Temozolomide-induced myelotoxicity and single nucleotide polymorphisms in the MGMT gene in patients with adult diffuse glioma: a single-institutional pharmacogenetic study

Journal of Neuro-Oncology - Nearly 10% of patients with adult diffuse glioma develop clinically significant myelotoxicity while on temozolomide (TMZ) leading to treatment interruptions. This study...     

Cost-effectiveness of the bird''s nest filter for preventing pulmonary embolism among patients with malignant brain tumors and deep venous thrombosis of the lower extremities

Patients with malignant brain tumors and deep venous thrombosis (DVT) of the lower extremities are at high risk of developing pulmonary embolism (PE). We developed a Markov model to compare the cost-effectiveness of two strategies to prevent PE in such patients: intra-vena-caval bird's nest filter (BNF) with anticoagulation versus anticoagulation alone. Using the benchmark of US $50,000 per quality-adjusted life year (QALY), BNF was not cost-effective in this population as it reduced the rate of PE at an incremental cost-effectiveness ratio of $198,852 per QALY gained. However, after adjusting the model to reflect the 5-year mortality rate of hypothetical breast cancer patients, BNF was more effective and less expensive than anticoagulation alone. BNF was effective in reducing the rate of PE but was not cost-effective for patients with brain tumors. BNF could be cost-effective for patients with longer life expectancies.Presented in part at the 36th American Society of Clinical Oncology Meeting, May 2000.     

Real-time PCR assay based on the differential expression of microRNAs and protein-coding genes for molecular classification of formalin-fixed paraffin embedded medulloblastomas

Background

Medulloblastoma has recently been found to consist of 4 molecularly and clinically distinct subgroups: WNT, Sonce hedgehog (SHH), Group 3, and Group 4. Deregulated microRNA expression is known to contribute to pathogenesis and has been shown to have diagnostic and prognostic potential in the classification of various cancers.

Methods

Molecular subgrouping and microRNA expression analysis of 44 frozen and 59 formalin-fixed paraffin embedded medulloblastomas from an Indian cohort were carried out by real-time RT-PCR assay.

Results

The differential expression of 9 microRNAs in the 4 molecular subgroups was validated in a set of 101 medulloblastomas. The tumors in the WNT subgroup showed significant (P < .0001) overexpression of miR-193a-3p, miR-224, miR-148a, miR-23b, and miR-365. Reliable classification of medulloblastomas into the 4 molecular subgroups was obtained using a set of 12 protein-coding genes and 9 microRNAs as markers in a real-time RT-PCR assay with an accuracy of 97% as judged by the Prediction Analysis of Microarrays. Age at diagnosis, histology, gender-related incidence, and the relative survival rates of the 4 molecular subgroups in the present Indian cohort were found to be similar to those reported for medulloblastomas from the American and European subcontinent. Non-WNT, non–SHH medulloblastomas underexpressing miR-592 or overexpressing miR-182 were found to have significantly inferior survival rates, indicating utility of these miRNAs as markers for risk stratification.

Conclusions

The microRNA based real-time PCR assay is rapid, simple, inexpensive, and useful for molecular classification and risk stratification of medulloblastomas, in particular formalin-fixed paraffin embedded tissues, wherein the expression profile of protein-coding genes is often less reliable due to RNA fragmentation.     

Toxicity with radiotherapy for oral cancers and its management: a practical approach

Radiotherapy-induced damage in the oral mucosa is the result of the deleterious effects of radiation, not only on the oral mucosa itself but also on the skin, adjacent salivary glands, bone, dentition, and masticatory apparatus. From basic skin care to dental and oral health maintenance, several ointments and lotions, oral and parenteral medications, biological response modifiers, cytoprotective drugs, newer radiation techniques and surgery have been introduced to combat and more importantly to prevent the development of these complications. Radiotherapy-induced oral complications involve complex and dynamic pathobiological processes. This in the immediate- and long-term course lowers the quality of life and predisposes patients to serious clinical disorders. Here, we focus on these oral complications of radiotherapy, highlight preventive and therapeutic developments, and review the current treatment options available for these disorders.     

Factors influencing activities of daily living using FIM–FAM scoring system before starting adjuvant treatment in patients with brain tumors: results from a prospective study

Background Patients with brain tumors have varied degree of functional and psychological impairments because of factors relating to the tumor or to the treatment they receive. The functional independence measurement and functional activity measurement system (FIM–FAM) is an activity of daily living (ADL) scoring system that may be able to determine impairments in different domains objectively. Material and method From August 2007 to April 2008, 150 consecutive adult (>18 years) primary brain tumor patients (median age 40 years; male 88, female 62) registered in a general out-patient neuro-oncology clinic were accrued and detailed data were recorded. Seventy percent had malignant tumor (66% high-grade and 34% low-grade; 70% intra-axial). Glioblastoma (GBM) (23.3%), anaplastic astrocytoma (AA) (18.7%), and diffuse fibrillary astrocytoma (18.7%) were the commonest histologic subtypes. The common sites for tumors included frontal region (30.7%), posterior fossa (12%), and left parietal region (11.3%). A detailed baseline pre-radiotherapy (pre-RT) ADL assessment was done with the FIM–FAM scoring system, which has seven domains with 30 sub-domains (maximum and minimum total scores are 210 and 30). Results The mean total FIM–FAM score of the entire patient population was 167.5 (range 30–208). Scores in self care, sphincter control, mobility items, locomotion, communication items, psychological, and cognitive item domains were 39.49, 10.95, 22.70, 16.44, 28.93, 18.96, and 30.1, respectively. Univariate analysis showed total FIM–FAM scores not significantly different with age (≤35 years vs. >35 years; P = 0.994), sex (male versus female; P = 0.133), and grade of the tumor (high-grade versus low-grade; P = 0.142) but were significantly higher in patients with a Karnofsky performance score (KPS) of ≥70 as compared with <70 (P = 0.001), neurological performance scale (NPS) of 0 or 1 vs. 2 or 3; P = 0.001), disease type (benign versus malignant; P = 0.001), and site of disease (cerebral versus cerebellar; P = 0.024). Multivariate analysis confirmed these findings for KPS (P = 0.001) and NPS (P = 0.012) only. Age was a significant factor for poorer cognitive function (P = 0.005), psychological (P = 0.045), and self care function (P = 0.001). A trend for correlation between tumor sites with the corresponding function as assesses on the FIM–FAM score was observed. Mobility domain scores were poor for left parietal domain and psychosocial for frontal lobe lesion. Pearson correlation test demonstrated a significant correlation between KPS and NPS with FIM–FAM scores (P = <0.001). Average time to perform the FIM–FAM was 15–20 min. Conclusion FIM–FAM system is relatively simple, easy to perform in routine clinical practice and may be used as a tool for assessment of rehabilitation program. There is strong correlation with age, type of tumor, and site of disease with different functional and cognitive domain impairment.     

Intraoperative blood loss in orthotopic liver transplantation: The predictive factors

Liver transplantation has been associated with massive blood loss and considerable transfusion requirements. Bleeding in orthotopic liver transplantation is multifactorial. Technical difficulties inherent to this complex surgical procedure and pre operative derangements of the primary and secondary coagulation system are thought to be the principal causes of perioperative hemorrhage. Intraoperative practices such as massive fluid resuscitation and resulting hypothermia and hypocalcemia secondary to citrate toxicity further aggravate the preexisting coagulopathy and worsen the perioperative bleeding. Excessive blood loss and transfusion during orthotopic liver transplant are correlated with diminished graft survival and increased septic episodes and prolonged ICU stay. With improvements in surgical skills, anesthetic technique, graft preservation, use of intraoperative cell savers and overall perioperative management, orthotopic liver transplant is now associated with decreased intra operative blood losses. The purpose of this review is to discuss the risk factors predictive of increased intra operative bleeding in patients undergoing orthotopic liver transplant.