The Mystery of Multiple Masses: A Case of Anaplastic Astrocytoma.
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ABSTRACT:
SUBMITTER: Sethi P
PROVIDER: S-EPMC5522018 | biostudies-other | 2017 Jun
REPOSITORIES: biostudies-other
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Project description:Anaplastic astrocytomas are aggressive glial cancers that present poor prognosis and high recurrence. Heterozygous IDH1 R132H mutations are common in adolescent and young adult anaplastic astrocytomas. In a majority of cases, the IDH1 R132H mutation is unique to the tumor, although rare cases of anaplastic astrocytoma have been described in patients with mosaic IDH1 mutations (Ollier disease or Maffucci syndrome). Here, we present two siblings with IDH1 R132H mutant high grade astrocytomas diagnosed at 14 and 26 years of age. Analysis of IDHR132H mutations in the siblings' tumors and non-neoplastic tissues, including healthy regions of the brain, cheek cells, and primary teeth indicate mosaicism of IDHR132H. Whole exome sequencing of the tumor tissue did not reveal any other common mutations between the two siblings. This study demonstrates the first example of IDH1 R132H mosaicism, acquired during early development, that provides an alternative mechanism of cancer predisposition.
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Project description:Gliomas are one of the most common tumors of the central nervous system, which cause significant morbidity and mortality. Glioblastoma (GBM) is an aggressive and debilitating disease, which is the most common primary brain tumor in adults. Despite optimal surgical resection followed by radiotherapy and adjuvant chemotherapy, prognosis of patients with GBM remain poor. Tumor-treating fields (TTFields), as a novel treatment approach, is being explored through increased clinical application. Herein, we report the case of a 46-year-old man who was diagnosed as anaplastic astrocytoma [World Health Organization (WHO) III grade], IDH1 R132 mutation, IDH2 R172 mutation, and a methylated MGMT promoter, without 1p36 and 19q13 heterozygosity loss. About 2.5 months after surgery, the patient presented with seizures, aphasia, and memory loss. Following the first-line treatment, TTFields was shown to be a valuable treatment option to control clinical symptom burden. The use of TTFields was shown to prolong progression-free survival and delay the pathological upgradation to glioblastoma. Notably, combined TTFields and chemotherapy might be beneficial in terms of risk reduction for pathological upgradation. To the our current knowledge, this is the first case report that attempts to offer possible strategies based on TTFields toward delaying pathological upgradation from anaplastic astrocytoma (WHO III grade) to glioblastoma.
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Project description:BackgroundIt has become increasingly common to incorporate adjuvant chemotherapy with radiotherapy in the treatment of resected anaplastic astrocytoma based on results from recent phase II/III randomized trials. However, whether or not combined chemoradiotherapy is associated with improved survival outcome in patients who undergo "biopsy only" is less clear.MethodsThe US National Cancer Database was used to identify patients with histologically confirmed, biopsy-only anaplastic astrocytoma who received either radiotherapy alone or combined chemoradiotherapy from 2006 through 2014.ResultsIn total, 1896 patients with biopsy-only anaplastic astrocytoma were included, among whom 363 (19.1%) received radiotherapy alone and 1533 (80.9%) received combined chemoradiotherapy. The median age at diagnosis was 60 years. Combined chemoradiotherapy was associated with a significant survival benefit when compared with radiotherapy alone on univariable analysis (median, 13.2 versus 5.6 months; hazard ratio [HR], 0.57; 95% confidence interval [CI], 0.50-0.65; p < 0.001) and on multivariable analysis (HR, 0.62; 95% CI, 0.55-0.71; p < 0.001). A significant survival benefit for combined chemoradiotherapy persisted in a propensity score-matched analysis (HR, 0.67; 95% CI, 0.56-0.78; p<0.001).ConclusionsOur results suggest that combined chemoradiotherapy may be associated with significantly improved survival over radiotherapy alone in patients with anaplastic astrocytoma who undergo biopsy only.
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