New Antiretroviral Treatment for HIV.

The Joint United Nations Programme on HIV/AIDS (UNAIDS) has set the global goal of ending the AIDS world epidemic by 2030. In order to end this epidemic they have established a 90-90-90 goal to be achieved by 2020, which may be problematic, especially in low- and middle-income countries. This goal includes 90% of individuals with HIV globally being diagnosed, on treatment, and virologically suppressed. Based on global estimates from 2014-2015, approximately 36.9 million individuals are living with HIV. Of those, 53% have been diagnosed with HIV, 41% are on antiretroviral therapy (ART), and 32% have viral suppression with <1000 copies/ml. Comprehensive approaches are needed to improve the number of people living with HIV (PLWH) who are diagnosed, linked, and engaged in care. Once PLWH are retained in care, treatment is key to both HIV prevention and transmission. The development and advancement of new ART is necessary to assist in reaching these goals by improving safety profiles, decreasing pill burden, improving quality of life and life expectancy, and creating new mechanisms to overcome resistance. The focus of this review is to highlight and review data for antiretroviral agents recently added to the market as well as discuss agents in various stages of development (new formulations and mechanisms of action).

Consensus Guidelines and Contouring Atlas for Pelvic Node Delineation in Prostate and Pelvic Node Intensity Modulated Radiation Therapy.

PURPOSE: The purpose of this study was to establish reproducible guidelines for delineating the clinical target volume (CTV) of the pelvic lymph nodes (LN) by combining the freehand Royal Marsden Hospital (RMH) and Radiation Therapy Oncology Group (RTOG) vascular expansion techniques. METHODS AND MATERIALS: Seven patients with prostate cancer underwent standard planning computed tomography scanning. Four different CTVs (RMH, RTOG, modified RTOG, and Prostate and pelvIs Versus prOsTate Alone treatment for Locally advanced prostate cancer [PIVOTAL] trial) were created for each patient, and 6 different bowel expansion margins (BEM) were created to assess bowel avoidance by the CTV. The resulting CTVs were compared visually and by using Jaccard conformity indices. The volume of overlap between bowel and planning target volume (PTV) was measured to aid selection of an appropriate BEM to enable maximal LN yet minimal normal tissue coverage. RESULTS: In total, 84 nodal contours were evaluated. LN coverage was similar in all groups, with all of the vascular-expansion techniques (RTOG, modified RTOG, and PIVOTAL), resulting in larger CTVs than that of the RMH technique (mean volumes: 287.3 cm(3), 326.7 cm(3), 310.3 cm(3), and 256.7 cm(3), respectively). Mean volumes of bowel within the modified RTOG PTV were 19.5 cm(3) (with 0 mm BEM), 17.4 cm(3) (1-mm BEM), 10.8 cm(3) (2-mm BEM), 6.9 cm(3) (3-mm BEM), 5.0 cm(3) (4-mm BEM), and 1.4 cm(3) (5-mm BEM) in comparison with an overlap of 9.2 cm(3) seen using the RMH technique. Evaluation of conformity between LN-CTVs from each technique revealed similar volumes and coverage. CONCLUSIONS: Vascular expansion techniques result in larger LN-CTVs than the freehand RMH technique. Because the RMH technique is supported by phase 1 and 2 trial safety data, we proposed modifications to the RTOG technique, including the addition of a 3-mm BEM, which resulted in LN-CTV coverage similar to that of the RMH technique, with reduction in bowel and planning target volume overlap. On the basis of these findings, recommended guidelines including a detailed pelvic LN contouring atlas have been produced and implemented in the PIVOTAL trial.

Biology of colorectal pulmonary metastasis: implications for surgical resection.

In colorectal cancer, little high grade evidence for cure, life extension, disease modification or palliation achieved by pulmonary metastasectomy exists. This has prompted the pulmonary metastasectomy in colorectal cancer (PulMiCC) trial. Reappraisal of the biological facts on colorectal metastasis may, however, shed light on an alternative avenue of clinical management. Early onset of metastasis, short doubling time and a short disease-free interval are all associated with poor clinical outcomes. Selecting who will be cured (i.e. no occult metastasis) remains the holy grail for pulmonary metastasectomy surgery. Serial CT scans can be utilized to calculate the tumour doubling time by volumetric analysis. Knowing the doubling time and size of the largest metastasis, which by definition is the first cell that has successfully spread from the primary site, the time of initial metastasis can be predicted. More importantly, using the doubling time, calculating the time interval from the primary surgery to the point at which all pulmonary metastases are visible should be possible. Perhaps watchful waiting, with interval CT scanning, followed by pulmonary metastasectomy should be utilized, rather than clinical opinion or randomization in a trial based upon first presentation.