Residual tumor volume and patient survival following reoperation for recurrent glioblastoma.

OBJECTIVES: Maximal safe tumor resection is part of the standard of care for patients with newly diagnosed glioblastoma. The role of reoperation in the care of patients with recurrent glioblastoma is less clear, and less than a quarter of patients undergo a second surgery. Previous studies have identified preoperative variables associated with the improved survival of patients following reoperation, and guidelines for the selection of patients for reoperation have been devised and validated. In this study, the authors analyzed the relative survival benefit of maximal safe tumor removal in a series of patients with recurrent glioblastoma who all underwent reoperation. METHODS: In this longitudinal study, the clinical and radiological data of 97 consecutive patients who underwent reoperation for recurrent glioblastoma were prospectively collected. Multiple regression analyses and Kaplan-Meier plotting were performed to identify pre- and postoperative clinical and radiological variables associated with increased survival following reoperation. RESULTS: The median postoperative survival of all patients following reoperation was 12.4 months (95% confidence interval [CI] 9.0-15.6 months). Multiple Cox regression analysis revealed that patients with large (> 3 cm(3)) residual tumors following reoperation had significantly decreased survival relative to those with residual tumors that were small (> 0-3 cm(3); hazard ratio [HR] = 3.10, 95% CI 1.69-5.70; p < 0.001) or radiologically absent (0 cm(3); HR = 5.82, 95% CI 2.98-11.37; p < 0.001). Large residual tumors had faster rates of subsequent regrowth than small (odds ratio [OR] = 4.22, 95% CI 1.19-14.97; p = 0.026) or radiologically absent (OR = 11.00, 95% CI 2.79-43.43; p = 0.001) residual tumors, and a faster regrowth rate was significantly associated with decreased survival (HR = 4.01, 95% CI 2.26-7.14; p < 0.001). CONCLUSIONS: The overall survival of patients with recurrent glioblastoma who underwent reoperations increased with decreasing postoperative residual tumor volumes. For patients meeting prognostic criteria for reoperation, the surgical goal should be to minimize residual tumor volume to maximize overall survival. Clinical trial registration no.: NCT00060541 ( ClinicalTrials.gov ).

The impact of age on colorectal cancer incidence, treatment, and outcomes in an equal-access health care system.

BACKGROUND: Inferior outcomes in younger patients with colorectal cancer may be associated with multiple factors, including tumor biology, delayed diagnosis, disparities such as access to care, and/or treatment differences. OBJECTIVE: This study aims to examine age-based colorectal cancer outcomes in an equal-access health care system. DESIGN: This study is a retrospective large multi-institutional database analysis. PATIENTS: Patients with colorectal cancer included in the Department of Defense Automated Central Tumor Registry (January 1993 to December 2008) were stratified by age <40, 40 to 49, 50 to 79, and ≥80 years to determine the effect of age on incidence, treatment, and outcomes. MAIN OUTCOME MEASURES: The primary outcomes measured were the stage at presentation, adjuvant therapy use, 3- and 5-year disease-free survival, and overall survival. RESULTS: Some 7948 patients were identified; most (77%) patients were in the 50- to 79-year age group. Overall, 25% presented with stage III disease. Compared with patients aged 50 to 79 and ≥80 years, patients aged <40 and 40 to 49 years presented more frequently with advanced disease (stage III (35% and 35% vs 28% and 26%) and stage IV (24% and 21% vs 18% and 15%); all p < 0.001). Adjuvant chemotherapy use in stage III patients was 62%; those patients ≥80 and 50 to 79 years had decreased use (p < 0.001). Overall recurrence was 8.1% at 3 years and 9.7% at 5 years, with the highest rates in patients <40 years (11.8%; p = 0.007). Overall survival was worse in patients ≥80 years, whereas the remaining cohorts were similar. For stage III disease, patients 40 to 49 years had the highest survival among all cohorts (p < 0.001). LIMITATIONS: This study was limited by the lack of specific comorbid information and the limitations inherent to large database reviews. CONCLUSIONS: In an equal-access system, young age at presentation (<50 years) was associated with advanced stage and higher recurrence of colorectal cancer, but similar survival in comparison with older patients. Although increased adjuvant therapy use in younger patients may partially account for stage-specific increases in survival, the relative decreased chemotherapy use overall requires further evaluation.

Scale to predict survival after surgery for recurrent glioblastoma multiforme.

PURPOSE: Despite initial treatment with surgical resection, radiotherapy, and chemotherapy, glioblastoma multiforme (GBM) virtually always recurs. Surgery is sometimes recommended to treat recurrence. In this study, we sought to devise a preoperative scale that predicts survival after surgery for recurrent glioblastoma multiforme. PATIENTS AND METHODS: The preoperative clinical and radiographic data of 34 patients who underwent re-operation of recurrent GBM tumors were analyzed using Kaplan-Meier survival analysis and Cox proportional hazards regression modeling. The factors associated with decreased postoperative survival (P < .05) were used to devise a prognostic scale which was validated with a separate cohort of 109 patients. RESULTS: The factors associated with poor postoperative survival were: tumor involvement of prespecified eloquent/critical brain regions (P = .021), Karnofsky performance status (KPS) < or = 80 (P = .030), and tumor volume > or = 50 cm(3) (P = .048). An additive scale (range, 0 to 3 points) comprised of these three variables distinguishes patients with good (0 points), intermediate (1 to 2 points), and poor (3 points) postoperative survival (median survival, 10.8, 4.5, and 1.0 months, respectively; P < .001). The scale identified three statistically distinct groups within the validation cohort as well (median survival, 9.2, 6.3, and 1.9 months, respectively; P < .001). CONCLUSION: We devised and validated a preoperative scale that identifies patients likely to have poor, intermediate, and good relative outcomes after surgical resection of a recurrent GBM tumor. Application of this simple scale may be useful in counseling patients regarding their treatment options and in designing clinical trials.

Experimental approaches for the treatment of malignant gliomas.

Malignant gliomas, which include glioblastomas and anaplastic astrocytomas, are the most common primary tumors of the brain. Over the past 30 years, the standard treatment for these tumors has evolved to include maximal safe surgical resection, radiation therapy and temozolomide chemotherapy. While the median survival of patients with glioblastomas has improved from 6 months to 14.6 months, these tumors continue to be lethal for the vast majority of patients. There has, however, been recent substantial progress in our mechanistic understanding of tumor development and growth. The translation of these genetic, epigenetic and biochemical findings into therapies that have been tested in clinical trials is the subject of this review.

Enhanced chondrocyte densities on carbon nanotube composites: the combined role of nanosurface roughness and electrical stimulation.

Simultaneous incorporation of intrinsic nanosurface roughness and external electrical stimulation may maximize the regeneration of articular cartilage tissue more than on nanosmooth, electrically nonstimulated biomaterials. Here, we report enhanced functions of chondrocytes (cartilage synthesizing cells) on electrically and nonelectrically stimulated highly dispersed carbon nanotubes (CNT) in polycarbonate urethane (PCU) compared to, respectively, stimulated pure PCU. Specifically, compared to conventional longitudinal (or vertical) electrical stimulation of chondrocytes on conducting surfaces which require high voltage, we developed a lateral electrical stimulation across CNT/PCU composite films of low voltage that enhanced chondrocyte functions. Chondrocyte adhesion and long-term cell densities (up to 2 days) were enhanced (more than 50%) on CNT/PCU composites compared to PCU alone without electrical stimulation. This study further explained why by measuring greater amounts of initial fibronectin adsorption (a key protein that mediates chondrocyte adhesion) on CNT/PCU composites which were more hydrophilic (than pure PCU) due to greater nanometer roughness. Importantly, the same trend was observed and was even significantly enhanced when chondrocytes were subjected to electrical stimulation (more than 200%) compared to nonstimulated CNT/PCU. For this reason, this study provided direct evidence of the positive role that conductive CNT/PCU films can play in promoting functions of chondrocytes for cartilage regeneration.

Accelerated chondrocyte functions on NaOH-treated PLGA scaffolds.

Compared to conventional poly(lactic-co-glycolic acid) (PLGA), previous studies have shown that NaOH-treated PLGA two-dimensional substrates enhanced functions of osteoblasts (bone-forming cells), vascular and bladder smooth muscle cells, and chondrocytes (cartilage-synthesizing cells). In this same spirit, the purpose of this in vitro study was to fabricate three-dimensional NaOH-treated PLGA scaffolds and determine their efficacy toward articular cartilage applications. To improve functions of chondrocytes including their adhesion, growth, differentiation, and extracellular matrix synthesis, PLGA scaffolds were modified via chemical etching techniques using 1N NaOH for 10 min. Results demonstrated that NaOH-treated PLGA three-dimensional scaffolds enhanced chondrocyte functions compared to non-treated scaffolds. Specifically, chondrocyte numbers, total intracellular protein content, and the amount of extracellular matrix components (such as glycosaminoglycans and collagens) were significantly greater on NaOH-treated than on non-treated PLGA scaffolds. Underlying material properties that may have enhanced chondrocyte functions include a more hydrophilic surface (due to hydrolytic degradation of PLGA by NaOH), increased surface area, altered porosity (both percent and diameter of individual pores), and a greater degree of nanometer roughness. For these reasons, this study adds a novel tissue-engineering scaffold to the cartilage biomaterial community: NaOH-treated PLGA. Clearly, such modifications to PLGA may ultimately enhance the efficacy of tissue-engineering scaffolds for articular cartilage repair.