Patterns of care and outcomes of multi-agent versus single-agent chemotherapy as part of multimodal management of low grade glioma

Abstract

For high-risk low-grade gliomas (LGGs), adjuvant radiotherapy (RT) with procarbazine/lomustine/vincristine (PCV) chemotherapy increases overall survival (OS) over RT alone. However, in practice, temozolomide (TMZ) is often used instead of PCV. Using the National Cancer Data Base (NCDB), we provide the first investigation of practice patterns and outcomes of chemoradiotherapy with single-agent chemotherapy (SAC, analogous to TMZ) or multi-agent chemotherapy (MAC, analogous to PCV) for LGG. Patients with high-risk Grade II LGGs were queried in the NCDB. Inclusion was limited to patients treated with definitive RT and chemotherapy. Patients were divided into cohorts receiving SAC or MAC. Kaplan–Meier analysis compared overall survival (OS), and Cox proportional hazards models determined variables independently associated with OS. Of 1029 patients, 989 (96.1%) received SAC, while 40 (3.9%) received MAC. Patients treated more recently (2010–2012) were less likely to receive MAC (p = 0.029). No differences in median OS were observed between patients treated with MAC and SAC (45.3 vs. 59.2 months, p = 0.861). Independent predictors of worse OS included age >40, high Charlson–Deyo index, other governmental/unrecorded insurance status, biopsy only, astrocytoma histology, Western geographical region, and higher income. Substuting MAC with SAC had no impact on OS (p = 0.804). There is a significantly greater utilization of SAC compared to MAC in the US. There were no differences in OS between patients receiving SAC and MAC, nor did this factor impact OS on multivariate analysis, suggesting that the practice of substituting MAC with SAC for management of LGG may not adversely affect outcome.

from Cancer via ola Kala on Inoreader http://ift.tt/2p4P4oT
via IFTTT

CDC20 with malignant progression and poor prognosis of astrocytoma revealed by analysis on gene expression

Abstract

The malignant transformation of astrocytoma may result from the accumulation of multiple genetic alterations. Current research shows that diffuse astrocytoma (AIIs, WHO grade II) is inherently predisposed to recur locally, and to spontaneously progress to anaplastic astrocytoma (AAIIIs, WHO grade III) and eventually secondary glioblastoma (sGBMIVs, WHO grade IV). The aim of the study was to identify and validate the important gene(s) associated with malignant progression and poor prognosis of astrocytoma. Average expression levels of 82 samples (35 AIIs, 13 AAIIIs and 34 sGBMIVs) were compared to each other through no-paired student test. Candidate genes were screened by DAVID and Kaplan–Meier survival analysis. Further, the significant candidate genes were validated through real-time PCR(qPCR), western blot and immunohistochemistry (IHC) in different grades of glioma. Finally, the association of target gene and clinical molecular characterization was analyzed by Chi-squared analysis. The cell-division cycle protein 20(CDC20, p = 0.0129) and the polo-like kinase 1(PLK1, p = 0.0046) were screened by statistical and Kaplan–Meier survival analysis. The expression levels of CDC20 and PLK1 rose significantly through real-time PCR(qPCR), western blot and IHC. A chi-squared analysis showed that patients with CDC20 high-expression differ from patients with CDC20 low-expression in terms of WHO classification (p < 0.0001), karnofsky performance score (KPS, p < 0.0001), isocitrate dehydrogenase mutation (IDH1, p < 0.0001), phosphatase and tensin homolog mutation (PTEN, p = 0.027) and epidermal growth factor receptor protein amplification (EGFR, p = 0.048). Moreover, the biological processes analyses indicate CDC20 might have an essential role in astrocyte cell proliferation. We demonstrated that the expression level of CDC20 increases significantly along with malignant progression and poor prognosis of astrocytoma.

from Cancer via ola Kala on Inoreader http://ift.tt/2oxtIwD
via IFTTT

Pathological analysis of the surgical margins of resected glioblastomas excised using photodynamic visualization with both 5-aminolevulinic acid and fluorescein sodium

Abstract

During glioma resection, 5-aminolevulinic acid (5-ALA) and fluorescein sodium (Fl-Na) are used for photodynamic tumor visualization. The objective of this study was to evaluate the pathological findings of the boundary zone between the tumor and adjacent normal brain in glioblastoma patients undergoing simultaneous double staining with 5-ALA and Fl-Na during surgery. Eight patients received 5-ALA (20 mg/kg orally) before the induction of general anesthesia, and Fl-Na (20 mg/kg) was administered intravenously before the dural incision was performed. The tumor bulk was removed under the guidance of Fl-Na staining alone using conventional white light. Subsequently, residual tumor was removed under the guidance of both fluorescent agents within functionally safe limits until both were visibly undetectable. Twenty specimens exhibiting different staining intensities of both agents were obtained. The vessel index (VI) was calculated from CD31 immunohistochemistry (IHC) samples. Boundary zone tumor cells were detected by IHC for olig2, and were expressed as the olig2 index (OLI). The VI was significantly higher in Fl-Na-positive areas than in Fl-Na-negative areas (p = 0.0005). In contrast, the OLI was significantly higher in 5-ALA-positive areas than in 5-ALA-negative areas (p = 0.0149). 5-ALA-positive/Fl-Na negative areas were observed in 7 patients. These findings indicate that Fl-Na accumulates in areas with a disrupted blood–brain barrier, and that 5-ALA fluorescence is dependent on tumor cell protoporphyrin IX metabolism. In conclusion, 5-ALA was better for detecting tumor cells in the boundary zone than was Fl-Na. Of note, tumor cells existed outside the fluorescence-stained boundaries of both agents.

from Cancer via ola Kala on Inoreader http://ift.tt/2pnI2wp
via IFTTT

Rituximab, methotrexate, procarbazine, vincristine and intensified cytarabine consolidation for primary central nervous system lymphoma (PCNSL) in the elderly: a LOC network study

Abstract

Primary CNS lymphoma (PCNSL) is chemosensitive to high-dose methotrexate-based chemotherapy. However, responses in the elderly are short-lasting and outcome is poor. Given that radiotherapy and intensive chemotherapy expose elderly to severe toxicities, alternative consolidation approaches need to be evaluated. In this multicenter study, we retrospectively analyzed consecutive patients with newly-diagnosed PCNSL, aged >60, treated with a (R)-MPV-AAA regimen. The regimen consisted of three 28-day cycles of methotrexate (3.5 g/m² D1, D15), procarbazine, vincristine, followed by three 28-day cycles of cytarabine consolidation (3 g/m² D1-2). Addition of rituximab (375 mg/m² D1) was optional. The results were compared with the historical MPV-A regimen. Ninety patients received the (R)-MPV-AAA regimen with (n = 39) or without (n = 51) rituximab. Median age was 68 and median KPS 60. 55% of patients achieved a complete response, 8% a partial response and 37% progressed. The median PFS was 10 months, the median OS 28.1 months. Toxicity was mainly hematological, with 54 and 51% of grade III-IV neutropenia and thrombopenia. The response rate was higher in patients receiving rituximab (77 vs. 53%; p = 0.03), whereas no difference was observed in terms of PFS or OS. When comparing the results to the historical MPV-A, there was no difference in terms of response rate, PFS or OS, but a higher rate of hematotoxicity. This study suggests that extending cytarabine consolidation after methotrexate-based chemotherapy does not improve the MPV-A efficacy but increases toxicity in the elderly. The addition of rituximab may improve the response rate, but its impact on final outcome remains unclear.

from Cancer via ola Kala on Inoreader http://ift.tt/2oRBWmA
via IFTTT

Expression and function of ABCG2 and XIAP in glioblastomas

Abstract

Despite multimodal treatment that includes surgery, radiation and chemotherapy, virtually all glioblastomas (GBM) recur, indicating that these interventions are insufficient to eradicate all malignant cells. To identify potential new therapeutic targets in GBMs, we examined the expression and function of proteins that are associated with therapy resistance and cancer cell survival. We measured the expression of eight such proteins in 50 GBM samples by immunohistochemistry and analyzed patient survival. We report that GBM patients with high expression of ABCG2 (also called BCRP) or XIAP at the protein level had worse survival than those with low expression. The adjusted hazard ratio for ABCG2 was 2.35 and for XIAP was 2.65. Since glioma stem cells (GSCs) have been shown to be more resistant than bulk tumor cells to anti-cancer therapies and to express high levels of these proteins, we also sought to determine if ABCG2 and XIAP have functional roles in GSCs. We used small molecule inhibitors to treat patient-derived GBM tumorspheres in vitro and observed that inhibitors of ABCG2, Ko143 and fumitremorgin, significantly reduced self-renewal. These results suggest that ABCG2 and XIAP proteins may be useful indicators of patient survival and that inhibition of ABCG2 may be a promising therapeutic strategy in GBMs.

from Cancer via ola Kala on Inoreader http://ift.tt/2pMFF3a
via IFTTT

Does pregnancy influence melanoma prognosis? A meta-analysis.

The literature has not been able to conclude whether pregnancy influences the prognosis of melanoma. The aim of this study was to explore the prognosis of melanoma diagnosed during pregnancy or post partum [pregnancy-associated melanoma (PAM)] compared with melanoma in female patients who were not pregnant. We systematically searched for studies of female patients with melanoma that reported outcomes related to survival. Fifteen eligible studies were found. Overall, PAM was associated with a 17% higher mortality compared with melanoma diagnosed in female patients who were not pregnant (hazard ratio=1.17, 95% confidence interval: 1.03-1.33, P=0.02). The heterogeneity associated with this test was moderate (P=0.07; I2=38%). PAM was also associated with a 50% higher recurrence rate compared with melanoma not associated with pregnancy (hazard ratio=1.50, 95% confidence interval: 1.19-1.90, P

http://ift.tt/2pPe705

Prognostic significance of histologic subtype in pStage I lung adenocarcinoma

Abstract

The International Association for the Study of Lung Cancer, the American Thoracic Society, and the European Respiratory Society (IASLC/ATS/ERS) proposed a new histologic classification of lung adenocarcinoma in 2011. While several studies have already validated the prognostic value of this new classification of lung adenocarcinoma, we conducted own investigation in the present study. This study included 197 patients with invasive lung adenocarcinoma who underwent complete resection. Pathologic diagnoses were made in accordance with the new IASLC/ATS/ERS classification for lung adenocarcinoma. The lepidic/acinar/papillary group had a significantly better prognosis than the micropapillary/solid/invasive mucinous adenocarcinoma group (5-year recurrence-free survival [RFS] 73 vs. 21%: p < 0.01, 5-year overall survival 85 vs. 52%: p < 0.01). Age (hazard ratio [HR], 1.898; p = 0.03), CEA (HR, 1.873; p = 0.03), pStage (HR, 6.149; p < 0.01), and histologic subtype (HR, 2.342; p = 0.01) were independent prognostic factors for the RFS. Furthermore, age (HR, 3.242; p = 0.04), CEA (HR, 3.405; p = 0.03) and histologic subtype (HR, 11.108; p < 0.01) were independent prognostic factors for the progression-free survival in pStage I. The histologic subtype correlated with the prognosis of pStage I of lung adenocarcinoma. Patients in the high-grade group of lung adenocarcinoma, which included solid, micropapillary and invasive mucinous adenocarcinoma with pStage I, should be considered candidates for postoperative adjuvant therapy.

from Cancer via ola Kala on Inoreader http://ift.tt/2oT5rVl
via IFTTT