|Year : 2020 | Volume
| Issue : 1 | Page : 97-99
Neurological deterioration in a patient with lung cancer and brain metastasis
Ravi Krishna Madala1, Rahul Krishnatry2, Vanita Noronha1, Vijay Patil1, Amit Joshi1, Nandini Menon1, Hemanth Muthuluri1, Kumar Prabhash1
1 Department of Medical Oncology, Tata Memorial Center, Tata Memorial Hospital; Homi Bhabha National Institute, Mumbai, Maharashtra, India
2 Homi Bhabha National Institute; Department of Radiation Oncology, Tata Memorial Center, Tata Memorial Hospital, Mumbai, Maharashtra, India
|Date of Submission||30-Dec-2020|
|Date of Decision||12-Jan-2020|
|Date of Acceptance||13-Jan-2020|
|Date of Web Publication||24-Feb-2020|
Department of Radiation Oncology, Tata Memorial Center, Homi Bhabha National Institute, Mumbai, Maharashtra
Source of Support: None, Conflict of Interest: None
|How to cite this article:|
Madala RK, Krishnatry R, Noronha V, Patil V, Joshi A, Menon N, Muthuluri H, Prabhash K. Neurological deterioration in a patient with lung cancer and brain metastasis. Cancer Res Stat Treat 2020;3:97-9
|How to cite this URL:|
Madala RK, Krishnatry R, Noronha V, Patil V, Joshi A, Menon N, Muthuluri H, Prabhash K. Neurological deterioration in a patient with lung cancer and brain metastasis. Cancer Res Stat Treat [serial online] 2020 [cited 2020 Apr 7];3:97-9. Available from: http://www.crstonline.com/text.asp?2020/3/1/97/279066
| Case History and Approach|| |
A 52-year-old male, known tobacco chewer for 15 years, with no comorbidities was evaluated for complaints of breathlessness on exertion and found to have left lower lobe mass lesion with bilateral pleural effusion and mediastinal and right supraclavicular lymphadenopathy. Pleural fluid cytology and biopsy from the right supraclavicular lymph node revealed adenocarcinoma with epidermal growth factor receptor (EGFR) exon 19 deletion positive. He was diagnosed with cT2N3M1a adenocarcinoma of the lung, Stage IVA as per the American Joint Committee on Cancer, 8th edition. He was treated on a clinical trial and received gefitinib with chemotherapy, consisting of four cycles of 3-weekly pemetrexed and carboplatin, followed by 11 cycles of maintenance pemetrexed with sustained partial response. Post 11 cycles, he developed a headache and was found to have a brain metastasis in the right occipital region [Figure 1]a and [Figure 1]b. He was treated with whole-brain radiotherapy (WBRT) at a dose of 20 Gy in five fractions, 4 Gy per fraction in November 2018. Since he had progressed only in the brain and had stable disease extracranially, he continued on maintenance pemetrexed along with gefitinib, with the last cycle (cycle 21) administered on August 1, 2019.
|Figure 1: Preradiotherapy magnetic resonance images with T2 plain axial (a) showing T2 dark hypointense lesion (black arrow) in right parieto-occipital region with disproportionate edema (black star), the same lesion is seen as enhancing hyperintense mass (black arrow) in T1 contrast corresponding sequence (b)|
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On August 7, 2019, he presented with complaints of headache, difficulty in walking, and a seizure episode for which he was evaluated with magnetic resonance imaging (MRI) brain which showed a heterogeneously enhancing lesion in the right occipital lobe and surrounding white matter edema with postcontrast enhancement [Figure 2]a and [Figure 2]b. He was started on steroids and antiepileptics, in spite of which he continued to have recurrent seizures.
|Figure 2: Postradiotherapy magnetic resonance images with T2 plain axial (a) showing disproportionate edema with posttreatment changes (black arrow) with enhancement locally in the right parieto-occipital region in corresponding image sequence with T1 contrast (black arrow) “cut green pepper appearance” (b)|
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What is the diagnosis? Once you have finalized your answer, please read on.
| Discussion|| |
Twenty-five percent of patients with advanced non-small cell lung cancer develop brain metastasis, and the incidence continues to rise. Disease progression in the form of brain metastasis occurs in approximately one-third of the patients with EGFR mutation during treatment. Surgery and/or radiotherapy (RT) form the cornerstone of the current management of brain metastasis. RT can be either in the form of WBRT or stereotactic radiosurgery (SRS) or the combination of both. WBRT or SRS leads to a similar overall survival (OS) benefit; WBRT is associated with lower brain progression rates but a higher negative impact on neurocognitive outcomes. WBRT prolongs the OS of patients with brain metastases from 3 to 5 months., Surgical resection followed by WBRT is associated with an improvement in OS to 40 weeks, when compared to patients who undergo biopsy followed by WBRT in whom the median OS is 15 weeks, relative risk of death 2.2, P < 0.01.
One of the feared complications of brain RT is the development of radiation necrosis. It is more commonly described associated with SRS than conventional WBRT, with variable incidences in reports ranging from 5% to 24% depending on various factors. These factors include dose–volume relation, prior RT treatment, the use of concurrent chemotherapy or targeted agents, location, volume of normal brain irradiated as clinical target volume or planning target volume, intrinsic radiosensitivity of a patient, and the criteria for diagnosis to name a few. The exact etiology of radiation necrosis is poorly understood and is believed to be due to either direct vascular injury or glial injury; both mechanisms finally lead to the upregulation of local inflammatory response, ischemia, and expression of vascular epidermal growth factor (VEGF) causing increased leakage and accumulation of fluid into the extracellular space resulting in cerebral edema.,
It is of paramount importance to differentiate radiation necrosis from progressive or recurrent disease. Although histology is considered the gold standard for diagnosis, this is rarely obtained due to the risk of complications. The critical diagnosis depends on noninvasive diagnostic modalities. The most common radiological investigation used is used is MRI demonstrating some degree of contrast enhancement and perilesional edema. However, these classical features considerably overlap with tumor progression. At times, the clinical picture is also overlapping. The dogma of temporal changes (i.e., increase in size over time) is again not specific to either entity., There are certain enhancement patterns described in the literature as 'Swiss cheese,' 'soap bubble,' or 'cut green pepper' [Figure 2]b, initially thought to favor radiation necrosis, but these have only a 25% positive predictive value. The MRI of our patient showed successful use of conventional MR for diagnosing and treating radiation necrosis that developed in the background of a large metastasis treated with WBRT and concurrent systemic agents. It showed a contrast-enhanced lesion in the right parieto-occipital lobe [Figure 2]b with surrounding white matter edema [Figure 2]a, showing decreased, ill-defined gyriform postcontrast enhancement which represented post-RT necrosis rather than recurrence.
Other modern modalities which are useful in differentiating radiation necrosis from tumor progression are perfusion- weighted imaging and MR spectroscopy. The percentage of signal recovery more than 76% in perfusion-weighted imaging is a highly sensitive (95%) and specific (100%) finding of radiation necrosis. In MR spectroscopy, tumor progression shows a choline (Cho) peak which corresponds to a higher rate of metabolism in proliferative tissues, whereas RT-induced damage with cellular debris containing lactate and fatty acids contributes to lipid or lactate peak in postradiation necrosis., When compared to radiation necrosis, progressive disease shows higher Cho–creatine ratio and Cho–N-acetylaspartate ratio in MR spectroscopy. The sensitivity and specificity for identifying tumors using MR spectroscopy imaging are 89% and 83%, respectively. Recently, methionine, fluoro-l-thymidine, and fluoroethyltyrosine (FET) have been used with promising results. Of these, the FET–positron emission tomography has convincing adjunct value with a sensitivity of 100% and a specificity of 93%, comparable to some MRS results.
The management of radiation necrosis primarily depends on the presence of symptoms such as headache, nausea, cognitive impairment, seizures, or focal deficits relating to the location of the lesion. An oral corticosteroid-like dexamethasone at a dose of 4–8 mg/m2/day is the preferred first line. As many patients may need steroids for a long duration, care must be taken to address associated toxicity, such as myopathy, iatrogenic Cushing's syndrome, and gastric ulcers. Caution is advised in the dose of mannitol or other osmotic diuretics during the acute phase because there are risks of increasing intratumoral bleed and electrolyte imbalances. Nowadays, bevacizumab (anti-VEGF) is commonly used either upfront or in steroid-dependent patients with good success. A pooled analysis involving 71 patients showed that the use of bevacizumab led to a radiographic response rate of 97% and a clinical improvement rate of 79% with a mean decrease in dexamethasone of 6 mg., Other agents such as heparin, local surgery with resection of the nidus of necrosis, and hyperbaric oxygen therapy have also been tried with very little evidence of utility.
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[Figure 1], [Figure 2]