Treatment Patterns and Outcomes Among Elderly Glioblastoma Patients in Riyadh, Saudi Arabia.

BACKGROUND: Management of elderly patients with glioblastoma (GBM) is a controversial scenario and needs careful assessment and selection for aggressive radical treatment and chemotherapy protocols vs short-course radiotherapy without chemotherapy. METHODS: We evaluated treatment patterns and outcome among elderly GBM patients treated in KFMC, Riyadh. The primary endpoint is overall survival (OS) and the secondary endpoint is progression-free survival (PFS); patients were reviewed regarding radiotherapy (Rth) fractionation modalities, surgery, and chemotherapy (CTR) given in correlation to PFS, OS. RESULTS: Fifty-nine patients were recruited in our study with median age 66 (range: 60-81) years, and 47 (80%) were males. Thirty-seven patients (62.7%) had ECOG performance status (PS) ≥2, and 22 patients (37.3%) had PS <2. Gross total resection (GTR) and subtotal resection (STR) were done in 49 (82.9%) patients, and the median follow-up was 12 months. Thirty-eight (64%) patients received conventional Rth 60 Gray (Gy)/30 fractions or equal doses and 21 (36%) patients received hypofractionation Rth (40 Gy/15, 25 Gy/5 or 30 Gy/10 fractions). The median OS was 12 months (95%CI: 9.52-14.48). Receiving conventional Rth and completion of six months adjuvant CTR were significant factors for O.S (P=0.043 and 0.026), respectively. The median PFS was nine months (95%CI: 6.13-11.87). For univariate analysis, PS, time to start adjuvant treatment, and completion of six months CTR were significant factors for PFS. CONCLUSION: Conventional Rth and completion of adjuvant CTR lead to better OS, while earlier start of adjuvant treatment and the completion of adjuvant CTR were associated with a better PFS.

Multi-disciplinary approach for the management of non-metastatic non-small cell lung cancer in the Middle East and Africa: Expert panel recommendations.

The Middle East and Africa (MEA) region, a large geographical area, lies at the confluence of Asian, Caucasian and African races and comprises of a population with several distinct ethnicities. The course of management of non-small cell lung cancer (NSCLC) differs as per patients' performance status as well as stage of disease, requiring personalized therapy decisions. Although management of NSCLC has received a significant impetus in the form of molecularly targeted therapies and immune therapies in last few years, surgery remains gold standard for patients with early-stage disease. In case of unresectable disease, radiotherapy and chemotherapy are the primary management modalities. With newer therapies being approved for treatment of early stage disease, use of multi-disciplinary team (MDT) for comprehensive management of NSCLC is of prime importance. A group of experts with interest in thoracic oncology, deliberated and arrived at a consensus statement for the community oncologists treating patients with NSCLC in the MEA region. The deliberation was based on the review of the published evidence including literature and global and local guidelines, subject expertise of the participating panellists and experience in real-life management of patients with NSCLC. We present the proposed regional adaptations of international guidelines and recommends the MDT approach for management of NSCLC in MEA.

Atorvastatin in combination with radiotherapy and temozolomide for glioblastoma: a prospective phase II study.

Glioblastoma is a fast-growing primary brain tumor observed in adults with the worst prognosis. Preclinical studies have demonstrated the encouraging anticancer activity of statins. This study evaluated the efficacy of atorvastatin in combination with standard therapy in patients with glioblastoma. In this prospective, open-label, single-arm, phase II study, patients were treated with atorvastatin in combination with the standard glioblastoma therapy comprising radiotherapy and temozolomide. The primary endpoint was progression-free survival (PFS) at 6 months (PFS-6). Among 36 patients enrolled from January 2014 to January 2017, the median age was 52 (20-69) years; 22% of the patients were aged ≥60 years, and 62% were male. Patients received atorvastatin for a median duration of 6.2 (0.3-28) months. At a median follow-up of 19 months, the PFS-6 rate was 66%, with a median PFS of 7.6 (5.7-9.4) months. In terms of Grade ≥ 3 hematological adverse events, thrombocytopenia and neutropenia occurred in 7% and 12% of patients, respectively. In multivariate analyses, high baseline low-density lipoprotein levels were associated with worse survival (P = 0.046). Atorvastatin was not shown to improve PFS-6. However, this study identified that high low-density lipoprotein levels are an independent predictor of poor cancer-related outcomes. Future clinical trials testing statins should aim to enroll patients with slow-growing tumors.Clinical trial information: NCT0202957 (December 12, 2013).

The Epidemiology of Primary Central Nervous System Tumors at the National Neurologic Institute in Saudi Arabia: A Ten-Year Single-Institution Study.

OBJECTIVES: This study is aimed at describing the epidemiological trends of primary CNS tumors in children and adults at the National Neurologic Institute in Saudi Arabia. METHODS: A retrospective epidemiological approach was used where data was obtained from the department of pathology registry files and pathology reports. The records of all patients registered from January 2005 to December 2014 with a diagnosis of primary CNS tumor (brain and spinal cord) were selected. Data about sex, age, tumor location, and histologic type were collected. The classification was based on the International Classification of Diseases for Oncology, 3rd Edition (ICD-O-3). RESULTS: Nine hundred and ninety-two (992) cases of primary CNS tumors throughout the ten years (2005 to 2014) were reviewed. There were 714 (71.97%) adults and 278 (28.02%) in the pediatric age group. Nonmalignant tumors dominated the adult population (60.08%) while malignant tumors were more frequent in the pediatric population. Gliomas constituted the most common neoplastic category in children and adults. The most common single tumor entity was meningioma (26.99%, ICD-O-3 histology codes 9530/0, 9539/1, and 9530/3). Medulloblastomas (ICD-O-3 histology codes 9470, 9471, and 9474) were the most common single tumor entity in the pediatric age group (26.62%). CONCLUSIONS: This is an institution-based, detailed, and descriptive epidemiological study of patients with primary CNS tumors in Saudi Arabia. In contrast to other regional and international studies, the medulloblastomas in our institution are more frequent than pilocytic astrocytomas. Limitations to our study included the referral bias and histology-based methodology.

Management and treatment recommendations for World Health Organization Grade III and IV gliomas.

The treatment recommendations provided in this manuscript are intended to serve as a knowledge base for clinicians and health personals involved in treating patients with high-grade malignant glioma. In newly diagnosed patients, complete resection or biopsy is required for histological characterization of the tumor, which in turn is essential to decide the treatment strategy. In patients with good or borderline performance score, radiotherapy (RT), and chemotherapy are the preferred management. In patients with poor performance score, RT with best possible supportive care is the mainstay of the management. All patients have to undergo brain magnetic resonance imaging procedure quarterly or half-yearly for 5 years and then on an annual basis. In patients with recurrent malignant glioma, wherever possible re-resection or re-irradiation or chemotherapy can be considered along with supportive and palliative care. High-grade malignant glioma should be managed in a multidisciplinary center with the best of the possible care that is available based on the evidence as discussed in this manuscript.

Atypical Teratoid/Rhabdoid Tumor of the Sellar Region in an Adult With Long Survival: Case Report and Review of the Literature.

Atypical teratoid/rhabdoid tumor (AT/RT) is a highly malignant central nervous system neoplasm usually diagnosed in young children, although it can occur in adults. Prognosis for AT/RT is poor, with a median survival of 10 - 11 months. We report a rare case of adult sellar and suprasellar AT/RT in a 36-year-old female patient. She was treated with multi-modalities including surgery, chemotherapy and radiation. She markedly improved following treatment with no recurrence in 3 years follow-up. To our knowledge, this is the 11th case of an adult-onset AT/RT in the sellar or suprasellar region with favorable long-term outcome.

Outcome of patients with glioblastoma in Saudi Arabia: Single center experience.

Glioblastoma multiforme (GBM), the most common primary brain tumor in adults, is associated with one of the worst 5 year survival rates among all human cancer types. To date, no published data are available for the outcome of this disease in Saudi Arabia. The present study performed a single-center, retrospective cohort study to evaluate the outcome of patients with GBM in Saudi Arabia. The Comprehensive Cancer Center at King Fahad Medical city (Riyadh, Saudi Arabia) was used in the present study. All adult patients (≥18 years) diagnosed with histologically proven GBM between January 2008 and December 2013 were included in the present study. A total of 90 patients were treated during the specified period. Of this, 73 (81%) patients underwent resection and 17 (19%) had biopsy only. The majority of patients (n=88; 98%) received radiotherapy (XRT): 67 (76%) with standard and 21 (24%) with hypo-fractionated dosage. Of the total patients, 65 (72%) received combined modality therapy [standard XRT concurrently with Temozolmide (TMZ)]. The 6 month progression-free survival rate was 43% for all patients and 55% for the combined modality subgroup. The median overall survival (OS) for all patients was 13.7 months. However, the median OS for patients treated with combined modality was 19.7 months. In this single-center retrospective study, the outcomes of patients with GBM were similar to those in previously reported studies. An improved outcome was associated with an improved performance status, absence of residual disease and use of adjuvant TMZ.

Quality of reporting of chemotherapy compliance in randomized controlled trials of breast cancer treatment.

OBJECTIVE: The Consolidated Standards of Reporting Trials statement requires detailed reporting of interventions for randomized controlled trials. We hypothesized that there was variable reporting of chemotherapy compliance in published randomized controlled trials in breast cancer, and therefore surveyed the literature to assess this parameter and determine the study characteristics associated with reporting quality. METHODS: Published Phase III randomized controlled trials (January 2005-December 2011; English language) evaluating chemotherapy in breast cancer were identified through a systematic literature search. Articles scored 1 point each for reporting of the four measures: number of chemotherapy cycles, dose modification, early treatment discontinuation and relative dose intensity. Logistic regression identified study characteristics associated with reporting quality score of ≥ 2. RESULTS: Of the 115 eligible randomized controlled trials, 79 (69%) were published in high-impact journals, 66 (57%) were published since 2008, 43 (37%) reported advanced-stage disease and 37 (32%) were industry sponsored. Relative dose intensity, number of cycles, dose modification and early treatment discontinuation were reported in 70 (61%), 53 (46%), 65 (57%) and 81 (70%) articles, respectively. Eighty-two (71%) articles showed a quality score of ≥ 2; 25 (22%) articles reported all four compliance measures. Articles published since 2008 (P = 0.035) and those reporting advanced-stage disease (P < 0.001) showed significantly higher quality of compliance. CONCLUSIONS: Our results demonstrate variable reporting of chemotherapy compliance in published randomized controlled trials with a modest improvement noted in recent years. Incorporating standards for reporting chemotherapy compliance in scientific guidelines or the journal peer review process may decrease the variability and improve the quality of reporting.

Statins are potential anticancerous agents (review).

Statins are inhibitors of 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), which is a rate-limiting enzyme in the mevalonate pathway. The pleiotropic effects of statins may be mediated by the inhibition of downstream products such as small GTP-binding proteins, Rho, Ras and Rac whose localization and function are dependent on isoprenylation. Preclinical studies of statins in different cancer cell lines and animal models showed antiproliferative, pro­apoptotic and anti-invasive effects. Notably, statins showed targeted action in cancerous cell lines compared to normal cells. Previous studies have also shown the synergistic effects of statins with chemotherapeutic agents and radiotherapy. This effect of statins was also observed in chemotherapeutic-resistant tumors. Statins were reported to sensitize the cells to radiation by arresting them in the late G1 phase of the cell cycle. Similarly, population-based studies also demonstrated a chemopreventive and survival benefit of statins in various types of cancers. However, this benefit has yet to be proven in clinical trials. The inter-individual variation in response to statins may be contributed to many genetic and non-genetic factors, including single-nucleotide polymorphisms in HMGCR gene and the overexpression of heterogeneous nuclear ribonucleoprotein A1, which was reported to reduce HMGCR enzyme activity. However, more studies with large phase III randomized controlled trials in cancer patients should be conducted to establish the effect of stains in cancer prevention and treatment.

Discordance between conclusions stated in the abstract and conclusions in the article: analysis of published randomized controlled trials of systemic therapy in lung cancer.

PURPOSE: Clinicians may read only the abstract of an article to keep abreast of newly published randomized controlled trials (RCTs). However, discordances have been noticed in summary conclusions in the abstracts and the main body of some articles. This article evaluated such discordances in detail. METHODS: RCTs of systemic therapy for lung cancer published between 2004 and 2009 were considered. Conclusions in the body of the articles and those in the abstracts were graded by using a 7-point Likert scale; 1 for strong endorsement of the control arm, 4 for a neutral statement, and 7 for strong endorsement of the experimental arm. Conclusions were classified as discordant if the difference in scores was ≥ 2. χ(2) tests and logistic regression were used to identify factors associated with discordance. RESULTS: From among 114 eligible RCTs identified (90 for non-small-cell and 24 for small-cell lung cancer), 11 (10%) articles presented discordant conclusions in the abstract and in the body of the articles. Discordance was most common when the experimental arm was strongly supported in the abstract but not in the body of the article (nine of 11; 82%); however, the converse was much less common (two of 11; 18%; P < .001). Intraclass correlations for the two reviewers were ≥ 0.9. The discordances were found to be independent of trial-related factors. CONCLUSION: Conclusive statements in the abstract can differ from those in the full text. Clinicians should use caution when they consider making changes in their practice on the basis of reading only the abstract of a published RCT.