ECCO essential requirements for quality cancer care : Oesophageal and gastric cancer

Background: ECCO essential requirements for quality cancer care (ERQCC) are checklists and explanations of organisation and actions that are necessary to give high-quality care to patients who have a specific type of cancer. They are written by European experts representing all disciplines involved in cancer care. ERQCC papers give oncology teams, patients, policymakers and managers an overview of the elements needed in any healthcare system to provide high quality of care throughout the patient journey. References are made to clinical guidelines and other resources where appropriate, and the focus is on care in Europe. Oesophageal and gastric: essential requirements for quality care: Oesophageal and gastric (OG) cancers are a challenging tumour group with a poor prognosis and wide variation in outcomes among European countries. Increasing numbers of older people are contracting the diseases, and treatments and care pathways are becoming more complex in both curative and palliative settings. High-quality care can only be a carried out in specialised OG cancer units or centres which have both a core multidisciplinary team and an extended team of allied professionals, and which are subject to quality and audit procedures. Such units or centres are far from universal in all European countries. It is essential that, to meet European aspirations for comprehensive cancer control, healthcare organisations implement the essential requirements in this paper, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship. Conclusion: Taken together, the information presented in this paper provides a comprehensive description of the essential requirements for establishing a high-quality OG cancer service. The ERQCC expert group is aware that it is not possible to propose a one size fits all' system for all countries, but urges that access to multidisciplinary units or centres must be guaranteed for all those with OG cancer.Peer reviewe

The requirements of a specialist breast centre

Abstract This article is an update of the requirements of a specialist breast centre, produced by EUSOMA and endorsed by ECCO as part of Essential Requirements for Quality Cancer Care (ERQCC) programme, and ESMO. To meet aspirations for comprehensive cancer control, healthcare organisations must consider the requirements in this article, paying particular attention to multidisciplinarity and patient-centred pathways from diagnosis, to treatment, to survivorship.Peer reviewe

Polychronous (Early Cretaceous to Palaeogene) emplacement of the Mundwara alkaline complex, Rajasthan, India: 40Ar/39Ar geochronology, petrochemistry and geodynamics

The Mundwara alkaline plutonic complex (Rajasthan, north-western India) is considered a part of the Late Cretaceous–Palaeogene Deccan Traps flood basalt province, based on geochronological data (mainly 40Ar/39Ar, on whole rocks, biotite and hornblende). We have studied the petrology and mineral chemistry of some Mundwara mafic rocks containing mica and amphibole. Geothermobarometry indicates emplacement of the complex at middle to upper crustal levels. We have obtained new 40Ar/39Ar ages of 80–84 Ma on biotite separates from mafic rocks and 102–110 Ma on whole-rock nepheline syenites. There is no evidence for excess 40Ar. The combined results show that some of the constituent intrusions of the Mundwara complex are of Deccan age, but others are older and unrelated to the Deccan Traps. The Mundwara alkaline complex is thus polychronous and similar to many alkaline complexes around the world that show recurrent magmatism, sometimes over hundreds of millions of years. The primary biotite and amphibole in Mundwara mafic rocks indicate hydrous parental magmas, derived from hydrated mantle peridotite at relatively low temperatures, thus ruling out a mantle plume. This hydration and metasomatism of the Rajasthan lithospheric mantle may have occurred during Jurassic subduction under Gondwanaland, or Precambrian subduction events. Low-degree decompression melting of this old, enriched lithospheric mantle, due to periodic diffuse lithospheric extension, gradually built the Mundwara complex from the Early Cretaceous to Palaeogene time

1534 Clinical activity of SD-101 with immune checkpoint inhibition (ICI) in metastatic uveal melanoma liver metastasis (MUM-LM) from the PERIO-01 Phase 1 trial

BackgroundMUM-LM are resistant to ICIs for several reasons including the prevalence of myeloid-derived suppressor cells (MDSCs). PFS has been limited, even with approved therapies such as tebentafusp (median 3.3 months) with grade 3/4 AE rates typically >30%. TLR9 agonists are capable of MDSC polarization but drug delivery has historically been limited using an intra-tumoral approach. Pressure-enabled drug delivery (PEDDTM) of SD-101, a TLR9 agonist, has the potential to overcome these barriers to improve outcomes.MethodsPERIO-01 is a phase 1 trial of hepatic arterial SD-101 via PEDD in MUM-LM (NCT04935229), with dose-escalation cohorts as monotherapy (Cohort A), with nivolumab (Cohort B), or nivolumab + ipilimumab (Cohort C). SD-101 is delivered over 2 outpatient cycles, with 3 weekly doses/cycle.Results53 patients received at least one dose of SD-101: 13 in Cohort A, 25 in Cohort B, and 15 in Cohort C. Median age was 65 and 45% were female. 70% received prior MUM-LM treatment, and 8 (15%) received tebentafusp. Fifteen participants (28%) had LM >5cm and 18 (44%) had >10 LMs. One patient experienced partial response (Cohort B 4 mg) that is ongoing at 258 days. Six additional patients had decreases in target lesion size (SD), 3 ongoing at a median follow-up of 168 days. Across dose levels, median PFS was highest in Cohort B (2 mg) at 11.7 months, and disease control rate of 86% (6/7 SD). Serious grade 3/4 treatment-related AEs (TRAEs) to SD-101 or ICI were documented in 8% of subjects: 0% in Cohort A, 4% in Cohort B, and 20% in Cohort C, with an overall Grade 3/4 TRAE rate of 21%. PEDD of SD-101 resulted in reductions in LM monocytic MDSC (mMDSC) by immunofluorescence, along with decreased expression of ARG1, CD163, and FASN. We also observed evidence of immune activation in LM with increased CD4+ and CD8+ T cells, decreased Treg, and increased IFNg and IFNa2 gene expression. These were associated with evidence of systemic immune activation peripherally characterized by increased proliferating CD8+ T and NK cells, and increased IP-10, TNFa, IFNg, IL-2R, and IL-18. Among 25 patients with evaluable ctDNA data, 68% had a decrease relative to peak, with complete clearance in 28%.ConclusionsDelivery of SD-101 by PEDD plus systemic ICI in MUM-LM patients results in clinical activity with median PFS of 11.7 months, MDSC re-programming, and evidence of peripheral and intra-tumoral immune activation. Phase 2 of PERIO-01 is planned for expansion of the optimal dose.Trial RegistrationNCT04935229Ethics ApprovalThe study was IRB approved at all sites and participants signed written informed consen