Phase 2 Neoadjuvant Treatment Intensification Trials in Rectal Cancer: A Systematic Review

Purpose: Multiple phase 2 trials of neoadjuvant treatment intensification in locally advanced rectal cancer have reported promising efficacy signals, but these have not translated into improved cancer outcomes in phase 3 trials. Improvements in phase 2 trial design are needed to reduce these false-positive signals. This systematic review evaluated the design of phase 2 trials of neoadjuvant long-course radiation or chemoradiation therapy treatment intensification in locally advanced rectal cancer. Methods and Materials: The PubMed, EMBASE, MEDLINE, and Cochrane Library databases were searched for published phase 2 trials of neoadjuvant treatment intensification from 2004 to 2016. Trial clinical design and outcomes were assessed, with statistical design and compliance rated using a previously published system. Multivariable meta-regression analysis of pathologic complete response (pCR) was conducted. Results: We identified 92 eligible trials. Patients with American Joint Committee on Cancer stage II and III equivalent disease were eligible in 87 trials (94.6%). In 43 trials (46.7%), local staging on magnetic resonance imaging was mandated. Only 12 trials (13.0%) were randomized, with 8 having a standard-treatment control arm. Just 51 trials (55.4%) described their statistical design, with 21 trials (22.8%) failing to report their sample size derivation. Most trials (n=84, 91.3%) defined a primary endpoint, but 15 different primary endpoints were used. All trials reported pCR rates. Only 38 trials (41.3%) adequately reported trial statistical design and compliance. Meta-analysis revealed a pooled pCR rate of 17.5% (95% confidence interval, 15.7%-19.4%) across treatment arms of neoadjuvant long-course radiation or chemoradiation therapy treatment intensification and substantial heterogeneity among the reported effect sizes (I2 = 55.3%, P<.001). Multivariable meta-regression analysis suggested increased pCR rates with higher radiation therapy doses (adjusted P=.025). Conclusions: Improvement in the design of future phase 2 rectal cancer trials is urgently required. A significant increase in randomized trials is essential to overcome selection bias and determine novel schedules suitable for phase 3 testing. This systematic review provides key recommendations to guide future treatment intensification trial design in rectal cancer

What Influences Travellers’ Adoption of a Location-based Social Media Service for Their Travel Planning?

Advances in location-acquisition and mobile communication technologies have empowered people to use location data with online social networks known as location-based social media. However, the technology is relatively new, and literature on the relevant factors determining location-based social media adoption and usage for the specific purpose of travel planning is sparse. Using the Unified Theory of Acceptance and Use of Technology 2 (UTAUT2) as a base model, we extended the model by including users’ mobile Internet experience and the Information Adoption Model in the context of location-based social media adoption and use for travel planning. Data was collected from 200 Chinese respondents and partial least square was employed to test the research model. Our results showed that our model was able to explain about 64% of variance in intention and 48% in location-based social media use in travel planning. We found that besides variables from UTAUT2, argument strength, review rating, reviewer trustworthiness, reviewer expertise and review sidedness can influence users’ adoption of online reviews, which in turn will influence their use of location-based social media. The results of this study will be useful for location-based social media providers in formulating appropriate marketing strategies, as well as developing applications that will attract more users

Difficulty in the induction of tolerance to vascularised skin allografts

Transplantation Proceedings2641957TRPP

Impact of increasing doses of flavonoid-rich and flavonoid-poor fruits and vegetables on antioxidant status in humans – FLAVURS study

The Publisher's final version can be found by following the DOI link

Architecture of population-differentiated polymorphisms in the human genome

10.1371/journal.pone.0224089PLoS ONE1410e022408

Combination of the ERK inhibitor AZD6244 and low-dose sorafenib in a xenograft model of human renal cell carcinoma

10.3892/ijo.2012.1494International Journal of Oncology412712-72