Long term palliation of a metastatic primary gliosarcoma with stereotactic body radiotherapy

Primary gliosarcoma (PGS) is rare and is known for extra cranial metastases. The overall outcome is dismal and hence the focus is on providing the best quality of life. This report describes a seventy-year-old lady who at presentation had metastatic primary gliosarcoma with intractable cough. Her lung lesion was treated with stereotactic body radiotherapy (SBRT) to a dose of 10 Gy per fraction for three consecutive days. She was free of cough till her death at eighteen months after treatment. This is probably the first reported case of excellent long-term quality of life in a patient of metastatic primary gliosarcoma.


Introduction
Gliosarcoma (GS) constitutes 1.8-2.8% of all glioblastoma multiforme (GBM). 1 It can be primary when it occurs "de novo" as opposed to secondary when initially the patient was treated as glioma and subsequently the recurrence reveals gliosarcoma. 2 In addition to histologically resembling GBM, it also shows mesenchymal component which resembles fibroblast, cartilage, bone, smooth muscle, striated muscle or adipose tissue. 3 Due to the sarcomatous component, they are prone for extracranial metastasis, most common sites being liver, lung and bone. 4 The mesenchymal element is the reason for its poor prognosis compared to GBM. The treatment is same as that of GBM which includes maximum safe resection followed by adjuvant radiation and temozolamide. 5 From a single institute in India, Kumar et al. 6 conducted an audit of 24 patients and found that the overall survival was similar, 7.3 and 7.5 Months with GS and GBM respectively. Maximum time to disease progression is 11 months and longest survival described in the literature is 18 months. 5 Majority of the times, the emphasis is on the cancer directed therapy and relatively less importance is given to the worsening symptoms. Also the therapy itself has its own acute sequelae that may add to the already compromised quality of life. Hence, it is very important to employ treatments that are more effective and least toxic. Hypo fractionation with stereotactic body radiotherapy (SBRT) delivers high dose in short time with minimal toxicity. This is an attempt to present a case report of a metastatic primary gliosarcoma who had complete relief from cough until her death.

Methods and Materials
A 73-year-old lady presented with weakness of right hand of 20 days duration. She was diabetic since last ten years, hypertensive since one year and asthmatic for past five years and was on regular medication. She was investigated with magnetic resonance imaging (MRI) and underwent gross total excision of a space-occupying lesion arising from the left parietal region. The postoperative histopathology was grade IV Gliosarcoma.
Patient was taken up for adjuvant radiation 40 Gy/20 fraction with 3-dimensional conformal radiotherapy technique (3DCRT) along with temozolamide. Patient had persistent cough and hence a chest x-ray was done which revealed a lesion in the midzone of right lung. The cough was persistent and the patient was not able to sleep which severely compromised her quality of life. Patient was subsequently taken up for SBRT, boost to the tumor bed and palliative radiation to the lung lesion. The planning positron emission tomography (PET) scan picked up additional lesions in the left gluteal region and right upper thigh, both were asymptomatic and hence kept under observation.

Stereotactic body radiotherapy
Three gold fiducials were placed in and around the lung lesion and radiotherapy planning was done seven days later. Patient was immobilized with orifit cast for the head and vacloc for the lung treatment. Simulation was done using computerized tomography (CT), MRI as well as PET scan. Images of CT /MR were fused for contouring brain lesion and CT/PET images were used to contour lung lesion. PET detected lung lesion was contoured as gross tumour volume. Spinal cord, lungs, heart, great vessels, esophagus and tracheobronchial tree were contoured as organs at risk. A plan was generated on multi plan treatment planning system (TPS) using ray tracing algorithm. The dose received by the tumour as well as normal structures (Figure 1) was evaluated qualitatively in axial, coronal and sagittal sections (Figure 2-4) and quantitatively using dose volume histograms (Figure 5). Patient was treated to a dose of 10 Gy per fraction prescribed at 82%, for consecutive three days. A total of 247 beams were used at 87 different nodal stations as shown (Figure 6). Intrafraction verification was done tracking the fiducials and synchrony system was used to monitor respiration. Patient had severe cough during the first fraction, the treatment had to be interrupted many times and hence took a longer time. However, subsequent fractions were uneventful. Patient also received boost dose of radiation to the brain lesion to a dose of 12 Gy in two fractions.

Results and Discussion
She was on regular follow up and had complete relief from cough. PET scan done six months later showed reduction in lung lesion size, however the soft tissue lesions had increased in size but patient still remained asymptomatic. She was alive for 18 months after diagnosis when she died of myocardial infarction and was completely free of cough until her death.
Quality of life is the most important aspect of a metastatic disease. The emphasis to achieve this is on employing treatment modalities that are highly effective and at the same time less toxic for the patient. SBRT is one such radiation technique wherein multiple beams from different angles are used to focus on a particular point. Thus, it deposits maximum dose around that point and the surrounding normal structures get minimal dose, reducing the rate of complications. This is classically used in small tumours less than three cms, relatively radio resistant tumours, which require higher doses, and those tumours that are situated near critical structures. Our patient typically had all these factors and hence was treated with SBRT. To our knowledge, this report is the first of its kind, which demonstrates long-term palliation of cough and is gratifying not only to the patient but also to the palliative caregivers.

Conclusion
Primary gliosarcoma is an aggressive tumour and is associated with a poor outcome. Cough as a symptom of metastatic cancer is very difficult to treat and reduces the quality of life of a terminally ill patient. Selected patients do have long-term palliation from SBRT which has the advantage of higher dose delivery over shorter duration of treatment and also is not associated with any complications.