Gliomas are the most common subgroup of primary malignant brain tumors in adults, constituting >40% of all primary CNS neoplasms. Although all gliomas originate from neuroepithelial tissues, they vary considerably in morphology, location, genetic alterations and in their response to therapy. The most malignant of gliomas (Grade IV) is Glioblastoma Multiforme (GBM), causing over 10,000 deaths each year in the US alone. Despite robust therapeutic advances, median survival for GBM still remains 14-20 months with very high tumor recurrence rate. Various investigation modalities are available for establishing diagnosis of glioma, like: CT scan, MRI, X-ray, spinal tap, angiogram, myelogram & biopsy, though, histopathology represents the gold standard for their typing & grading. However, even this remains unsatisfactory because of the lack of reproducibility and absence of precision. Development of objective, diagnostic, prognostic & predictive markers for these lethal neoplasms is therefore a priority. Biomarkers for glioma can be identified in various biological samples like: DNA, mRNA, cell surface receptors, transcription factors, secretory proteins, metabolites or processes such as proliferation, angiogenesis or apoptosis. Tumor biomarkers help oncologists in managing gliomas at various levels, from screening till assessment of longitudinal response to therapy. Identifying the molecular & pathogenetic characteristics of glioma regulation network may increase the precision of customized medication. Further, the proteomic approach has the potential to identify novel diagnostic, prognostic and therapeutic biomarkers. In the near future, improved proteomic profiling is anticipated to bring about a merger of biology, engineering and informatics, with a profound impact on glioma research and treatment. Optimization of experimental design and validation in independent cohorts, improved multiplex proteomic methodologies and bioinformatics tools, and their integration with genetic and metabolomic profiling technologies promise to play critical roles in the post proteomics era of cancer diagnosis and treatment.
Background: Gliomas are the most common primary brain tumors. The combination of surgery, post-operative radiotherapy with concurrent and adjuvant chemotherapy represents the standard approach to the treatment of high grade gliomas. Threedimensional conformal therapy (3DCRT) is increasingly used in the treatment of primary brain tumours. The use of intensitymodulated radiotherapy (IMRT) yields conformal dose distributions and better avoidance of organs at risk. Memory impairment is a well-documented side effect of cranial irradiation. One possible hypothesis focuses on a neurogenic stem cell compartment in the hippocampus that is highly sensitive to radiation and potentially central to radiation-induced memory impairment. Objectives: In this study we evaluated the possibility of sparing the hippocampi in post-operative radiation therapy for high grade glioma (3DCRT/IMRT technique) and its impact on preservation of memory function. Methods: A total of 20 newly diagnosed, histologically confirmed cases of high grade glioma fulfilling the eligibility criteria were enrolled into the study. Patients received post-operative radiation therapy with concurrent and adjuvant temozolomide via the 3DCRT (3DCRT arm) / IMRT (IMRT arm) technique. Evaluation of dose to hippocampi (ipsilateral and contralateral) was done along with serial evaluation of memory function. Two groups were compared for the dose received by hippocampi and its impact on memory function. Results: Bilateral hippocampal sparing was achieved in all patients in IMRT arm. Whereas, in 3DCRT arm ipsilateral, hippocampus could be spared in 60% of patients. Memory function analysis showed that patients in IMRT arm had maintenance of the score for a period of 3 months post radiotherapy, while patients in 3DCRT arm showed a decline immediately after radiotherapy. Conclusions: Bilateral hippocampal sparing with preservation of memory function is achievable with IMRT technique for delivery of post-operative radiotherapy in patients with high grade glioma without compromise in prescribed dose delivery.
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