Magnetic hyperthermia (MH) harnesses the heat‐releasing properties of superparamagnetic iron oxide nanoparticles (SPIONs) and has potential to stimulate immune activation in the tumor microenvironment whilst sparing surrounding normal tissues. To assess feasibility of localized MH in vivo, SPIONs are injected intratumorally and their fate tracked by Zirconium‐89‐positron emission tomography, histological analysis, and electron microscopy. Experiments show that an average of 49% (21–87%, n = 9) of SPIONs are retained within the tumor or immediately surrounding tissue. In situ heating is subsequently generated by exposure to an externally applied alternating magnetic field and monitored by thermal imaging. Tissue response to hyperthermia, measured by immunohistochemical image analysis, reveals specific and localized heat‐shock protein expression following treatment. Tumor growth inhibition is also observed. To evaluate the potential effects of MH on the immune landscape, flow cytometry is used to characterize immune cells from excised tumors and draining lymph nodes. Results show an influx of activated cytotoxic T cells, alongside an increase in proliferating regulatory T cells, following treatment. Complementary changes are found in draining lymph nodes. In conclusion, results indicate that biologically reactive MH is achievable in vivo and can generate localized changes consistent with an anti‐tumor immune response.

Approximately one-third of women diagnosed with melanoma are of child-bearing age. The annual incidence of melanoma has risen steadily over the last 40 years, resulting in increasing numbers of women diagnosed with melanoma both during pregnancy, and post-partum. To date, there are no formal guidelines on the management of pregnancy associated melanoma (PAM), both early stage and metastatic. This article reviews the existing literature and provides a framework for the investigation and multidisciplinary management of PAM.

Ifosfamide is used to treat soft-tissue sarcoma (STS) and bone sarcoma (BS), with improved efficacy at doses above 9 g/m²/cycle. To mitigate treatment-associated toxicity with higher doses, continuous infusional ifosfamide is increasingly used. However, clinical outcome data remain limited. Single-centre retrospective analysis of patients treated with four-weekly infusional ifosfamide (14 g/m²/14d) between August 2012 and February 2019 was conducted. Radiological response, progression-free survival (PFS), overall survival (OS) and toxicity were evaluated. Eighty patients were treated—46 with STS and 34 with BS. Patients received a median of three cycles of infusional ifosfamide (1–24). Overall disease control rate (DCR) in STS was 50% (23 of 46 patients), with a median PFS of 3.8 months, and median OS of 13.0 months. In synovial sarcoma (SS), DCR was 80% (12/15), median PFS 8.1 months and median OS 20.9 months. Overall DCR in BS (34 patients) was 30%, with a median PFS of 2.5 months and median OS of 6.2 months. Five patients (6%) stopped treatment due to toxicity alone within the first two cycles. A further 10 patients stopped treatment due to toxicity during later treatment cycles (12%) and 18 patients (23%) required dose modification. Forty-five patients (56%) experienced grade (G) 3/4 haematological toxicity, with 12 episodes of febrile neutropenia and one treatment-related death. Twenty-seven patients (34%) experienced G3/4 non-haematological toxicity, most commonly nausea and vomiting (10, 13%). In summary, infusional ifosfamide has efficacy in STS, most notable in SS. Benefit appears limited in BS. Treatment is associated with toxicity that requires specialist supportive care.

UK Guidelines for the management of uveal melanoma (UM) were first published in 2015 using an evidence-based systematic approach. The primary aim of this guideline was to optimise patient care by providing recommendations based on the best available scientific evidence. The resulting guideline reflected the strengths and weaknesses of the available evidence, made recommendations that were clinically impactful around prognostication, surveillance, and treatment for patients with primary lesions and metastatic disease. The guideline development process and content met the standards required by NICE and were ultimately NICE accredited. Here, we present an update to these guidelines, highlighting where practice or treatment has changed to such an extent that the original recommendations are now out of date. Presented here are updated guidelines on molecular and genetic testing, management of metastatic disease and clinical surveillance.

Whilst anal cancer accounts for less than 1% of all new cancer cases, incidence rates have increased by up to 70% in the last 30 years with the majority of cases driven by human papilloma virus (HPV) infection. Standard treatment for localised anal cancer is chemoradiotherapy (CRT). Localised progression is the predominant pattern of relapse but well under 50% of cases are salvaged by surgery, predominantly because confirming recurrence within post-radiation change is very challenging. Identifying cancer-associated circulating cells (CCs) in peripheral blood could offer a corroborative method of monitoring treatment efficacy and identifying relapse early. To study this, nucleated cells were isolated from the blood of patients with anal cancer prior to, during, and after CRT and processed through the Amnis^® ImageStream^®X Mk II Imaging Flow Cytometer, without prior enrichment, using Pan-cytokeratin (PCK), CD45 antibodies and making use of the DNA dye DRAQ5. Analysis was undertaken using IDEAS software to identify those cells that were PCK-positive and DRAQ5-positive as well as CD45-negative; these were designated as CCs. CCs were identified in 7 of 8 patients; range 60–876 cells per mL of blood. This first report of the successful identification of CCs in anal cancer patients raises the possibility that liquid biopsies will find a future role as a prognostic/diagnostic tool in this patient group.

Background: A randomised phase II trial demonstrated that the addition of olaratumab to doxorubicin significantly increased overall survival (OS) in patients with advanced soft tissue sarcomas (STS) compared to doxorubicin alone. The recently presented phase III study of doxorubicin and olaratumab in advanced soft tissue sarcoma was discordant with this finding. Methods: We performed a retrospective analysis of adult patients with advanced-/metastatic STS treated with at least two cycles of doxorubicin and olaratumab at eight sarcoma units across England and Northern Ireland between May 2017 and March 2019. Results: 172 patients were evaluable and 40 patients (23.3%) had died at the time of analysis. Median ECOG performance status (PS) was 1. Median progression free survival (PFS) was 6.8 months (95% CI 5.9–7.7 months). Leiomyosarcoma was the most common histological subtype (75 patients, 43.6%), followed by liposarcomas (19, 11.0%). The mean number of cycles was 5 (doxorubicin range 2–6; olaratumab range 2–23). Two patients (1.2%) had a complete response and 34 (19.8%) had a partial response. 79 (45.9%) had stable and 58 (33.7%) progressive disease. 57 patients (33.1%) experienced grade ≥ 3 neutropenia and 7 patients (4.1%) grade ≥ 3 febrile neutropenia. Grade ≥ 3 anaemia was seen in 21 patients (12.2%). Grade ≥ 3 non-haematological toxicities were seen in 35 patients (20.3%). A clinically significant drop in left ventricular ejection fraction was seen in 6 patients (3.5%). 48 patients (27.9%) required a dose reduction. Overall survival (OS) is pending. Conclusions: Our results are in keeping with the phase III study findings: response rate, PFS and OS were similar to those reported in the phase III ANNOUNCE trial.