Intratumoural immunotherapies for unresectable and metastatic melanoma: current status and future perspectives.

The emergence of human intratumoural immunotherapy (HIT-IT) is a major step forward in the management of unresectable melanoma. The direct injection of treatments into melanoma lesions can cause cell lysis and induce a local immune response, and might be associated with a systemic immune response. Directly injecting immunotherapies into tumours achieves a high local concentration of immunostimulatory agent while minimising systemic exposure and, as such, HIT-IT agents are associated with lower toxicity than systemic immune checkpoint inhibitors (CPIs), enabling their potential use in combination with other therapies. Consequently, multiple HIT-IT agents, including oncolytic viruses, pattern-recognition receptor agonists, injected CPIs, cytokines and immune glycolipids, are under investigation. This review considers the current clinical development status of HIT-IT agents as monotherapy and in combination with systemic CPIs, and the practical aspects of administering and assessing the response to these agents. The future of HIT-IT probably lies in its use in combination with systemic CPIs; data from Phase 2 trials indicate a synergy between HIT-IT and CPIs. Data also suggest that the addition of HIT-IT to a CPI might generate responses in CPI-refractory tumours, thereby overcoming resistance and addressing a current unmet need in unresectable and metastatic melanoma for treatment options following progression after CPI treatment

Ice-sheet scale distribution and morphometry of triangular-shaped hummocks (murtoos): a subglacial landform produced during rapid retreat of the Scandinavian Ice Sheet

High-resolution digital elevation models of Finland and Sweden based on LiDAR (Light Detection and Ranging) reveal subglacial landforms in great detail. We describe the ice-sheet scale distribution and morphometric characteristics of a glacial landform that is distinctive in morphology and occurs commonly in the central parts of the former Scandinavian Ice Sheet, especially up-ice of the Younger Dryas end moraine zone. We refer to these triangular or V-shaped landforms as murtoos (singular, ‘murtoo’). Murtoos are typically 30–200 m in length and 30–200 m in width with a relief of commonly <5 m. Murtoos have straight and steep edges, a triangular tip oriented parallel to ice-flow direction, and an asymmetric longitudinal profile with a shorter, but steeper down-ice slope. The spatial distribution of murtoos and their geomorphic relation to other landforms indicate that they formed subglacially during times of climate warming and rapid retreat of the Scandinavian Ice Sheet when large amounts of meltwater were delivered to the bed. Murtoos are formed under warm-based ice and may be associated with a non-channelized subglacial hydraulic system that evacuated large discharges of subglacial water</p

Pain outcomes in patients with bone metastases from advanced cancer: assessment and management with bone-targeting agents

Bone metastases in advanced cancer frequently cause painful complications that impair patient physical activity and negatively affect quality of life. Pain is often underreported and poorly managed in these patients. The most commonly used pain assessment instruments are visual analogue scales, a single-item measure, and the Brief Pain Inventory Questionnaire-Short Form. The World Health Organization analgesic ladder and the Analgesic Quantification Algorithm are used to evaluate analgesic use. Bone-targeting agents, such as denosumab or bisphosphonates, prevent skeletal complications (i.e., radiation to bone, pathologic fractures, surgery to bone, and spinal cord compression) and can also improve pain outcomes in patients with metastatic bone disease. We have reviewed pain outcomes and analgesic use and reported pain data from an integrated analysis of randomized controlled studies of denosumab versus the bisphosphonate zoledronic acid (ZA) in patients with bone metastases from advanced solid tumors. Intravenous bisphosphonates improved pain outcomes in patients with bone metastases from solid tumors. Compared with ZA, denosumab further prevented pain worsening and delayed the need for treatment with strong opioids. In patients with no or mild pain at baseline, denosumab reduced the risk of increasing pain severity and delayed pain worsening along with the time to increased pain interference compared with ZA, suggesting that use of denosumab (with appropriate calcium and vitamin D supplementation) before patients develop bone pain may improve outcomes. These data also support the use of validated pain assessments to optimize treatment and reduce the burden of pain associated with metastatic bone disease

Starting the fight in the tumor: expert recommendations for the development of human intratumoral immunotherapy (HIT-IT).

A European Society for Medical Oncology (ESMO)-sponsored expert meeting was held in Paris on 8 March 2018 which comprised 11 experts from academia, 11 experts from the pharmaceutical industry and 2 clinicians who were representatives of ESMO. The focus of the meeting was exclusively on the intratumoral injection/delivery of immunostimulatory agents with the aim of harmonizing the standard terms and methodologies used in the reporting of human intratumoral immunotherapy (HIT-IT) clinical trials to ensure quality assurance and avoid a blurring of the data reported from different studies. The goal was to provide a reference document, endorsed by the panel members that could provide guidance to clinical investigators, pharmaceutical companies, ethics committees, independent review boards, patient advocates and the regulatory authorities and promote an increase in the number and quality of HIT-IT clinical trials in the future. Particular emphasis was placed not only on the development of precise definitions to facilitate a better understanding between investigators but also on the importance of systematic serial biopsies as a driver for translational research and the need for the recording and reporting of data, to facilitate a better understanding of the key processes involved

Starting the Fight in the Tumor: Expert Recommendations for the Development of Human Intratumoral Immunotherapy (HIT-IT).

A European Society for Medical Oncology (ESMO)-sponsored expert meeting was held in Paris on 08 March 2018 which comprised 11 experts from academia, 11 experts from the pharmaceutical industry and two clinicians who were representatives of ESMO. The focus of the meeting was exclusively on the intratumoral injection/delivery of immunostimulatory agents with the aim of harmonizing the standard terms and methodologies used in the reporting of human intratumoral immunotherapy (HIT-IT) clinical trials to ensure quality assurance and avoid a blurring of the data reported from different studies. The goal was to provide a reference document, endorsed by the panel members, that could provide guidance to clinical investigators, pharmaceutical companies, ethics committees, independent review boards, patient advocates and the regulatory authorities, and promote an increase in the number and quality of HIT-IT clinical trials in the future. Particular emphasis was placed not only on the development of precise definitions to facilitate a better understanding between investigators, but also on the importance of systematic serial biopsies as a driver for translational research and the need for the recording and reporting of data, to facilitate a better understanding of the key processes involved

Starting the fight in the tumor: expert recommendations for the development of human intratumoral immunotherapy (HIT-IT)

A European Society for Medical Oncology (ESMO)-sponsored expert meeting was held in Paris on 8 March 2018 which comprised 11 experts from academia, 11 experts from the pharmaceutical industry and 2 clinicians who were representatives of ESMO. The focus of the meeting was exclusively on the intratumoral injection/delivery of immunostimulatory agents with the aim of harmonizing the standard terms and methodologies used in the reporting of human intratumoral immunotherapy (HIT-IT) clinical trials to ensure quality assurance and avoid a blurring of the data reported from different studies. The goal was to provide a reference document, endorsed by the panel members that could provide guidance to clinical investigators, pharmaceutical companies, ethics committees, independent review boards, patient advocates and the regulatory authorities and promote an increase in the number and quality of HIT-IT clinical trials in the future. Particular emphasis was placed not only on the development of precise definitions to facilitate a better understanding between investigators but also on the importance of systematic serial biopsies as a driver for translational research and the need for the recording and reporting of data, to facilitate a better understanding of the key processes involved