Oxygen depleted hypoxic regions in the tumour are generally resistant to therapies1. Although nanocarriers have been used to deliver drugs, the targeting ratios have been very low. Here, we show that the magneto-aerotactic migration behaviour2 of magnetotactic bacteria3, Magnetococcus marinus strain MC-14, can be used to transport drug-loaded nanoliposomes into hypoxic regions of the tumour. In their natural environment, MC-1 cells, each containing a chain of magnetic iron-oxide nanocrystals5, tend to swim along local magnetic field lines and towards low oxygen concentrations6 based on a two-state aerotactic sensing system2. We show that when MC-1 cells bearing covalently bound drug-containing nanoliposomes were injected near the tumour in SCID Beige mice and magnetically guided, up to 55% of MC-1 cells penetrated into hypoxic regions of HCT116 colorectal xenografts. Approximately 70 drug-loaded nanoliposomes were attached to each MC-1 cell. Our results suggest that harnessing swarms of microorganisms exhibiting magneto-aerotactic behaviour can significantly improve the therapeutic index of various nanocarriers in tumour hypoxic regions.

Radiotherapy has been driven by constant technological advances since the discovery of X-rays in 1895. Radiotherapy aims to sculpt the optimal isodose on the tumour volume while sparing normal tissues. The benefits are threefold: patient cure, organ preservation and cost-efficiency. The efficacy and tolerance of radiotherapy were demonstrated by randomized trials in many different types of cancer (including breast, prostate and rectum) with a high level of scientific evidence. Such achievements, of major importance for the quality of life of patients, have been fostered during the past decade by linear accelerators with computer-assisted technology. More recently, these developments were augmented by proton and particle beam radiotherapy, usually combined with surgery and medical treatment in a multidisciplinary and personalized strategy against cancer. This article reviews the timeline of 100 years of radiotherapy with a focus on breakthroughs in the physics of radiotherapy and technology during the past two decades, and the associated clinical benefits.

Megavoltage x-ray beams exhibit the well-known phenomena of dose buildup within the first few millimeters of the incident phantom surface, or the skin. Results of the surface dose measurements, however, depend vastly on the measurement technique employed. Our goal in this study was to determine a correction procedure in order to obtain an accurate skin dose estimate at the clinically relevant depth based on radiochromic film measurements. To illustrate this correction, we have used as a reference point a depth of 70 micron. We used the new GAFCHROMIC dosimetry films (HS, XR-T, and EBT) that have effective points of measurement at depths slightly larger than 70 micron. In addition to films, we also used an Attix parallel-plate chamber and a home-built extrapolation chamber to cover tissue-equivalent depths in the range from 4 micron to 1 mm of water-equivalent depth. Our measurements suggest that within the first millimeter of the skin region, the PDD for a 6 MV photon beam and field size of 10 x 10 cm2 increases from 14% to 43%. For the three GAFCHROMIC dosimetry film models, the 6 MV beam entrance skin dose measurement corrections due to their effective point of measurement are as follows: 15% for the EBT, 15% for the HS, and 16% for the XR-T model GAFCHROMIC films. The correction factors for the exit skin dose due to the build-down region are negligible. There is a small field size dependence for the entrance skin dose correction factor when using the EBT GAFCHROMIC film model. Finally, a procedure that uses EBT model GAFCHROMIC film for an accurate measurement of the skin dose in a parallel-opposed pair 6 MV photon beam arrangement is described.

Background:Pathological extramural vascular invasion (EMVI) is an independent prognostic factor in rectal cancer, but can also be identified on MRI-detected extramural vascular invasion (mrEMVI). We perform a meta-analysis to determine the risk of metastatic disease at presentation and after surgery in mrEMVI-positive patients compared with negative tumours.Methods:Electronic databases were searched from January 1980 to March 2016. Conventional meta-analytical techniques were used to provide a summative outcome. Quality assessment of the studies was performed.Results:Six articles reported on mrEMVI in 1262 patients. There were 403 patients in the mrEMVI-positive group and 859 patients in the mrEMVI-negative group. The combined prevalence of mrEMVI-positive tumours was 0.346(range=0.198–0.574). Patients with mrEMVI-positive tumours presented more frequently with metastases compared to mrEMVI-negative tumours (fixed effects model: odds ratio (OR)=5.68, 95% confidence interval (CI) (3.75, 8.61), z=8.21, df=2, P<0.001). Patients who were mrEMVI-positive developed metastases more frequently during follow-up (random effects model: OR=3.91, 95% CI (2.61, 5.86), z=6.63, df=5, P<0.001).Conclusions:MRI-detected extramural vascular invasion is prevalent in one-third of patients with rectal cancer. MRI-detected extramural vascular invasion is a poor prognostic factor as evidenced by the five-fold increased rate of synchronous metastases, and almost four-fold ongoing risk of developing metastases in follow-up after surgery.

Aim Low anterior resection syndrome (LARS) is pragmatically defined as disordered bowel function after rectal resection leading to a detriment in quality of life. This broad characterization does not allow for precise estimates of prevalence. The LARS score was designed as a simple tool for clinical evaluation of LARS. Although the LARS score has good clinical utility, it may not capture all important aspects that patients may experience. The aim of this collaboration was to develop an international consensus definition of LARS that encompasses all aspects of the condition and is informed by all stakeholders. Method This international patient–provider initiative used an online Delphi survey, regional patient consultation meetings, and an international consensus meeting. Three expert groups participated: patients, surgeons and other health professionals from five regions (Australasia, Denmark, Spain, Great Britain and Ireland, and North America) and in three languages (English, Spanish, and Danish). The primary outcome measured was the priorities for the definition of LARS. Results Three hundred twenty‐five participants (156 patients) registered. The response rates for successive rounds of the Delphi survey were 86%, 96% and 99%. Eighteen priorities emerged from the Delphi survey. Patient consultation and consensus meetings refined these priorities to eight symptoms and eight consequences that capture essential aspects of the syndrome. Sampling bias may have been present, in particular, in the patient panel because social media was used extensively in recruitment. There was also dominance of the surgical panel at the final consensus meeting despite attempts to mitigate this. Conclusion This is the first definition of LARS developed with direct input from a large international patient panel. The involvement of patients in all phases has ensured that the definition presented encompasses the vital aspects of the patient experience of LARS. The novel separation of symptoms and consequences may enable greater sensitivity to detect changes in LARS over time and with intervention.

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Local excision alone is an acceptable option for well-differentiated, T1 carcinomas, < or = 3 cm. Adjuvant radiation is recommended for T2 lesions. The high local recurrence rate in patients after local excision of T3 lesions with or without adjuvant radiotherapy would mandate a radical resection.