by a large tumor size (5 cm × 3 cm) were found. In contrast, no “palisade” necrosis (with the characteristic palisade-like cell arrangements), typical for this type of tumor, was found.

Within vital tumor structures, a high cellular polymorphism was found. Besides some small calls (with hyperchromatic nucleus and scarce amount of cytoplasm), mostly atypical cells (giant, multisided or oval, with numerous nuclei with abnormal shapes, and visible nucleoli) were present. The cells revealed a strongly positive GFAP reaction that can be indicative of their glioma-type origin. Also, some distinctive GBM features, including proliferation of vascular endothelium (focal areas of numerous mitotic figures, in high power field – HPF), were visible. The described microscopic images are presented in Figs. 1–5 (the images of primary and recurrent tumors appear identical).

4. Summary

In this paper, we presented a remarkably long survival period (63 months since the initial onset of symptoms, and 58 months since the primary surgical treatment) of the GBM patient. An important message from our case study that could be useful in the management of many other GBM cases is that the initial complete resection suggests a beneficial role of radical neurosurgery in the early GBM treatment and potential survival period.

Unfortunately, we are unable to indicate the specific reasons for such a long survival of our relatively asymptomatic patient who experienced some disadvantages, including the second malignancy, which caused the delay in the application of his radiotherapy.

Nevertheless, it should be emphasized that personalized, patient-centered approach, using comprehensive diagnostic and therapeutic strategies, as well as vigilant, multi-level follow-up care, should be helpful in explaining different factors, contributing to overall survival. In addition, our single case presentation illustrates several challenges that are common to many GBM patients, and merit further, more individualized research on this devastating disease.

Conflict of interest

None declared.

Financial disclosure

None declared.

References

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7. Lang F., Miller D., Koslov M. Pathways leading to glioblastoma multiforme. A molecular analysis of genetic alternations in 65 astrocytic tumors. J Neurosurg. 1994;81:427.[PubMed]

8. Stupp R., Mason W., van den Bent M. Radiotherapy plus concomitant and adjuvant temozolomide for glioblastoma. N Engl J Med. 2005;352(10):987–996.[PubMed]

9. Mirimanoff R., Mason W., Stupp R. Is long-term survival in glioblastoma possible? Updated results of the EORTC/NCIC Phase III Randomized Trial on radiotherapy (RT) and concomitant and adjuvant Temozolomide (TMZ) versus RT alone. Rad Oncol Biol Phys. 2007;69:S2.

10. Hegi M., Diserens A., Gorlia T. MGMT gene silencing and benefit from temozolomide in glioblastoma. N Engl J Med. 2005;352:997–1003.[PubMed]

Articles from Reports of Practical Oncology and Radiotherapy are provided here courtesy of Elsevier

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