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FullText PDF Abstract Brain metastases are the most common neurological complications of adult cancers, accounting for more than half of brain tumors. The incidence of brain metastases may be increasing due to improved detection of small lesions by advanced imaging technologies.
Given the fast evolution of targeted and immunotherapy regimens, it is essential to serially assess brain malignancies during the disease course for disease monitoring and tailoring of the therapeutic management. For such serial and repetitive assessment, cerebrospinal fluid CSF could be the biological fluid of choice to supplement cytology examination for the presence or absence of CNS malignancy, as well as provide extensive information on tumor mutational profile for personalization of treatment.
Among of all the cancer types, lung cancer, breast cancer, and melanoma are the most frequent to metastasize to brain [ 1 ]. Brain metastases are most frequently found within the brain parenchyma, cranium, dura, and leptomeninges.
For an established diagnosis of primary malignancy, the brain metastatic lesions are not always biopsied due to the invasiveness of the procedures. Yet, for the cancer of unknown primary CUP cases, the brain lesion biopsies are warranted to establish the diagnosis.
Nevertheless, in both scenarios, given the spatial and temporal intratumoral heterogeneity, repeated or serial biopsies are required for an adequate buffalo business report of the somatic genetic alterations for better management during the disease course [ 6 - 8 ].
The tissue biopsy approach for brain lesion sampling has major pitfalls given the limited access to the tumor and the invasiveness of the necessary procedures, along with sampling bias due to tumor heterogeneity.
Recently, cell-free circulating tumor DNA ctDNA in the peripheral blood has been used to characterize and monitor various types of cancer [ 8 - 11 ].
However, plasma-derived ctDNA analysis of patients with only central nervous system CNS lesions revealed either absence or very low levels of tumor DNA in the peripheral circulation [ 12 ]. Given the routine, frequent CSF cytology examinations for patients with brain lesions, it could be clinically beneficial to analyze CSF-ctDNA for presence or absence of CNS malignancy and further personalization of the treatment plans.
Case Report A year-old woman with no past history of cancer presented to an outside hospital with severe headache and lower back pain in June Brain MRI showed hydrocephalus due to leptomeningeal metastases and a focal mass in the spinal cord adjacent to cerebellum.
The large spinal tumor causing the cord compression was excised, histopathological examination of which confirmed adenocarcinoma. To alleviate the symptoms, a ventriculo-peritoneal shunt was placed, and an Ommaya reservoir was implanted to deliver intrathecal chemotherapy with methotrexate, which ultimately yielded poor response after six cycles.
In Augustthe patient was referred to our hospital, where she was extensively evaluated and given several targeted and immunotherapeutic regimens including gefitinib, trastuzumab, lapatinib, ipilimumab, pembrolizumab, and chemotherapy drugs such as 5-fluorouracil, epirubicin, cyclophosphamide, docetaxel, carboplatin, and capecitabine.
Despite myriads of regimens tried, only anti-HER2 therapy resulted in clinical benefit and alleviated lower extremity muscle spasticity and maintained adequate consciousness level. In Septemberthe spasticity in all four extremities worsened, and the patient started to manifest dysarthria and dysphagia.
MRI demonstrated multiple enhanced lesions Fig. Considering the CSF-ctDNA NGS results and recommendations, ado-trastuzumab emtansine was added to the combination regimen of intrathecal trastuzumab and oral lapatinib. Given the CDKN2A mutation, palbociclib was also tried for three weeks, but discontinued due to myelosuppressive side effects.
Within two weeks from implementation of a new anti-HER2 regimen combination, the neurological signs of the patient dramatically improved and tumor markers such as CEA and CA decreased significantly. The following CSF cytology examinations confirmed an absence of malignant cells in three subsequent spinal taps.
Currently the patient appears well. Magnetic resonance imaging of the brain after gadolinium injection. Cytology examination of CSF. Discussion There is an obvious need for sensitive and specific markers to monitor tumor dynamics of both primary as well as metastatic CNS lesions.
The decision to analyze CSF beyond cytology examination was due to a limited accessibility to the brain lesions and invasiveness of the biopsy procedure. At the same time, the CSF was available as part of standard of care for cytology examination.
In this patient with CUP, CSF-ctDNA analysis helped to characterize the most current tumor mutational profile, corroborate cytology results, and refine the treatment protocol resulting in a clinical remission.
CSF is the biological fluid of choice that is amenable for serial monitoring of CNS tumors, and could be obtained via lumbar puncture. Although the latter is not a noninvasive procedure, it still qualifies as minimally invasive procedure and is currently routinely performed to follow up brain tumor patients with primary or metastatic lesions [ 14 - 16 ].
Cytology examination of CSF provides limited information and is characterized by low sensitivity and specificity [ 17 ]. For now, we envision CSF-ctDNA to be used in combination with cytology examination and imaging along with clinical parameters.
In addition to presence or absence of CNS malignancy, CSF-ctDNA analysis may help provide clinically actionable information that may further personalize the treatment protocols for each individual patient and tailor their disease management plan.Buffalo State, a SUNY campus located in Buffalo, NY, offers degrees in teacher education, visual and performing arts, sciences, and professional studies.
Buffalo State, a SUNY campus located in Buffalo, New York's Elmwood Village, offers degrees in education, the arts, science, and professional studies.
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