Comparison of four early posttherapy imaging changes (EPTIC; RECIST 1.0, tumor shrinkage, computed tomography tumor density, Choi criteria) in assessing outcome to vascular endothelial growth factor-targeted therapy in patients with advanced renal cell carcinoma

Background

Vascular endothelial growth factor (VEGF)-targeted therapy has become standard treatment for patients with metastatic renal cell cancer (mRCC). Since these therapies can induce tumor necrosis and minimal tumor shrinkage, Response Evaluation Criteria in Solid Tumors (RECIST) may not be optimal for predicting clinical outcome.

Objective

To systematically determine the optimal early posttherapy imaging changes (EPTIC) to separate responders and nonresponders at the first posttreatment follow-up computed tomography (CT).

Design, setting, and participants

Seventy mRCC patients with 155 target lesions treated with first-line sunitinib, sorafenib, or bevacizumab at academic medical centers underwent contrast-enhanced thoracic and abdominal CT at baseline and first follow-up after therapy initiation (median: 78 d after therapy initiation; range: 31–223 d).

Measurements

Evaluations were performed according to (1) RECIST 1.0; (2) Choi criteria; (3) tumor shrinkage (TS) of ≥10% decrease in sum of the longest unidimensional diameter (SLD); and (4) 15% or 20% decrease in mean CT tumor density. Correlation with time to treatment failure (TTF) and overall survival (OS) were compared and stratified by response to each of the radiologic criteria.

Results and limitations

Eleven patients were considered responders by RECIST 1.0; 49 based on Choi criteria; 31 patients had ≥10% decrease in the SLD; and 36 and 32 patients had ≥15% and ≥20% decrease, respectively, in mean tumor density on CT. Only the threshold of 10% decrease in the SLD was statistically significant in predicting TTF (10.4 vs 5.1 mo; p = 0.02) and OS (32.5 vs 15.8 mo; p = 0.002). Receiver operating characteristic analysis yielded a 10% decrease in SLD as the optimal size change threshold for responders. The retrospective nature of the study and measurements by a single oncoradiologist are inherent limitations.

Conclusions

In the retrospectively analyzed study population of mRCC patients receiving VEGF-targeted agents, a 10% reduction in the SLD on the first follow-up CT was an optimal early predictor of outcome.     

The role of race, socioeconomic status, and distance traveled on the outcome of African-American patients with multiple myeloma

The incidence and mortality of multiple myeloma (MM) in African-Americans is double that in whites. We questioned whether race, socioeconomic status, and distance traveled affect overall survival. In a retrospective review of the records of 292 patients with MM. We found that the median age was 60 years and 38 patients were African-Americans. The mean distance traveled was 67.7 miles. The median overall survival was similar in African-Americans and whites. Race, distance traveled and socioeconomic status were not independent prognostic factors for overall survival. In conclusion, socioeconomic status, distance traveled and race did not affect outcomes of MM patients treated at a specialized myeloma center.     

Effects of aging and atherosclerosis on endothelial and vascular smooth muscle function in humans

BACKGROUND: Nitric oxide is an endothelium dependent dilator, which may protect against atherosclerosis. Several studies have shown a decrease in nitric oxide activity with aging, however none have assessed aging and atherosclerosis separately. We tested the hypothesis that aging blunts both basal and receptor-mediated endothelial nitric oxide release in humans. METHODS: We examined whether forearm blood flow responses to intra-arterial acetylcholine, and nitroprusside, were altered with aging, with and without co-infusion of an inhibitor of nitric oxide synthase (N(G)-mono-methyl-L-arginine) in three groups of human subjects; a group with clinical atherosclerotic vascular disease (n = 31, 21 M), otherwise healthy elderly (n = 17, 13 M), and healthy young controls (n = 15, 8 M). RESULTS: There was no difference in basal flows between the three groups. There was also no difference in the dilatation to either acetylcholine or nitroprusside responses between the AVD and the healthy elderly group; however, aging significantly decreased acetylcholine or nitroprusside responses when compared to the young controls (p < 0.02). Furthermore, the ratio between acetylcholine and nitroprusside, a marker of endothelial NO synthase activity, was significantly greater in the young volunteers (0.816 +/- 0.094% vs. 0.892 +/- 0.146 % vs. 1.389 +/- 0.2%, in atherosclerotic vascular disease, healthy elderly group, and young controls respectively). CONCLUSIONS: Forearm blood flow responses to endothelium dependent and independent stimuli are blunted with aging, independent of the presence of atherosclerotic disease. Moreover, the normal aging process may induce significant global vascular dysfunction (involving the endothelium and the vascular smooth muscle); to as great a degree as clinically manifest atherosclerosis.     

10% Tumor Diameter Shrinkage on the First Follow‐Up Computed Tomography Predicts Clinical Outcome in Patients With Advanced Renal Cell Carcinoma Treated With Angiogenesis Inhibitors: A Follow‐Up Validation Study

Background.

Vascular endothelial growth factor (VEGF)-targeted agents are standard therapies for metastatic renal cell carcinoma (mRCC), associated with variable tumor shrinkage. Response Evaluation Criteria in Solid Tumors (RECIST) is of limited utility in this setting, and other imaging changes are sought to reliably predict outcome early. We aim to validate 10% tumor shrinkage as the best early indicator of outcome.

Methods.

In this institutional review board-approved, Health Insurance Portability and Accountability Act-compliant study, 66 mRCC patients with 165 lesions on clinical trials of VEGF-targeted agents underwent thoracic and abdominal computed tomography at baseline and at first follow-up after therapy. Measurements were performed according to RECIST and tumor shrinkage of ≥10% decrease in sum of the longest diameter (−10%SLD). Correlation with time-to-treatment failure (TTF) and overall survival (OS) were compared and stratified by response to the radiologic criteria. Receiver-operating characteristics (ROC) analysis yielded the optimal threshold change in SLD, defining patients with prolonged survival.

Results.

More than −10%SLD significantly differentiated responders from nonresponders (median TTF 8.4 vs. 4.1 months, p = .001), whereas partial response by RECIST did not (median TTF 6.9 vs. 5.5 months in responders vs. nonresponders, p = .34). −10%SLD was also significantly predictive of OS (median OS 35.1 vs. 15.0 months in responders vs. nonresponders, p = .003). ROC curve analysis yielded −9.3% in SLD as the optimal threshold for response/no response.

Conclusion.

Ten percent tumor shrinkage is validated as a reliable early predictor of outcome in mRCC patients receiving VEGF-targeted therapies and may provide a practical measure to guide therapeutic decisions.     

Bacterial indicators of pollution of the Douala lagoon, Cameroon: Public health implications

Background

Indiscriminate disposal of untreated wastes which are often heavily laden with sewage microorganisms some of which are pathogenic to humans into aquatic environments near cities could serve as potential dangers to human health.

Objective

A prospective study was undertaken to investigate the scope of potential bacterial pathogens and to assess the extent of pollution of the Douala lagoon.

Methods

A total of eighty water samples were collected fortnightly from the lagoon at five stations from March to October 2005 and analysed for heterotrophic bacterial densities, coliform counts, faecal coliform and faecal streptococcal counts. Bacteria were isolated and identified using standard microbiology and biochemical techniques.

Results

High heterotrophic bacterial counts (33 × 10⁵ − 161 × 10⁵ CFU/ mL), total coliform counts (1.8 × 10² − 2.4 × 10² CFU/100 mL), faecal coliform counts (2.2 × 10² − 2.4 × 10² CFU/ 100 mL) and faecal streptococcal counts (2.1 × 102 − 2.3 x 10² CFU/100mL were observed in all sampling stations. Eleven species of bacteria: Bacteroides fragilis, Proteus vulgaris, Klebsiella pneumoniae, E. coli, Enterococcus faecalis, Enterobacter aerogenes, Citrobacter freundii, Aeromonas hydrophila, Pseudomonas aeruginosa, Bacillus mycoides and Serratia marcesens, were frequently isolated.

Conclusion

The presence of potential bacterial agents such as Bacteroides fragilis, Pseudomonas aeruginosa, Aeromonas hydrophila, Klebsiella pneumoniae and E. coli in the lagoon may pose a serious threat to the health and well being of users of the Lagoon and calls for urgent intervention.     

Recent advances in immunotherapy for the treatment of prostate cancer

INTRODUCTION: Prostate cancer vaccines attempt to induce cancer-specific systemic immune responses and represent a new class of targeted therapies, many of which are non-toxic. Several vaccine technologies are in development. AREAS COVERED: An autologous antigen presenting cell vaccine loaded with prostate acid phosphatase conjugated with GM-CSF, sipuleucel-T confers a survival advantage in men with metastatic castration-resistant prostate cancer (CRPC) and is now FDA approved based on the IMPACT trial. A poxvirus-based vaccine, PROSTVAC-VF TRICOM targeting prostate-specific antigen (PSA), has demonstrated improved survival in a randomized Phase II trial of patients with metastatic CRPC. Novel T lymphocyte checkpoint inhibitors of cytotoxic T lymphocyte antigen 4 and programmed death-1 are also emerging. Recognition of improved survival without an earlier clinical signal of activity by conventional criteria has led to new guidelines to evaluate immunotherapeutic agents. The clinical benefit of combining vaccines with chemotherapy, radiotherapy and other immunotherapeutic and biologic agents is being evaluated in the context of disappointing results of combination GVAX vaccine and docetaxel chemotherapy. EXPERT OPINION: To build on the success of early phase trials, efforts must be made to optimize vaccine approaches and patient selection.