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ORIGINAL ARTICLE
Ahead of print publication  

Hypofractionated reirradiation by conformal radiotherapy techniques in recurrent anaplastic astrocytoma and glioblastoma multiforme: An observational study at a Tertiary Care Center in North India


 Department of Radiation Oncology, Sheri Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir, India

Date of Submission27-Jan-2022
Date of Decision25-Feb-2022
Date of Acceptance09-Mar-2022
Date of Web Publication02-Aug-2022

Correspondence Address:
Tauseef Ahmad Tali,
Department of Radiation Oncology, Sheri Kashmir Institute of Medical Sciences, Srinagar, Jammu and Kashmir
India
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/jrcr.jrcr_10_22

  Abstract 

Aim and Objectives: The aims and objectives of the study were to assess the progression-free survival (PFS) and overall survival, local tumor control rate (response rate), effect on the quality of life, and treatment-related toxicities in all patients diagnosed with recurrent high-grade gliomas (HGGs). Methodology: The present study was conducted between September 2017 and July 2019 in the Department of Radiation Oncology, Sheri Kashmir Institute of Medical Sciences and included a total of 22 patients. The study included recurrent HGGs (Grade III/IV) Operated Cases of Grade III and Grade IV. Results: The majority of our patients were between the age group of 40–60 years (45.5%). There were 12 males (54.5%) and 10 females (45.5%). GBM was the most common diagnosis in 13 (59.1) patients and 9 (40.9%) were anaplastic astrocytoma. Sixteen patients were diagnosed as recurrent HGG radiologically. Sixteen (72.7%) patients achieved partial response and 6 (27.3%) achieved stable disease. The median PFS was 2.8 months and the median overall survival was 4.2 months. Conclusion: Reirradiation is one of the treatment options for recurrent HGGs and conformal intensity-modulated radiotherapy can be effective treatment modality for recurrent high-grade brain tumors with only mild side effects. Although survival is better in patients with good performance status and young age.

Keywords: Conformal radiotherapy techniques, high-grade gliomas, quality of life, reirradiation, survival, treatment-related toxicities



How to cite this URL:
Sofi SR, Tali TA, Kitab WA, Sofi MA, Lone MM, Najmi AM, Dar NA. Hypofractionated reirradiation by conformal radiotherapy techniques in recurrent anaplastic astrocytoma and glioblastoma multiforme: An observational study at a Tertiary Care Center in North India. J Radiat Cancer Res [Epub ahead of print] [cited 2022 Dec 4]. Available from: https://www.journalrcr.org/preprintarticle.asp?id=353190


  Introduction Top


High-grade gliomas (HGGs) are the most common malignant primary brain tumors in adults[1] and are associated with poor prognosis. Despite optimal therapy, nearly all HGGs eventually recur. The median survival following recurrence is only 25–30 weeks for the World Health Organization (WHO) Grade IV gliomas and 39–47 weeks for the WHO Grade III gliomas.[2],[3] Recurrence, despite therapy, is a hallmark of HGG, eventually occurring in all patients. Treatment of recurrent disease must be individualized, depending on a patient's clinical condition, performance, status, age, stage of treatment, and disease status. Over the past two decades, treatment strategies have become more aggressive, with an increasing number of patients being offered reoperation and reirradiation. Multiple recently published studies have proposed the importance of extent of resection and the number of operations at the time of recurrence to prolong survival in patients with HGG.[4],[5] Surgery is necessary for histopathological verification of tumor recurrence. Most data regarding treatment options in recurrent HGG are based on noncomparative phase 2 clinical trials, owing to the limited efficacy of many agents and the absence of a standard of care. Treatment regimens may include surgery, radiation, conventional chemotherapy, novel therapies, or a combination of these. The past decade has seen an explosion in the number of novel therapies, primarily because of our increased understanding of the molecular pathways important for disease progression.


  Methodology Top


The present study was conducted between September 2017 and July 2019 in the Department of Radiation Oncology, Sheri Kashmir Institute of Medical Sciences and included a total of 22 patients. Written Informed consent was taken before enrolling patients in this study and complete pretreatment assessment was done The aims and objectives of the study were to assess the progression-free survival (PFS) and overall survival, local tumor control rate (response rate), effect on the quality of life (QOL), and treatment-related toxicities in all patients diagnosed with recurrent HGGs. The study included recurrent HGGs (Grade III/IV) Operated Cases of Grade III and Grade IV and had already treated with surgery followed with radiotherapy with or without chemotherapy. Patients with age <18 years and low performance score (Karnofsky performance status [KPS]<70) were excluded from the study. Pretreatment evaluation included complete history taking and physical examination, baseline investigations including computed tomography/magnetic resonance imaging (MRI) brain, previously received radiation and chemotherapy details including radiation field size, portals used, and dose of radiation received. All patients were treated with hypofractionated protocol by three-dimensional conformal radiotherapy and intensity-modulated radiotherapy (IMRT) techniques, dose, and fractions intended (20 Gy in five fractions over 1 week) using linear accelerator. The gross tumor volume (GTV) taken as whole gross disease and surrounding edema, planned target volume taken as expansion of 1 cm margin of GTV. All patients were assessed for response with MRI brain 8 weeks after reirradiation.

Data analysis

Data analysis was done on a Microsoft Windows-based PC computer. The data were first keyed into a Microsoft Excel spreadsheet and cleaned for any inaccuracies. Statistical analysis was done using IBM SPSS Statistics for Windows from IBM Corp. (released 2020, Version 27.0. Armonk, NY, USA). Categorical variables were shown in the form of frequencies and percentages. Survival was calculated using the Kaplan–Meier method.

Ethics

This study was approved by the institutional ethics committee number IEC SKIMS protocol number RP-29/2018, dated 28/06/2018.


  Results Top


The majority of our patients were between the age group of 40 and 60 years (45.5%). There were 12 males (54.5%) and 10 females (45.5%). GBM was the most common diagnosis in 13 (59.1) patients and 9 (40.9%) were anaplastic astrocytoma. All cases were diagnosed either by histopathologically or radiologically. Recurrent median tumor size was 5.5 cm (range 2.5 cm–6.2 cm). Of 22 patients, six patients were reoperated. All reoperated patients were young with good performance status. Sixteen patients were diagnosed as recurrent HGGs radiologically. Sixteen (72.7%) patients achieved partial response and 6 (27.3%) achieved stable disease. The majority of patients, 20 (90.9%) have fatigue followed by nausea 12 (54.5%) patients. The median PFS was 2.8 months and the median overall survival was 4.2 months [Table 2].
Table 1: Baseline characteristics of the study population

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Table 2: Outcome and treatment-related toxicities

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  Discussion Top


Enrolled age of patient ranged from 20 to 65 years. Total of 10 patients (45.5%) being the age group of 40–65 years followed by eight patients (36.4%) with the age group of 20–40 years and more than 60 years comprised only four patients (18.2%). Our results were almost similar with the study done by Ostrom QT et al. in 2014[6] that showed increase in incidence of anaplastic astrocytoma and GBM with age peak observed in the 65–70 year group, this observation may be attributed to more life expectancy in that population as compared to ours. Most of the patients were males with a male and female ratio of 1.5:1 [Table 1]. Our results were comparable with other studies done by Conti A et al. 2017,[7] in which males were 24 of 43 patients, another study by Ulutin et al.[8] in which male–female ratio was 2:1.

Enrolled patients were followed for treatment-related complications of radiotherapy with observation as fatigue in 20 patients (90.9%), headache in eight patients (36.3%), nausea in 12 patients (54.5%), and somnolence in 10 patients (45.4%). Our study is comparable with Selch MT et al.[9] studies the central nervous system complications of brain radiotherapy and they summarized treatment-induced toxicities, remains a major cause of morbidity in patients with cancer and most common complication was fatigue. In a study by Emory et al., acute toxicities, such as fatigue was one of the most prominent acute toxicities associated with brain radiation and were experienced within the first few days to weeks of treatment. Our results are comparable with this study (Emory et al.). The patients were divided as per histopathology, the most common type was GBM in 13 patients (60%) and anaplastic astrocytoma (Grade III) in nine patients (40%). The observations in our study were comparable to other studies such as Xiaofeng et al. found pathological diagnosis as GBM 68.5% and anaplastic astrocytoma 18.5%. Post reirradiation radiotherapy, MRI brain was done after 6–8 weeks of completion of treatment to see response assessment.

The treatment response was assessed by contrast-enhanced MRI brain 8 weeks after completion of treatment. Sixteen (72.7%) patients achieved partial response, stable disease was observed in six (27.3%) patients, complete response was not achieved. The treatment protocol was well-tolerated with only mild side effects, the majority of patients had fatigue 90.9%, no Grade 3 or 4 toxicity was recorded. All patients progressed and died. Median follow-up time from reirradiation was 12.3 months (range 2.5–16 months). Median overall survival after reirradiation was 4.2 months (range 3–23 months) and PFS was 2.8 months (range 1–13 months). Our results are comparable with the study done by Ferrat Dincoglan et al., in this study, a total of 28 patients analyzed. They showed that median follow-up was 13 months (range 2.6–18.2 months) and at the time of analysis, 17 (56.8%) patients progressed and 12 (41.3%) patients have died. Median PFS was 2.6 months (range 0–14 months) and median overall survival was 4.1 months (range 3–16 months). There are several studies of reirradation in HGG where patients had been treated with external beam radiotherapy (mean dose 23.33 Gy). These studies have -hown a median survival of 6 months with reirradiation; however, no severe toxicity was reported in these studies.[7],[9],[10]

Regarding the QOL measurements in this study, the median values were lower for physical functioning (PF), emotional functioning (EF), and social functioning (SF). Thus, the patients reported more difficulties in these domains than role functioning (RF) and cognitive functioning (CF). These domains are significantly related to the age factors. Social, psychological, and EF support networks and play a critical role in patients diagnosed with malignant glioma.[11],[12] Our study results are consistent with the study done by Mahalaxmi and Venisree et al. who found that both low and HGG (LGG and HGG) patients had poor mean scores in SF (87.0), PF (82.0), EF (75.2), and RF (58.9). The mean scores on CF (61.9) and global QOL (60.3) were better. Age, KPS, and WHO grades showed significant associations with all functional scales. The percentage values were higher for symptoms of fatigue (76.9%), pain (71.5%), financial difficulties (77.6%), and appetite loss (38.46%) in both LGG and HGG. Similarly, with respect to QLQ-BN20 domains, HGG patients showed more symptoms than low grade with a significant correlation in communication deficit problems (P = 0.02), headache (P = 0.073), seizures (P < 0.125), and hair loss (P < 0.012) than the other symptoms. This initial assessment suggests that an increasing burden of symptoms exists, with poor QOL and survival, which has become a major concern in different grades of glioma patients. However, in contrast to our study, this study compared QOL measured between low and HGGs, whereas our study was only about QOL in HGGs (GBM). One of our objectives was to assess the overall survival rate and PFS rate with a median follow-up of 11 months. In our study, we found that the median overall survival rate was 4.2 months (3–23 months) and median PFS was 2.8 months (Range 1–13 months). Our longest follow-up was of 23 months while the shortest one was of 3 months. As such the results of our study almost coincide with the studies of Kwan Ho Cho et al., who observed a median follow-up of 13.4 months (range, 3.7–24.9 months), median survival of 4.1 months, and PFS 2.7 months.


  Conclusion Top


Reirradiation is one of the treatment options for recurrent HGGs and conformal (IMRT) can be effective treatment modality for recurrent high-grade brain tumors with only mild side effects. Although survival is better in patients with good performance status and young age.

Financial support and sponsorship

Radiation Oncology and Medical Oncology.

Conflicts of interest

There are no conflicts of interest.

 
  References Top

1.
Ostrom QT, Cioffi G, Gittleman H, Patil N, Waite K, Kruchko C, et al. CBTRUS statistical report: Primary brain and other central nervous system tumors diagnosed in the United States in 2012-2016. Neuro Oncol 2019;21:v1-100.  Back to cited text no. 1
    
2.
Lamborn KR, Yung WK, Chang SM, Wen PY, Cloughesy TF, DeAngelis LM, et al. Progression-free survival: An important end point in evaluating therapy for recurrent high-grade gliomas. Neuro Oncol 2008;10:162-70.  Back to cited text no. 2
    
3.
Wong ET, Hess KR, Gleason MJ, Jaeckle KA, Kyritsis AP, Prados MD, et al. Outcomes and prognostic factors in recurrent glioma patients enrolled onto phase II clinical trials. J Clin Oncol 1999;17:2572-8.  Back to cited text no. 3
    
4.
Bloch O, Han SJ, Cha S, Sun MZ, Aghi MK, McDermott MW, et al. Impact of extent of resection for recurrent glioblastoma on overall survival: Clinical article. J Neurosurg 2012;117:1032-8.  Back to cited text no. 4
    
5.
Chaichana KL, Zadnik P, Weingart JD, Olivi A, Gallia GL, Blakeley J, et al. Multiple resections for patients with glioblastoma: Prolonging survival. J Neurosurg 2013;118:812-20.  Back to cited text no. 5
    
6.
Ostrom QT, Bauchet L, Davis FG, Deltour I, Fisher JL, Langer CE, et al. The epidemiology of glioma in adults: A “state of the science” review. Neuro Oncol 2014;16:896-913.  Back to cited text no. 6
    
7.
Conti A, Pontoriero A, Arpa D, Siragusa C, Tomasello C, Romanelli P, et al. Efficacy and toxicity of CyberKnife re-irradiation and “dose dense” temozolomide for recurrent gliomas. Acta Neurochir (Wien) 2012;154:203-9.  Back to cited text no. 7
    
8.
Ulutin C, Fayda M, Aksu G, Cetinayak O, Kuzhan O, Ors F, et al. Primary glioblastoma multiforme in younger patients: A single-institution experience. Tumori 2006;92:407-11.  Back to cited text no. 8
    
9.
Selch MT, DeSalles AA, Solberg TD, Wallace RE, Do TM, Ford J, et al. Hypofractionated stereotactic radiotherapy for recurrent malignant gliomas. J Radiosurg 2000;3:3-12.  Back to cited text no. 9
    
10.
Dincoglan F, Beyzadeoglu M, Sager O, Demiral S, Gamsiz H, Uysal B, et al. Management of patients with recurrent glioblastoma using hypofractionated stereotactic radiotherapy. Tumori 2015;101:179-84.  Back to cited text no. 10
    
11.
Nieder C, Astner ST, Mehta MP, Grosu AL, Molls M. Improvement, clinical course, and quality of life after palliative radiotherapy for recurrent glioblastoma. Am J Clin Oncol 2008;31:300-5.  Back to cited text no. 11
    
12.
Alexander E 3rd. Glioblastoma revisited: Do clinical observations match basic science theory? Radiosurgery: Clinical observations. J Neurooncol 1993;17:167-73.  Back to cited text no. 12
    



 
 
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