Morpho-molecular signal correlation between optical coherence tomography and Raman spectroscopy for superior image interpretation and clinical diagnosis

The combination of manifold optical imaging modalities resulting in multimodal optical systems allows to discover a larger number of biomarkers than using a single modality. The goal of multimodal imaging systems is to increase the diagnostic performance through the combination of complementary modalities, e.g. optical coherence tomography (OCT) and Raman spectroscopy (RS). The physical signal origins of OCT and RS are distinctly different, i.e. in OCT it is elastic back scattering of photons, due to a change in refractive index, while in RS it is the inelastic scattering between photons and molecules. Despite those diverse characteristics both modalities are also linked via scattering properties and molecular composition of tissue. Here, we investigate for the first time the relation of co-registered OCT and RS signals of human bladder tissue, to demonstrate that the signals of these complementary modalities are inherently intertwined, enabling a direct but more importantly improved interpretation and better understanding of the other modality. This work demonstrates that the benefit for using two complementary imaging approaches is, not only the increased diagnostic value, but the increased information and better understanding of the signal origins of both modalities. This evaluation confirms the advantages for using multimodal imaging systems and also paves the way for significant further improved understanding and clinically interpretation of both modalities in the future

Non-muscle-invasive bladder cancer: a vision for the future

The management of non-muscle-invasive bladder cancer (NMIBC) has evolved from the first reports on bladder endoscopy and transurethral resection to the introduction of adjuvant intravesical treatment. However, disease recurrence and progression remain an ongoing risk, placing a heavy burden on healthcare resources and on patients' quality of life. Deeper understanding of the molecular basis of the disease and developments in optics, lasers and computer science are already offering opportunities to revolutionize care and improve long-term prognosis. This article discusses developments likely to cause a paradigm shift towards the delivery of personalized care and reduced burden of disease in NMIBC

Improved overall survival after implementation of targeted therapy for patients with metastatic renal cell carcinoma: Results from the Danish Renal Cancer Group (DARENCA) study-2

AbstractAimTo evaluate the implementation of targeted therapy on overall survival (OS) in a complete national cohort of patients with metastatic renal cell carcinoma (mRCC).MethodsAll Danish patients with mRCC referred for first line treatment with immunotherapy, TKIs or mTOR-inhibitors between 2006 and 2010 were included. Baseline and outcome data were collected retrospectively. Prognostics factors were identified using log-rank tests and Cox proportional hazard model. Differences in distributions were tested with the Chi-square test.Results1049 patients were referred; 744 patients received first line treatment. From 2006 to 2010 we observed a significant increase in the number of referred patients; a significant increase in treated patients (64% versus 75%, P=0.0188); a significant increase in first line targeted therapy (22% versus 75%, P<0.0001); a significant increase in second line treatment (20% versus 40%, P=0.0104), a significant increased median OS (11.5 versus 17.2 months, P=0.0435) whereas survival for untreated patients remained unchanged. Multivariate analysis validated known prognostic factors. Moreover, treatment start years 2008 (HR 0.74, 95% CI, 0.55–0.99; P=0.0415), 2009 (HR 0.72, 95% CI, 0.54–0.96; P=0.0277) and 2010 (HR 0.63, 95% CI, 0.47–0.86; P=0.0035) compared to 2006, and more than two treatment lines received for patients with performance status 0–1 (HR 0.76, 95% CI, 0.58–0.99; P=0.0397) and performance status 2–3 (HR 0.19, 95% CI, 0.06–0.60; P=0.0051) were significantly associated with longer OS.ConclusionThis retrospective study documents that the implementation of targeted therapy has resulted in significantly improved treatment rates and overall survival in a complete national cohort of treated mRCC patients

Exploration of two methods for quantitative Mitomycin C measurement in tumor tissue in vitro and in vivo

Two methods of quantifying Mitomycin C in tumor tissue are explored. A method of ultraviolet-visible absorption microscopy is developed and applied to measure the concentration of Mitomycin C in preserved mouse tumor tissue, as well as in gelatin samples. Concentrations as low as 60 μM can be resolved using this technique in samples that do not strongly scatter light. A novel method for monitoring the Mitomycin C concentrations inside a tumor is developed, based on microdialysis and ultraviolet-visible spectroscopy. A pump is used to perfuse a microdialysis probe with Ringer’s solution, which is fed to a flow cell to determine intratumor concentrations in real time to within a few μM. The success and limitations of these techniques are identified, and suggestions are made as to further development. To the authors’ knowledge these are the first attempts made to quantify Mitomycin C concentrations in tumor tissue

Adjuvant Sorafenib for Renal Cell Carcinoma at Intermediate or High Risk of Relapse: Results From the SORCE Randomized Phase III Intergroup Trial.

PURPOSE: SORCE is an international, randomized, double-blind, three-arm trial of sorafenib after surgical excision of primary renal cell carcinoma (RCC) found to be at intermediate or high risk of recurrence. PATIENTS AND METHODS: We randomly assigned participants (2:3:3) to 3 years of placebo (arm A), 1 year of sorafenib followed by 2 years of placebo (arm B), or 3 years of sorafenib (arm C). The initial sorafenib dose was 400 mg twice per day orally, amended to 400 mg daily. The primary outcome analysis, which was revised as a result of external results, was investigator-reported disease-free survival (DFS) comparing 3 years of sorafenib versus placebo. RESULTS: Between July 2007 and April 2013, we randomly assigned 1,711 participants (430, 642, and 639 participants in arms A, B, and C, respectively). Median age was 58 years, 71% of patients were men, 84% had clear cell histology, 53% were at intermediate risk of recurrence, and 47% were at high risk of recurrence. We observed no differences in DFS or overall survival in all randomly assigned patients, patients with high risk of recurrence, or patients with clear cell RCC only. Median DFS was not reached for 3 years of sorafenib or for placebo (hazard ratio, 1.01; 95% CI, 0.83 to 1.23; P = .95). We observed nonproportional hazards; the restricted mean survival time (RMST) was 6.81 years for 3 years of sorafenib and 6.82 years for placebo (RMST difference, 0.01 year; 95% CI, -0.49 to 0.48 year; P = .99). Despite offering treatment adaptations, more than half of participants stopped treatment by 12 months. Grade 3 hand-foot skin reaction was reported in 24% of participants on sorafenib. CONCLUSION: Sorafenib should not be used as adjuvant therapy for RCC. Active surveillance remains the standard of care for patients at intermediate or high risk of recurrence after nephrectomy and is the appropriate control of our current international adjuvant RCC trial, RAMPART.CRU