The impact of an educational tool in cervix image registration across three imaging modalities.

OBJECTIVES: Accurate image registration is vital in cervical cancer where changes in both planning target volume (PTV) and organs at risk (OARs) can make decisions regarding image registration complicated. This work aims to determine the impact of a dedicated educational tool compared with experience gained in MR-guided radiotherapy (MRgRT). METHODS: 10 therapeutic radiographers acted as observers and were split into two groups based on previous experience with MRgRT and Monaco treatment planning system. Three CBCT-CT, three MR-CT and two MR-MR registrations were completed per patient by each observer. Observers recorded translations, time to complete image registration and confidence. Data were collected in two phases; prior to and following the introduction of a cervix registration guide. RESULTS: No statistically significant differences were noted between imaging modalities. Each group was assessed independently pre- and post-education, no statistically significant differences were noted in either CBCT-CT or MR-CT imaging. Group 1 MR-MR imaging showed a statistically significant reduction in interobserver variability (p=0.04), in Group 2, the result was not statistically significant (p=0.06). Statistically significant increases in confidence were seen in all three modalities (p≤0.05). CONCLUSIONS: At The Christie NHS Foundation Trust, radiographers consistently registered images across three different imaging modalities regardless of their previous experience. The implementation of an image registration guide had limited impact on inter- and intraobserver variability. Radiographers' confidence showed statistically significant improvements following the use of the registration manual. ADVANCES IN KNOWLEDGE: This work helps evaluate training methods for novel roles that are developing in MRgRT.

Evaluation of the palliative radiotherapy pathway in a single institute: Can an MR Linac improve efficiency?

BACKGROUND: Palliative radiotherapy (RT) is effectively used to relieve cancer related symptoms. The demand for these services is increasing worldwide. Rapid response clinics have been developed as a means to streamline the palliative RT radiotherapy process and increase efficiency and improve patient experiences. Key components to successful rapid response palliative RT are access to care, streamlined services and innovation. To successfully implement a rapid response RT programme, it is essential to identify gaps between currently provided care and ideal or enhanced care. The aims of this work are to audit the current palliative RT workflow at our institution both prior to and during the coronavirus pandemic. This work reports the impact of covid-19 on rate of palliative RT referrals and proposes a radiographer led, MR guided rapid response workflow to reduce wait times METHODS: A retrospective audit of palliative radiotherapy booking forms was completed over a two yearperiod (2019-2020) to assess the current pathway both prior to and during the covid-19 pandemic. This audit identified patients who had received urgent/emergency spinal RT in the specified timeframe. Further data on these patients was collected using departmental oncology information systems to form a detailed analysis of the pathway and wait times. Data was recorded and analysed using Microsoft Excel. RESULTS: A total of 813 patients met the inclusion criteria for this audit. Data was reported for 2019 and 2020 separately to determine any significant impact caused by the covid-19 pandemic. In 2020 there was an 11.5% increase in referrals for palliative radiotherapy with an equal portion (81%) of total referrals in each year being for single fractions. Timelines from referral to treatment delivery were reported, with those patients receiving same day single fraction RT palliative radiotherapy undergoing further analysis to determine the amount of time spent in the department. Mean wait time for these patients was 5 hours and 20 minutes in 2019 but increased by 20.9% in 2020. CONCLUSIONS: The increasing demand for palliative RT due to rising global cancer rates and extended life expectancy due to advanced systemic treatments may lead to increased wait times. An increase in both referrals and mean wait time was seen during the covid-19 pandemic. Improving efficiency and access to care is essential for this population. The MR Linac could play a role in streamlining palliative RT workflows due to its ability to employ a scan, plan and treat model in a single session. This work forms preliminary support for the development of a trial one stop palliative program on the MR Linac.

Dose-response curve slope sets class-specific limits on inhibitory potential of anti-HIV drugs.

Highly active antiretroviral therapy (HAART) can control HIV-1 replication, but suboptimal treatment allows for the evolution of resistance and rebound viremia. A comparative measure of antiviral activity under clinically relevant conditions would guide drug development and the selection of regimens that maximally suppress replication. Here we show that current measures of antiviral activity, including IC(50) and inhibitory quotient, neglect a key dimension, the dose-response curve slope. Using infectivity assays with wide dynamic range, we show that this slope has noteworthy effects on antiviral activity. Slope values are class specific for antiviral drugs and define intrinsic limitations on antiviral activity for some classes. Nucleoside reverse transcriptase inhibitors and integrase inhibitors have slopes of approximately 1, characteristic of noncooperative reactions, whereas non-nucleoside reverse transcriptase inhibitors, protease inhibitors and fusion inhibitors unexpectedly show slopes >1. Instantaneous inhibitory potential (IIP), the log reduction in single-round infectivity at clinical drug concentrations, is strongly influenced by slope and varies by >8 logs for anti-HIV drugs. IIP provides a more accurate measure of antiviral activity and in general correlates with clinical outcomes. Only agents with slopes >1 achieve high-level inhibition of single-round infectivity, a finding with profound implications for drug and vaccine development.

Stability of the latent reservoir for HIV-1 in patients receiving valproic acid.

In light of a recent report that short-term treatment with valproic acid (VA) might accelerate the decay of the latent reservoir for HIV-1 in patients receiving combination therapy and allow eventual eradication of the infection, we studied patients with prolonged suppression of viremia who were receiving combination therapy and who had also been receiving chronic VA therapy for neurological or psychiatric conditions. Latently infected cells were readily detected in all patients at levels comparable to those seen in patients receiving combination therapy alone. We conclude that the clinical use of VA has no ancillary effect on the decay of the latent reservoir.

The latent reservoir for HIV-1 in resting CD4+ T cells and other viral reservoirs during chronic infection: insights from treatment and treatment-interruption trials.

PURPOSE OF REVIEW: Although treatment of HIV-1 infection with highly active antiretroviral therapy can decrease virus in the plasma to undetectable levels, it cannot eradicate the infection due to the existence of viral reservoirs. These reservoirs are cell types or anatomic sites in which replication-competent virus persists without significant decay over time. This article reviews several proposed reservoirs for HIV-1 and their clinical significance. RECENT FINDINGS: Recent advances allow formal genetic delineation of viral reservoirs and compartments. The best-understood reservoir is a small pool of resting memory CD4 T cells carrying a quiescent form of the HIV-1 genome integrated within active cellular genes. Turnover of these cells is extremely slow, consistent with their function in immunologic memory. Latently infected memory CD4 cells that become reactivated release replication-competent HIV-1 which can be detected in the plasma and which can restore high levels of viremia if treatment is stopped. This reservoir can store drug-resistant virus if it arises, thereby permanently limiting treatment options. Evidence for other cellular reservoirs, including monocytes and macrophages, and for anatomical reservoirs including the genital tract and the central nervous system, is also discussed. SUMMARY: Recent advances in characterizing cellular and anatomic reservoirs and compartments influence approaches to antiretroviral treatment, the management of antiretroviral resistance, and potential eradication strategies. The study of long-lived viral reservoirs is critical to the understanding of chronic HIV-1 infection and to the ongoing search for a cure.