INTRODUCTION

Brain tumours are a group of neoplasms which originate from different cells of the central nervous system or metastasise to the central nervous system from systemic cancers.[1] The incidence of brain tumours in India ranges from 5 to 10/100,000 population with an increasing trend.[2] Amongst them, the most prevalent type is brain metastases, occurring in around 25% of cancer patients. The ratio of metastasised to primary brain tumours is 10:1.[3] Brain tumours can present with either focal or generalised clinical signs and symptoms. Elevated intracranial pressure (ICP) is the cause of general symptoms including seizures, headache, nausea and vomiting. Compression of specialised regions or tissue destruction is the cause of focal symptoms, which include unilateral weakness, personality abnormalities, dysphasia, motor weakness and/or memory loss.[4] Hence, these patients with many different symptoms need specialised palliative care. The lack of palliative and rehabilitative treatments such as supportive care, counselling and speech therapy, as well as the high number of emergency visits and acute admissions to hospital, may cause stress amongst patients and caregivers.[5] The concept of ‘early’ palliative care has been introduced more recently to differentiate palliative interventions delivered earlier in the disease trajectory from those in the terminal phase or last days of life.[6] Palliative care is more effective when it is started early in the disease trajectory. Early palliative care, in addition to traditional therapy, has been shown to improve quality of life (QoL) of patients and their caregivers according to several experts. Furthermore, early palliative care implementation can help to provide tailored and effective care for the patient, which enhances patient comfort and meets their needs.[7] Although there were research data published for incidence of brain tumour and symptom burden in patients have brain tumours and impact of palliative whole brain radiotherapy in Indian population, there are not enough studies regarding the impact of integration of early palliative care in this type of patient population with involvement of palliative medicine specialists. Hence, we conducted this study to know the impact of early palliative care in patients having brain tumours by assessing improvement in symptom burden and overall QoL of these patients of the western Indian population.

The primary aim of our study was to assess symptom burden in brain tumour patients, and the secondary aim was to assess the impact of integration of early palliative care on it and overall QoL in these patients.

MATERIALS AND METHODS

This was a prospective analytical study conducted at the state Cancer Institute of Western India. This study was approved by the Institutional Review Committee.

After taking informed consent, 100 patients were included in this study according to the following inclusion and exclusion criteria.

Inclusion criteria

Patient with primary or secondary brain tumour diagnosed within 4 weeks

Patient with recurrent brain tumour within 4 weeks of their diagnosis

Age >18 years

Ability to understand and respond to questionnaire in Hindi, Gujarati or English language

Patients who are available to give follow-ups.

Exclusion criteria

Patients who were not willing to participate in the study

Patients with a history of drug abuse, alcohol abuse or having any psychiatric condition

Any condition as investigator’s opinion makes the patient unsuitable for study participation

Patients who were participating in another study.

Demographic data of study population such as age, gender and clinical data of study population such as diagnosis and type of palliative treatment received by patient were documented on the first visit. Symptom burden was assessed by integrated palliative care outcome scale (IPOS) and QoL was assessed by European Organisation for Research and Treatment of Cancer Quality of Life Questionnaire Brain Neoplasm 20 (EORTC–QLQ-BN-20). Translated Hindi version of IOPS and EORTC–QLQ-BN-20 tools were used wherever required after taking necessary permission. These tools were filled out on first visit and then with subsequent follow-up to 6th month either by the patient himself or by caregivers.

The IPOS tool was used to assess symptom burden and to measure impact of early palliative care in these patients by comparing data from baseline to subsequent follow-up. This tool includes 17 items divided into physical symptoms, emotional issues and communication problems. Physical symptoms include pain, shortness of breath, weakness, nausea, vomiting, poor appetite, constipation, dry mouth, drowsiness and poor mobility. Emotional issues include ‘feeling anxious or worried about illness or treatment’, ‘family or friends being anxious or worried’, ‘feeling depressed’ and ‘feeling at peace’. Communication part includes ‘being able to share feelings with family or friends’, ‘having as much information as wanted’ and ‘any practical problems being addressed or not’. All 17 items of questionnaire scores ranged from 0 (highest positive value = no symptom burden/problem) to 4 (highest negative value = overwhelming symptom burden/problems). The IPOS total score ranges from 0 to 68. Hence, the higher numbers indicate worse outcomes.[8]

The EORTC–QLQ-BN-20 was used to assess QoL in our study by comparing data of baseline with subsequent follow-up which is a validated brain specific questionnaire tool for brain tumours. This questionnaire includes 20 questions, which include four scales (Future uncertainty, visual disorders, motor dysfunction and communication deficit) and seven single items (headache, seizures, drowsiness, hair loss, itchy skin, weakness of legs and bladder control). All 20 questions rated on a 4-point response scale, ranging from ‘not at all’ to ‘very much’. Raw score was calculated for four multi-item scales and transformed all multi-item and single item scales to standardised scores from 0 to 100.[9]

Palliative care intervention

Palliative care is given according to the need of the patients and severity of symptoms, including pharmacological and non-pharmacological measures.

Headache due to raised ICP was treated with analgesics in the form of acetaminophen, non-steroidal anti-inflammatory drugs and strong opioids. Headache due to raised ICP was treated with analgesics in the form of Acetaminophen, NSAIDs and strong opioids along with steroids and osmotic diuretics. For nausea and vomiting, prokinetic agents were prescribed to take as and when required. Again, in these patients common cause is raised ICP; measures to alleviate the effect of raised ICP were taken as mentioned above. Due to restricted mobility and medications, these patients have constipation and which was managed by dietary modification and osmotic or stimulant laxatives or both. As very common presenting symptoms, seizures were managed by anti-convulsants such as levetiracetam, lacosamide or gabapentinoids or combination. We prescribed benzodiazepines for insomnia and anxiety, which also helped to control seizures.

Multiple counselling sessions and cognitive behavioural therapy were offered to the patients to deal with psychological, emotional and communication issues. We used cognitive behavioral therapy (CBT) for patient and their caregivers to address anxiety and depression, which helps identify and challenge unhelpful thoughts, to teach strategies to break negative thought patterns, to help develop coping skills and to help relieve insomnia and pain.

For affected family, we provided comprehensive approach and strategy to support them which includes information about disease status, prognosis, goal of treatment, patient’s symptoms and problems, training about optimal management of disabled patient, discussion about treatment decisions in the last phase of life and patient’s preference regarding place of death. Nutrition and hydration needs were planned in advance to avoid hospitalisation.

Statistical analysis

Continuous variables such as age, data of EORTC–QLQBN-20 and symptoms severity of IPOS were described as mean (X) ± standard deviation (SD), while categorical variables such as gender, diagnosis, treatment taken previously and different symptoms reported by patients on IPOS were described as number (frequency) and percentages. Data of EORTC–QLQ-BN-20 and IPOS reported on first visit was compared with 1st month, 3rd month and 6th month follow-up and P-value (<0.05 is considered as significant) was calculated using one-way analysis of variance (ANOVA) test. In addition to this, we also did post hoc analysis of ANOVA test using Tukey honestly significant difference (HSD) test (<0.05 is considered significant). For all this statistical analysis, we used socscistatistics.com calculator.

RESULTS

Total 100 patients enrolled in our study. Table 1 shows demographic data of all patients (Age, gender, diagnosis and treatment taken). Among the total 100 patients, 27 were of primary brain tumour and 73 of secondary brain tumour and the rest number of patients during each follow-up.

Table 1: Demographic data.

Category Findings Age (years) (Mean±SD) 45.86±10.88 Gender (n; %)   Male 48 (48)   Female 52 (52) Diagnosis (n; %)   Primary brain tumour 27 (27)   Primary lung carcinoma with brain metastasis 33 (33)   Primary breast carcinoma with brain metastasis 36 (36)   Other diagnosis with brain metastasis 4 (4) Treatment taken previously (n; %)   Only symptomatic treatment 23 (23)   Palliative radiotherapy 46 (46)   Palliative chemotherapy 31 (31) Number of patients in follow-up (n)   Baseline 100   At 1 month 96   At 3 month 54   At 6 month 34

Table 2 shows comparative data of IPOS score severity from baseline to 6th month.

Among physical symptoms, significant improvement was noted in pain, nausea, vomiting and constipation. Among emotional issues, significant improvement was noted in feeling anxious or worried about illness, family or friends feeling anxious or worried about illness and feeling at peace. For communication problems, significant improvement was noted in being able to share feelings, which had adequate information and practical issues being addressed. We also noted significant improvement in total score of IPOS. We found these significant improvements by ANOVA test and also by post hoc ANOVA test.

Table 2: Comparative data of symptoms severity of IPOS.

IPOS tool questions Baseline mean (±SD) 1st Month mean (±SD) 3rd Month mean (±SD) 6th Month mean (±SD) P-value by ANOVA test P-value by Tukey HSD test Physical symptoms 14.10±4.4 9.3±3.98 8.59±3.84 8.4±2.52 <0.0001 <0.0001   Pain 2.96±1.24 1.21±0.97 0.67±0.68 0.45±0.79 <0.001 <0.0001   Shortness of breath 0.56±0.8 0.42±0.79 0.3±0.54 0.24±0.66 0.336 0.336   Weakness 1.42±0.98 1.13±0.82 1.6±0.75 1.94±0.75 0.133 0.133   Nausea 2.13±0.77 0.96±0.82 0.48±0.51 0.61±0.59 0.001 0.001   Vomiting 2.04±0.88 0.83±0.81 0.56±0.89 0.37±0.87 0.036 0.036   Poor appetite 1.26±0.81 1.21±0.68 1.07±0.96 1.36±0.56 0.14 0.14   Constipation 1.46±1.26 1.02±0.93 1±0.92 0.26±0.36 0.043 0.043   Dry mouth 0.4±0.53 0.5±0.74 0.56±0.89 0.29±0.59 0.577 0.577   Drowsiness 0.73±0.87 0.63±0.89 0.92±0.80 1.41±0.51 0.495 0.495   Poor mobility 1.13±0.97 1.44±1.03 1.43±1.04 1.47±0.8 0.408 0.408 Emotional issues 8.48±2.26 7.96±1.90 6.26±2.7 5.29±2.82 <0.0001 <0.0001   Feeling anxious or worried about illness 2.31±0.92 2.15±0.85 1.48±0.98 1.29±0.85 <0.001 <0.0001   Family or friends feeling anxious or Worried about illness 2.9±0.9 2.6±1.05 1.93±1.24 1.65±1.41 <0.001 <0.0001   Felling depressed 1.23±0.9 1.46±0.5 1.26±0.94 1±0.87 0.196 <0.0001   Not felling at peace 2.04±1.12 1.75±0.84 1.59±0.84 1.35±0.93 0.031 <0.0001 Communication problems 5.63±1.63 5.06±1.21 4.96±1.66 3.12±1.32 <0.0001 <0.0001   Not able to share feeling with family or friends 1.94±0.78 1.91±0.65 1.74±0.9 1.12±86 0.001 <0.0001   Had no adequate information as wanted 1.92±0.88 1.73±0.71 1.63±0.84 1.06±0.75 0.001 <0.0001   Practical issue been not addressed 1.77±0.78 1.46±0.65 1.59±0.8 0.94±0.56 <0.001 <0.0001 Total 28.51±5.59 22.35±4.18 19.81±5.84 16.81±4.58 <0.0001 <0.0001

Table 3 shows the frequency of clinically relevant symptoms reported by patients during baseline to 6th month follow-up among 17 IPOS items described in percentage. ‘Family or friends feeling anxious or worried about illness’ was the most frequent issue reported at baseline in 100% patients. On 1st month follow-up, ‘Not able to share feeling with family or friends’ was the most frequently reported issue in 95.83% patients. ‘Weakness’ was most frequently reported symptom at 3rd month follow-up in 85.18% patients. On 6th month follow-up, the most frequent reported symptom was ‘poor mobility’ in 88.23% patients.

Table 3: Frequency of symptoms reported by IPOS.

IPOS tool questions Baseline (%) 1st Month (%) 3rd Month (%) 6th Month (%) Pain 80.76 70.83 55.55 52.94 Shortness of breath 34.61 31.25 25.92 11.76 Weakness 82.69 77.08 85.18 76.47 Nausea 82.69 70.83 48.14 23.52 Vomiting 73.07 62.5 33.33 29.41 Poor appetite 84.61 85.41 70.37 76.47 Constipation 75 66.66 62.96 70.58 Dry mouth 38.46 35.41 37.03 23.52 Drowsiness 51.92 41.66 37.03 82.35 Poor mobility 76.92 81.25 70.37 88.23 Feeling anxious or worried about illness 98.07 79.16 74.07 58.82 Family or friends feeling anxious or Worried about illness 100 81.25 70.37 52.94 Felling depressed 90.38 75 48.14 29.41 Not feeling at peace 88.46 81.25 37.03 23.52 Not able to share feeling with family or friends 96.15 95.83 48.14 47.05 Had no adequate information as wanted 90.38 66.66 40.74 23.52 Practical issue been not addressed 94.23 87.5 37.03 29.41

Table 4 shows mean (SD) of single and multi-item scores of EORTC–QLQ-BN-20 from baseline to 6th month follow-up. Among all these brain neoplasm 20 QoL domains, significant improvement was noted in future uncertainty, headache, seizures, bothering due to hair loss and bothering due to itchy skin from baseline to 6th month in ANOVA test and also in post hoc ANOVA. For the rest of the scores, there was no improvement.

Table 4: Comparative data of single and multi-item scores of EORTC-QLQ-BN-20.

EORTC–QLQ-BN-20 questions Baseline mean (±SD) 1st Month mean (±SD) 3rd Month mean (±SD) 6th Month mean (SD) P-value by ANOVA test P-value by Tukey HSD test Future uncertainty 39.42±16.67 31.15±19.60 27.87±22.16 19.62±26.27 0.042 0.042 Visual disorders 11.96±16.67 12.75±21.16 13.17±21.95 24.18±29.98 0.242 0.242 Motor dysfunction 28.84±24.43 25.69±20.39 25.51±20.81 32.02±23.53 0.703 0.703 Communication deficit 26.49±15.58 26.15±16.45 23.87±16.82 33.33±20.03 0.317 0.317 Headache 42.95±33.23 22.35±28.53 9.88±15.33 3.92±11.07 0.0001 <0.0001 Seizures 28.20±30.52 18.5±28.3 3.70±10.50 5.88±13.10 0.0002 <0.0001 Drowsiness 12.18±17.50 13.89±20.43 13.64±21.52 17.84±14.57 0.092 0.56 Bothering due to hair loss 18.97±14.93 15.72±18.14 12.88±13.82 7.84±12.14 0.021 0.021 Bothering due to itchy skin 28.33±16 10.42±18.39 11.11±2.39 7.84±18.74 0.023 0.023 Weakness of legs 33.33±28 31.25±26.99 32.10±28.58 37.25±37.05 0.902 0.902 Bladder control 21.15±26.43 24.3±28.10 23.45±25.74 25.49±34.40 0.925 0.925 DISCUSSION

Palliative care includes managing symptoms and offering assistance to patients and carers at every stage of life-from first referral to end-of-life care and during bereavement. Palliative care aims to enhance the patient’s QoL by a multidisciplinary approach to help the patient live as actively as possible and neither hastening nor postponing death.[10]

Yamanaka et al. and Chow et al. evaluated patients with brain metastasis and found a significant symptom burden. They commonly found headache, general fatigue, drowsiness, mood disturbance, seizure, disturbed sleep, difficulty in remembering and cognitive dysfunction. They found some symptoms have been secondary to treatment (hair loss, itching from radiation therapy and weakness of the legs from corticosteroids), and some were probably non-specific for brain cancer (uncertainty about the future and pain), but others are probably due to the primary disease.[11,12]

Armstrong et al. studied the symptom burden in patients with primary brain tumours. They found that more than 50% of patients had at least ten concurrent symptoms, and 40% of patients reported at least three symptoms with moderate-to-severe severity. Fatigue, disturbed sleep, headache, difficulty remembering and distress were the most severe symptoms reported by all tumour grades.[13] Similarly, in our study, the most common distressing symptoms with variable severity and frequency were nausea, vomiting, weakness, pain and poor mobility. While some of these symptoms are seen in patients with other malignancies, headache, neurological deficits, fatigue and cognitive dysfunction, and seizure are specifically encountered in patients with brain tumours. Neurological symptoms in patients with brain tumour are mainly associated with increased ICP, which may alter the QoL of patients and require palliative care intervention such as symptom management, psychological, and sociological care of patients and caregivers.

The physical symptoms and functional impairment of brain tumour may result in more specific neuropsychiatric and behavioural manifestations. Especially, anxiety and depression are commonly noted in brain tumour patients. Liu et al. studied QoL in patients with brain tumours and showed mixed findings, with considerable anxiety in 29– 60% of cases and depression in 7.9–90% of cases. This has also shown an adverse impact on survival and is one of the most important independent predictors of QoL.[14] Anxiety may result from situational stress related to diagnosis and prognosis or may be directly related to the consequences of the tumour.[15] As per IPOS, in our study, 98.07% of patients and 100% of caregivers are anxious or worried about their illness. However, on subsequent follow-up, it was significantly reduced to 58.8% and 52.9%, respectively. It may be due to palliative intervention such as managing physical symptoms and addressing psychological, emotional or communication issues with repeated counselling. Similar results found in other studies suggest that psychological symptoms like anxiety were associated with higher symptom burden, and palliative care intervention can reduce it significantly.[16,17]

When compared to other systemic malignancies, caregivers of brain tumour patients typically experience higher levels of distress and exhaustion. We found in our study, as per IPOS, 100% of caregivers had anxiety and worries about their patient’s illness. Neurologic impairments are extremely distressing, especially cognitive dysfunction, communication difficulties, mood swings and personality changes have a negative impact on caregivers’ well-being. Many day-to-day nursing care and psychosocial issues of patients were not addressed in routine oncological treatment. Dave et al. found that providing information and training about nursing care issues of cancer patients to caregivers helps to improve their knowledge, attitude and practice significantly. This may be potentially beneficial in taking better care of their patients.[18] In our study, patients had many unaddressed practical and communication issues which were addressed by a palliative care physician, like providing detailed information in a stepwise manner starting from the early phase of diagnosis, followed by preparing patients and caregivers for future transitions of care.

Fatigue and drowsiness are the most concerning symptoms in patients with brain tumours affecting their QoL than those with other tumours. Studies of Slotman et al. and Wong et al. found deterioration in domains of fatigue and drowsiness during subsequent follow-up.[19,20] Our findings are comparable with their results. QoL in brain tumour patients is a subjective evaluation which involves a person’s multi-dimensional well-being in terms of functional or physical status, cognitive function, as well as social and emotional well-being. There are many determinants of physical, cognitive, emotional, and social functioning which are influenced by the patients’ social environment, severity of physical symptoms, general health, spirituality, coping and existentiality. QoL scores are also affected by tumour location in the brain and treatment received.[21] The score of headache, seizure and bothering due to itchy skin and hair loss were significantly improved in subsequent follow-up, while motor dysfunction, communication deficit, visual disorders and weakness of legs deteriorated, which are comparable with the study of Diana Steinmann.[22] They reported that 3 months after the start of radiotherapy, QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs. They reported that three months after the starting of radiotherapy, QoL deteriorated significantly in the areas of global QoL, physical function, fatigue, nausea, pain, appetite loss, hair loss, drowsiness, motor dysfunction, communication deficit and weakness of legs, although the score for headaches remained stable.[22] In our study, some domains of QoL were improved in subsequent follow-ups, while some domains deteriorated as reported in EORTC–QLQ-BN-20.

The improvement of headache and other domains might be due to early involvement of palliative physician, while deterioration in some domains of QoL may be due to intracranial and extracranial progression of disease or adverse treatment effects. As disease progresses, neuro-cognitive deficit may become irreversible, and even these minor deficits can affect health-related QoL and functional independence. Early integration of palliative care into the treatment schedule can help patients and their caregivers to live good QoL as much as possible.

Strengths of study

As there are not enough studies regarding the impact of integration of early palliative care in patients with brain tumours. Therefore, this study will provide insight for further multicentre studies and also provide evidence for the requirement of early integration of palliative care in this speciality.

Limitation of study

Limitation of this study is that it single-centre study with a small sample size. There is a need for a multicentre study with a large sample size to strengthen reliability and validity. There may be attrition bias.

CONCLUSION

We conclude that brain tumour patients are suffering from various distressing symptoms. Early involvement of palliative care specialists with neuro-oncology treatment can help in better management of various physical and psycho-social symptoms, which lead to better QoL of patients and their caregivers.