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 Table of Contents  
ORIGINAL ARTICLE
Year : 2021  |  Volume : 12  |  Issue : 2  |  Page : 53-58

Clinical-radiological prognostic factors in patients with brain metastasis-A retrospective study from a tertiary care centre In Easten India


Department of Radiation Oncology, RIMS, Ranchi, Jharkhand, India

Date of Submission01-Feb-2021
Date of Acceptance15-Feb-2021
Date of Web Publication07-May-2021

Correspondence Address:
Dr. Rashmi Singh
Department of Radiation Oncology, RIMS, Ranchi, Jharkhand
India
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/jrcr.jrcr_4_21

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  Abstract 


Background: Brain metastasis (BM) is the most common (MC) intracranial tumor in adults. The outcome depends upon prognostic factors (PF) and optimal use of multimodality treatment. Objectives: We aimed to know clinicoradiological PF and their correlation in BM patients. Materials and Methods: Retrospectively, 19 BM patients treated with radiotherapy (RT) for the same between January 2018 and December 2019 were selected. Details of age, sex, Karnofsky performance status (KPS), recursive partitioning analysis (RPA), primary diagnosis, histopathology report, imaging details for BM-number, size and location, extracranial metastasis (EM), and primary tumor control (PTC) status were collected from the physical records. Descriptive statistics for the categorical variables and Bi-variate Spearman correlation were used to analyze the correlation between BM size, number, type of primary (TOP) with RPA, KPS, age, gender, PTC, and EM individually using the SPSS software version 20. Results: 84.2% of patients were <65 years age and 57.8% were males. Lung cancer was the MC primary (73.7%). The PF in majority were KPS <70 (52.6%), RPA III (52.63%), multiple BM lesions (73.7%), uncontrolled primary (78.9%), and BM size >1.5 cm (84.2%). EM was observed in 31.6% patients. 94.73% and 68.4% of patients received whole-brain RT and systemic treatment, respectively. The maximum duration of FU was 12 months and 78.9% of patients were lost to FU post-RT. Significant correlation was observed between BM size and RPA class, KPS (R = 0.456; P = 0.049), and TOP correlated with gender (P = 0.028) and PTC (P = 0.000). However, no significant correlation between the age, RT dose, EM, number of lesions and RPA, PS (P = 0.339). Conclusions: The presence of multiple poor PF in majority of our patients and their poor follow-up indicate inertness toward health issues. Furthermore, larger BM lesions correlated with higher RPA suggesting poor outcome, so treatment modality to be judicially selected. The positive correlation between gender, PTC and primary cancer, and their prognostic role in BM should be validated in the larger studies.

Keywords: Brain metastasis, clinical, outcome, prognostic factors, radiological


How to cite this article:
Singh R, Kumar A, S Munda PK, Tudu R, Raina P. Clinical-radiological prognostic factors in patients with brain metastasis-A retrospective study from a tertiary care centre In Easten India. J Radiat Cancer Res 2021;12:53-8

How to cite this URL:
Singh R, Kumar A, S Munda PK, Tudu R, Raina P. Clinical-radiological prognostic factors in patients with brain metastasis-A retrospective study from a tertiary care centre In Easten India. J Radiat Cancer Res [serial online] 2021 [cited 2021 Sep 22];12:53-8. Available from: https://www.journalrcr.org/text.asp?2021/12/2/53/315667




  Introduction Top


Brain metastasis (BM) is the most common (MC) intracranial tumor in adults. An estimated 20%–40% of cancer patients develop BM during their life time.[1] In the USA, every year 200,000 new cases of brain metastasis are detected.[2] Lung cancer is approximately solely responsible for 40%–50% cases with BM, the other common ones are breast cancer (15%–25%), melanoma (5%–20%), and renal cell cancer (5%–10%).[2] The contrast-enhanced magnetic resonance imaging (MRI) brain is the gold standard[3] for the diagnosis of BM as a computed tomography (CT) scan can miss small lesions or tumors in the posterior fossa and also positron emission tomography (PET) scan has a sensitivity of only 75% and specificity of 83%.

Treatment options for BM include whole-brain radiotherapy (WBRT), stereotactic radiosurgery/stereotactic body radiotherapy (SRS/SBRT), surgery, and palliative chemotherapy.

Radiotherapy

WBRT has been reported to be associated with cognitive decline. Especially in a good prognosis patients with better survival, the use of concurrent and adjuvant use of neuroprotective agents such as Memantine (N-methyl-D-aspartate) along with WBRT,[4] hippocampal sparing,[5] and deferring the WBRT with alternate options of SRS/SBRT where feasible and upfront use of central nervous system (CNS) active systemic therapy should be practiced. However, survival and local control are similar to both WBRT and SRS.[6] WBRT dose prescription varies from 20 Gy/5# to 30 Gy/10#.[7],[8] Furthermore, upfront chemotherapy instead of SRS or WBRT has been recommended in some of the asymptomatic metastasis. However, close CNS surveillance with MRI is a must, so that early intervention can be done when required.

Surgery

Single or 1–3 metastatic lesions of <3 cm in size with an overall good prognosis can be considered for the excision. Combined modality treatment has been advocated as per the promising results in different trials.[9],[10] As with excision alone, there is a 50% risk of recurrence.

Chemotherapy

Melanoma,[11],[12] non-small cell lung carcinoma,[13],[14],[15] and breast cancer[16] are some of the cancers where systemic therapy has been found to be active for BM using Nivolumab/Iplimumab, Dabrafenib, Alectinib/Crizotinib, Osimertinib, and Lapatinib, respectively, with varying response rates of 30%–50%.

Without treatment, the median survival of patients is 1 month and with steroid treatment only, median survival approximates 2 months.[17] The 1-year survival is approximately 10% with multi-modality treatment.[18]

Outcome depends on the prognostic factors (PF) and best possible management case to case basis. The Poor PF in patients with BM are poor performance status (PS), advanced age, uncontrolled primary, multiple lesions in the brain, a larger volume of the metastatic lesions, and other site metastasis. There are three prognostic groups based on recursive partitioning analysis (RPA) taking into consideration age, PS, and status of extra-cranial metastasis (EM) as advocated by the Radiation Therapy Oncology Group. The best survival was seen in RPA class I, which had a median survival of 7.1 months. Patients with Karnofsky Performance Score (KPS) <70 i.e., RPA class III had a median survival of <3 months.[19]

Ours is a Government-based tertiary care hospital in Eastern India with a Radiotherapy (RT) facility with one 6 MV Linear accelerator (LINAC) functional for nearly the last 4.5 years. Many of our patients are from poor socioeconomic status and rural areas. As it is a new center, the total number of patients treated with RT was 560 in the last 2 years. We documented 25/560 (4.4%) cases of BM in 2 years who were treated with RT at our center. As already known, BM prognosis is determined by RPA class. We aimed to study clinical and radiological PF in our patients with BM. We also tried to find the correlation between the number of brain metastatic lesions, brain metastatic tumor size, type of primary (TOP) with RPA, KPS, age, sex, primary controlled, and EM individually. This can help us in guiding/planning the diagnosis, prevention, and management of population and patients.


  Materials and Methods Top


General study details

This retrospective study conducted at our tertiary care center in the department of radiation oncology. As it is a retrospective study, written informed consent and ethical committee clearance were exempted. The study was conducted in accordance with the ethical guidelines as outlined in the declaration of Helsinki's and ICMR guidelines. There is no funding for the study.

Study participants

Patients treated with RT at our center for BM from January 2018 to December 2019 were included for the analysis. Patients' files with incomplete details and RT defaulters were excluded for this study.

Study variables

Our primary aim was to look for various clinicoradiological PF and correlation among those factors the median time to BM diagnosis since primary diagnosis and median follow-up post-RT were observed.

Study methodology

Clinical and radiological details of BM patients treated with RT for BM between January 2018 and December 2019 from the physical record stored in the department were compiled (Schema 1). Patients' details of age, sex, KPS, RPA, primary diagnosis, and histopathology report as available were noted in the case pro forma. The type of imaging studies for BM, no of metastatic lesions, their size, and their location in the brain were noted. Furthermore, the status of EM disease and control status of primary cancer were documented.

Treatment modalities

Details of treatment, including chemotherapy, surgery, or RT to brain were documented. Medical management of increased intracranial tension before or during RT was done using Tab/Inj Dexamethasone 16–24 mg/day, Mannitol, or glycerol as required. Anti-epileptics were prescribed if patients had a history of seizures or as per the standard protocol. Craniotomy and surgical excision of the lesion were done in one case. Patients received either chemotherapy/immunotherapy depending on their histological diagnosis of the primary. For WBRT, portal planning patients were treated in the supine position with an orfit cast for head immobilization on 6 MV LINAC. Parallel opposed lateral fields are used with the gantry at 90° and 270°. The field borders are kept 2 cm beyond the bony skeleton in the superior, anterior, and posterior margin, and between C1 and C2 vertebral bodies in the inferior margin. Custom blocks can be designed to avoid radiation to the eye, oral cavity, and facial structures; however, these were not made for our patients [Figure 1].
Figure 1: Whole-brain radiotherapy simulation film (Figure courtsey -Google)

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Study statistics

We included all patients as per the inclusion and exclusion criteria. There was no formal sample size calculation. Statistical analysis was done using the SPSS software version 20 IBM SPSS statistics for Windows, version 20 (IBM corp; Armonk, N. Y, USA). The categorical variables were described as frequency or percentages mean/median using the descriptive statistics. Bi-variate correlation using Spearman correlation between different PF was used in the analysis to correlate between the number of brain metastatic lesions, brain metastatic tumor size, TOP with RPA, KPS, age, sex, primary controlled, time to presentation, and EM individually.


  Results Top


Schema of the study (1)



The median age of the patient was 48 years (30–70 years). Majority of the patients were <65 years (84.2%) and males outnumbered females (57.8% vs. 42.10%). 42.1% of patients had BM as the initial presentation and the median duration for developing BM after the diagnosis of having cancer was 9 months (0–96 months).

Primary lung cancer was the MC cancer (73.7%) [Table 1] and also accounted for 50% cases in females. 68.42% of the patients were smokers. Among females, 62.5% of patients were smokers.
Table 1: Primary and histopathological diagnosis and various prognostic factors

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Histopathological diagnosis from the primary site was made by either FNAC or biopsy. The biopsy and FNA reports were available in 36.8% and 57.9% cases, respectively. In one case, excision of a single space-occupying lesion in the brain was done, considering it to be a primary brain tumor; however, the histopathological report showed it to be a metastatic adenocarcinoma. The MC histopathological diagnosis was adenocarcinoma in 68.4% of cases [Table 1].

KPS of ≥70 and <70 were observed in 47.4% and 52.6% of patients, respectively [Table 1]. The majority (52.63%) of our patients were in RPA Class III followed by Class II (47.4%).

Symptoms of increased intracranial pressure, i.e., headache, nausea, and vomiting were present in 31.57% of patients. 21.05% of patients were having altered sensorium at presentation. 47.36% of patients had to present multiple complaints as hemiparesis, headache, and nausea.

MRI, CT scan of the brain, and PET-CT were done in 42.1%, 31.6%, and 10.1% of patients, respectively. 15.8% of patients had more than one imaging for BM diagnosis. 73.7% patients had multiple lesions in the brain with a median size of 4 cm. The cerebrum was the MC site of metastasis (63.2%), with both cerebrum and cerebellum in 31.6% and 1 case had lesion located in Pons.

84.2% (16) patients had tumor size >1.5 cm on imaging, whereas 3 (15.8%) patients had ≤1.5 cm tumor size. Another factor accounting for poor survival was the multiple metastatic lesions in 73.7% of patients. EM was observed in 31.6% (6) patients. Primary tumor was controlled in only 4 (21.1%) patients, whereas majority (15/78.9%) had uncontrolled primary cancer [Table 1].

84.2% of patients received RT by WBRT using 20 GY/5#, two patients by 8 Gy/1# to WB, and intensity-modulated RT to the postoperative cavity in one patient as decided by the radiation oncologist [Table 1].

68.4% (13) patients received either chemotherapy/immunotherapy depending on their histological diagnosis of the primary. Six (31.6%) patients remained naïve to any form of chemotherapy/immunotherapy. 38.16% (5/13) patients received Gefitinib as immunotherapy with primary as lung cancer. Their EGFR status was mutation-positive (1), negative (1), and unknown in three patients. Other regimens that our patients received were Etoposide + Platinum, Sorafenib, Gemcitabine, and CAPEOX as per their primary malignancy.

15/19 (78.9%) of patients were lost to FU post-RT. They did not turn up even once post-RT. The maximum duration of FU was 12 months.

On Spearman-correlation, we observed significant correlation between BM tumor size and RPA class; and KPS (R = 0.456; P = 0.049). However, the number of lesions, i.e., single versus multiple lesions were not related with the RPA, PS (P = 0.339). Gender of the patients correlated with primary cancer type (R = 0.538; P = 0.028). Furthermore, TOP cancer correlated with controlled status of the same (R = 0.791; P = 0.000). Age, RT dose schedules, and EM did not show any correlation with other PF.


  Discussion Top


In our patients also, lung cancer was the foremost etiology and adenocarcinoma as the MC histopathology. Majority of the patients were younger than 65 years (84.2%), in RPA Class III (52.63%), and presenting with BM as the initial presentation (57.14%), BM tumor size >1.5 cm (84.2%), multiple metastatic lesions (73.7%), and uncontrolled primary (78.9%). However, EM was observed in 6 (31.6%) patients. Survival analysis was not attempted in our analysis as 15/19 patients defaulted immediately after the completion of scheduled RT. Hence, correlation study was done among different clinical-radiological factors in the pretext of available literature.

On Spearman-correlation, we observed significant correlation between BM tumor size and RPA class, and KPS (P = 0.049), gender and primary cancer type (P = 0.028), and primary cancer and controlled status of the same (P = 0.000). However, the number of lesions was not related with the RPA, PS (P = 0.339). Furthermore, age, RT dose schedules, and EM did not show any correlation with other PF.

As BM size and no of metastatic lesions are determinants for choice of surgery, SBRT, and WBRT. Furthermore, possibly this can guide for treatment selection for optimal outcome suggesting larger lesions with higher RPA may have poor outcome. However, in the present study, the number of brain lesions had no association with RPA or any other factor.

If multimodality in the form of surgery, chemo/immunotherapy and RT is used where applicable, optimum result is feasible as we observed 12 months of follow-up post-RT in one patient. Ekici et al. also have reported better median survival of patients treated with combination of surgery and WBRT than WBRT alone 13.5 m versus 5.5 months (P = 0.000).[20]

Lock et al. concluded in their study poor PS and number of metastatic sites were useful predictors of early death using a predictive model in such patients.[21]

In a study by Suteu et al., age, gender, KPS, number of BM, control of primary, presence of EM, and TOP tumor all these were the independent predictors for O.[22] However, we did not find any association between KPS/RPA and age, gender, EM, and TOP tumor.

Limitation of our study

It is a retrospective study with small patient population with no feasibility of survival analysis. Nonavailability of PET-CT for staging and response evaluation can bar patients from undergoing surgery as treatment modality for metastatic lesions. Furthermore, currently, there is no facility for Stereotactic RT/SRS at our center. Hence, all five patients with a single metastatic lesion at the brain were treated with WBRT. However, these patients were having a stable disease or uncontrolled disease at the primary site.


  Conclusions Top


The presence of multiple poor PF in majority of our patients and their poor follow-up indicate inertness toward health issues. Hence, this issue should be addressed and awareness should be increased, other causative factors should also be sought. Furthermore, larger BM lesions correlated with higher RPA suggesting poor outcome, so treatment modality to be judicially selected. The positive correlation between gender, PTC and primary cancer, and their prognostic role in BM should be validated in the larger studies.

Acknowledgment

We acknowledge all authors and all staffs of Radiation Oncology department for their support in this study.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

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