Abstract
Background:
To assess the outcome of primary brain tumor radiotherapy with concurrent and adjuvant temozolomide.
Material and Methods:
A total of 42 patients who were histologically proven primary malignant brain tumor with nonmetastatic, ECOG (Eastern Cooperative Oncology Group) performance status 0, 1, and 2 were enrolled in this study.
Results:
All patients underwent craniotomy with gross total excision (GTE) 66.7% and partial excision 33.3%. Post craniotomy, patients were diagnosed as grade II 28.6%, grade III 23.8%, grade IV 42.9%, and glio-sarcoma 4.8%. Post radiotherapy with concurrent and adjuvant temozolomide, two years of overall survival were 83.3%, 60%, and 25% in grade II, grade III, and high-grade glioma, respectively.
Conclusion:
This study concluded that radiotherapy is an integral part of treatment in primary malignant brain tumor. Temozolomide (TMZ) in concurrent and adjuvant setting had additional survival benefit.
KEYWORDS: Brain tumor, radiotherapy, survival, temozolomide, toxicity
INTRODUCTION
Primary brain tumors can be both benign and malignant and are relatively infrequent. The clinical presentation of primary brain tumor is generalized or focal. Headache, seizures, and vomiting are the most common presenting symptoms. Focal neurologic deficits, such as weakness, language dysfunction, and sensory loss, are common in high-grade gliomas. According to GLOBOCAN 2020, the total burden of primary malignant brain tumor was 308102 and the total number of deaths were 251329. Male-to-female ratio was 1.3:1 worldwide.[1]
Malignant brain tumors can be classified into low-grade and high-grade gliomas. High-grade gliomas are heterogeneous in nature. Symptomatic benign and malignant tumors need surgical resection. Tumor resection depends upon factors like tumor location and expertise of the operating surgeon. After surgical resection of primary brain tumor, radiotherapy (RT) is necessary in high-grade and some low-grade gliomas. The purpose of radiotherapy in brain tumors is local tumor control and benefit in survival. Concurrent chemotherapy in the form of temozolomide (TMZ) with RT after surgical resection is the standard of treatment in high-grade gliomas. Adjuvant temozolomide after RT has a beneficial role in survival considering the age and performance status of patients.[2,3,4]
MATERIALS AND METHOD
A total of 42 patients who were histologically proven primary malignant brain tumor, were retrospectively enrolled in this study. All patients were registered in the Department of Radiotherapy at GURU GOBIND SINGH MEDICAL COLLEGE and HOSPITAL from JUNE 2016 to JUNE 2020. We ought to see the local tumor control after radiotherapy with concurrent and adjuvant chemotherapy in primary brain tumors and to assess the treatment-related toxicity profile. All the study group patients were assessed and observed weekly during radiotherapy period and at the end of the radiotherapy treatment. Patients were assessed for control of symptoms, treatment-related toxicities, and treatment response. All patients were followed up for two years. Every patient’s first follow-up was scheduled after one month of completion of radiotherapy. Patients were next followed up every three months in first year and at every six months in second year after completion of radiotherapy. On every follow-up, patients were assessed with CBC, RFT, LFT, MRI brain, and detailed clinical examination.
RESULTS
The mean age of patients in this study was 45.05 years and 23.8% of patients presented in the 31–40 years of age group. Males were more affected than females. Presenting symptoms in primary malignant brain tumors are headache, seizures, fatigue, and vertigo as shown in Table 1. Decreased vision, slurring of speech, and gait instability are seen in less number of patients. In the present study, seizures (42.9%), headache (19%), vertigo (9.5%), and a varied combination of the above symptoms (28.6%) were the chief complaints in patients, respectively. For histopathological confirmation, craniotomy was performed in all the patients. Craniotomy with gross total excision (GTE) and craniotomy with partial excision were performed in 28 (66.7%) and 14 (33.3%) patients, respectively. Post craniotomy, grade II 12 (28.6%), grade III 10 (23.8%), grade IV 18 (42.9%), and glio-sarcoma 2 (4.8%) were diagnosed in the study area after biopsy confirmation.
Table 1.
Demographic and clinical variables
| Characteristics | GROUP | Numbers | Percentage |
|---|---|---|---|
| Age in years | UP-10 | 2 | 4.8% |
| 11-20 | 0 | 0 | |
| 21-30 | 6 | 14.3% | |
| 31-40 | 10 | 23.8% | |
| 41-50 | 8 | 19% | |
| 51-60 | 8 | 19% | |
| 61-70 | 8 | 19% | |
| 71-80 | 0 | 0 | |
| Gender | Males | 22 | 52.4% |
| Females | 20 | 47.6% | |
| Residence | MALWA | 22 | 52.4% |
| MAJHA | 12 | 28.6% | |
| DOABA | 8 | 19% | |
| Symptoms | Seizures | 18 | 42.9% |
| Headache | 8 | 19% | |
| Vertigo | 4 | 9.5% | |
| Multiple | 12 | 28.6% | |
| Surgery | Craniotomy + GTE | 28 | 66.7% |
| Craniotomy + partial excision | 14 | 33.3% | |
| Diagnosis | Grade I | 0 | 0 |
| Grade II | 12 | 28.6% | |
| Grade III | 10 | 23.8% | |
| Grade IV | 18 | 42.9% | |
| Glio-sarcoma | 2 | 4.8% |
All patients received full course radiotherapy according to the diagnosis. All low-grade and high-grade glioma patients received RT dose of 54Gy/27#/5.5 weeks and 60Gy/30#/6 weeks, respectively. Temozolomide is given in concurrent setting with dose of 75 mg/m2 and in adjuvant setting with dose of 150–200 mg/m2. In first year, all patients were evaluated clinically and with MRI brain every three monthly. In second year of follow-up, all patients were evaluated at every six monthly with MRI brain and clinically. Seizures (42.8%) were the most common presenting complaint, followed by headache (19%) and vertigo (9.5%) in the present study. Slurring of speech (14.3%), decreased vision (19%), and weakness (9.5%) were also reported by patients. These symptoms decreased and subsided at three months of follow-up, except for headache, weakness, and decreased vision. Headache (28.5%) and weakness (45.2%) increased during the course of RT and subsided on subsequent follow-up. Decreased vision (9.5%) was the only complaint that did not subside. All patients received full course of the radiotherapy treatment with concurrent temozolomide. At completion of radiotherapy, 17 (40.4%) patients had grade 1 anemia, 13 (30.9%) patients had grade 1 neutropenia, and 15 (35.7%) patients had grade 2 thrombocytopenia. At one-month follow-up, one grade III patient died. At third- and sixth-month follow-up, two grade IV patients and one grade IV patient died, respectively. Five patients (four grade IV and one glio-sarcoma) died at nineth-month follow-up. Thirty-one patients (12 grade II, eight grade III, 10 grade IV, and one glio-sarcoma) were alive at one-year follow-up. Twenty-one patients (10 grade II, six grade III, four grade IV, and one glio-sarcoma) were alive at two-year follow-up. Two years of overall survival were 83.3%, 60%, and 25% in grade II, grade III, and high-grade glioma, respectively.
DISCUSSION
Post craniotomy, all patients were categorized into low-grade glioma and high-grade glioma on basis of histopathological report and immuno-histochemistry (IHC) confirmation. These patients were then taken up for radiotherapy with concurrent and adjuvant temozolomide as per departmental protocol. After IHC confirmation for high-risk features in low-grade glioma, radiotherapy was decided. EORTC Radiation oncology and brain tumor groups also show role of radiotherapy in low-grade gliomas with high-risk features.[4,5,6,7] Some studies show role of whole brain radiotherapy (WBRT) in malignant brain tumors,[8] but in our setting, IMRT or 3DCRT with concurrent and adjuvant temozolomide was preferred as per departmental protocol. Radiotherapy has a key role in the treatment of primary malignant brain tumors. It improves local control of disease and regression of symptoms. A study showed the effect of radiotherapy in terms of local control and improvement in the overall survival.[9] Another review article study also concluded that overall prognosis of high-grade gliomas was poor, but advanced imaging, radiotherapy, and newer cytotoxic drugs have improved the survival.[10] The radiotherapy treatment was started on time in all patients. EORTC 22845 randomized trial concluded that early radiotherapy improves progression free survival but does not affect the overall survival.[11] Addition of temozolomide in concurrent and adjuvant setting had beneficial effect. Temozolomide also helped in improving local and symptomatic control. In this study, all patients received temozolomide in concurrent setting with dose of 75 mg/m2, one hour prior to each fraction of radiotherapy. A study on survival concluded that concurrent TMZ and RT improved the median survival in elderly patients with favorable prognostic factors.[12]
All patients in this study also received adjuvant TMZ at a dose of 150–200 mg/m2 D1 to D5 in 28-day cycle. The patients were planned for adjuvant TMZ for 12 cycles, and each patient was evaluated for toxicity after every cycle. Adjuvant TMZ had a beneficial effect in low-grade glioma with high-risk factors and good performance status. A phase II study RTOG 0424 suggested OS and PFS outcomes exceeded with the RT-TMZ regimen.[13]
After one month of RT completion, three patients had anemia, seven patients had neutropenia, and five patients had thrombocytopenia. On subsequent follow-up, these toxicities resolved and no patient had toxicities at third-month follow-up. It was observed in a study that concomitant TMZ had treatment-related adverse toxicities and required close observation.[14] Another study concluded that survival was prolonged when TMZ was added to radiotherapy for GBM, which showed that two years of overall survival were 26%.[15]
CONCLUSION
Temozolomide (TMZ) in concurrent and adjuvant setting has additional survival benefit. Treatment-related toxicities, like nausea, vomiting, fatigue, and weakness, were manageable.
Conflicts of interest
There are no conflicts of interest.
Funding Statement
Nil.
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