Quality Performance Indicators for the Surgical Management of Oesophageal Cancer: A Systematic Literature Review.

BACKGROUND: The objective of this systematic review was to identify pre-existing quality performance indicators (QPIs) for the surgical management of oesophageal cancer (OC). These QPIs can be used to objectively measure and compare the performance of individual units and capture key elements of patient care to improve patient outcomes. METHODS: A systematic literature search of PubMed, MEDLINE, Scopus and Embase was conducted. Articles reporting on the quality of healthcare in relation to oesophageal neoplasm or cancer and the surgical treatment of OC available until the 1st of March 2022 were included. RESULTS: The final list of articles included retrospective reviews (n = 13), prospective reviews (n = 8), expert guidelines (n = 1) and consensus (n = 1). The final list of QPIs was categorized as process, outcome or structural measures. Process measures included multidisciplinary involvement, availability of multimodality diagnostic and treatment pathways and surgical metrics. Outcome measures included reoperation and readmission rates, the achievement of RO resection and length of hospital stay. Structural measures include multidisciplinary meetings. CONCLUSIONS: This systematic review summarizes QPIs for the surgical treatment of OC. The data will serve as an introduction to establishing a quality initiative project for OC resections.

A core set of quality performance indicators for HPB procedures: a global consensus for hepatectomy, pancreatectomy, and complex biliary surgery.

BACKGROUND: Surgery for hepatopancreaticobiliary (HPB) conditions is performed worldwide. This investigation aimed to develop a set of globally accepted procedural quality performance indicators (QPI) for HPB surgical procedures. METHODS: A systematic literature review generated a dataset of published QPI for hepatectomy, pancreatectomy, complex biliary surgery and cholecystectomy. Using a modified Delphi process, three rounds were conducted with working groups composed of self-nominating members of the International Hepatopancreaticobiliary Association (IHPBA). The final set of QPI was circulated to the full membership of the IHPBA for review. RESULTS: Seven "core" indicators were agreed for hepatectomy, pancreatectomy, and complex biliary surgery (availability of specific services on site, a specialised surgical team with at least two certified HPB surgeons, a satisfactory institutional case volume, synoptic pathology reporting, undertaking of unplanned reintervention procedures within 90 days, the incidence of post-procedure bile leak and Clavien-Dindo grade ≥III complications and 90-day post-procedural mortality). Three further procedure specific QPI were proposed for pancreatectomy, six for hepatectomy and complex biliary surgery. Nine procedure-specific QPIs were proposed for cholecystectomy. The final set of proposed indicators were reviewed and approved by 102 IHPBA members from 34 countries. CONCLUSIONS: This work presents a core set of internationally agreed QPI for HPB surgery.

Quality performance indicators for hepato-pancreatico-biliary procedures: a systematic review.

BACKGROUND: This systematic review was undertaken to define and summarize existing, proposed quality performance indicators (QPI) for hepato-pancreatico-biliary (HPB) procedures. METHODS: A systematic literature review identified studies reporting on quality indicators for cholecystectomy, hepatectomy, pancreatectomy and complex biliary surgical procedures. The databases searched were MEDLINE, EMBASE, PubMed, and SCOPUS, with all literature available until the search date of 1 May 2020 included. The reference lists of all included papers, as well as related review articles, were manually searched to identify further relevant studies. RESULTS: Forty-five publications report quality indicators for pancreatectomy (n = 22), hepatectomy (n = 7), HPB resections in general (n = 12), and cholecystectomy (n = 6). No publications proposed QPI for complex biliary surgery. The 45 papers used national audit (n = 18), consensus methodology (n = 5), state-wide audit (n = 3), unit audit (n = 9), review methodology (n = 9), and survey methodology (n = 1). Sixty-one QPI were reported for pancreatectomy, 22 reported for hepatectomy, and 14 reported for HPB resections in general, in domains of infrastructure, provider, and documentation. Fourteen infrastructure and provider-based QPI were reported for cholecystectomy. CONCLUSIONS: There are few internationally agreed QPI for HPB procedures that allow global comparison of provider performance and that set aspirational goals for patient care and experience.

Palliative radiotherapy is effective for both well- and poorly differentiated neuroendocrine neoplasms.

INTRODUCTION: The outcomes of palliative radiation therapy (RT) for neuroendocrine neoplasms (NEN) are seldom reported. We investigated outcomes following palliative radiotherapy in a cohort of patients with NENs. We hypothesised that well-differentiated NEN will be less likely to have a clinical response than poorly differentiated NEN. METHODS: Patients who received at least one course of palliative RT were identified using the New Zealand NETwork! Registry. Patients with Merkel cell carcinoma, pulmonary small cell carcinoma or asymptomatic patients were excluded. Clinical response to RT within 90 days and overall survival were analysed alongside clinical variables (fractionation, RT site, tumour differentiation and tumour primary site). RESULTS: The cohort comprised 79 patients, with 147 courses of palliative RT delivered. Clinical response was measurable for 100 courses, with clinical response rate of 76%. A course delivered to a well-differentiated NEN was associated with 2.02-fold (95% CI 0.67, 6.12; P = 0.21) increase in odds of a clinical response compared to a poorly differentiated NEN. Median overall survival from the first fraction of RT was 94 days (95% CI 80, 138 days). Overall survival was higher in well-differentiated NEN than in poorly differentiated NEN (HR 0.2, 95% CI 0.10-0.40, P-value < 0.001); 30-day mortality was 7%. There were significantly reduced odds of clinical response for non-bone sites, and for courses >10 fractions compared to a single fraction. CONCLUSION: Palliative RT is an appropriate option for management of symptoms in patients with both well- and poorly differentiated metastatic NEN.

Quality performance indicators for oesophageal and gastric cancer: ANZ expert Delphi consensus.

BACKGROUND: Quality performance indicators for the management of oesophagogastric cancer can be used to objectively measure and compare the performance of individual units and capture key elements of patient care to improve patient outcomes. METHODS: Two systematic reviews were completed to identify evidence-based quality performance indicators for the surgical management of oesophagogastric cancer. Based on the indicators identified, a two-round modified Delphi process with invitations was sent to all members of the Australia and Aotearoa New Zealand Gastric and Oesophageal Surgery Association. The expert working group discussed each suggested indicator and either removed, added, or adjusted the list of indicators of oesophagogastric cancer. RESULTS: The final list of both OG cancer indicators included Specialized Multi-disciplinary team discussion, Endoscopy documentation, Staging Contrast CT Chest/Abdomen and Pelvis, Neoadjuvant or Adjuvant chemo/radiotherapy administered in accordance with the Local multi-disciplinary team, Pathological margin clearance (R0 Resection), Lymphadenectomy retrieving 15 or more nodes, Formal review of pathological findings and documentation, Postoperative complications, 30-day and 90-day postoperative mortality, clinical surveillance and Specialized Dietetic guidance. Indicators specific to gastric cancer included Preoperative biopsy for pathological diagnosis and Staging Laparoscopy. Indicators specific to oesophageal cancer include positron emission tomography scan if CT negative for metastasis, Perioperative Oesophagectomy Care Pathway, length of stay of 21 days or more, and Unplanned readmission within 30 days. CONCLUSIONS: The results of this study present a core set of indicators for the surgical management of oesophagogastric cancer that can be used to measure quality and compare performance between different units.

Chromosomal Aberrations Accumulate during Metastasis of Virus-Negative Merkel Cell Carcinoma.

Merkel cell carcinoma is a rare, aggressive skin tumor initiated by polyomavirus integration or UV light DNA damage. In New Zealand, there is a propensity toward the UV-driven form (31 of 107, 29% virus positive). Using archival formalin-fixed, paraffin-embedded tissues, we report targeted DNA sequencing covering 246 cancer genes on 71 tumor tissues and 38 nonmalignant tissues from 37 individuals, with 33 of 37 being negative for the virus. Somatic variants of New Zealand virus-negative Merkel cell carcinomas partially overlapped with those reported overseas, including TP53 variants in all tumors and RB1, LRP1B, NOTCH1, and EPHA3/7 variants each found in over half of the cohort. Variants in genes not analyzed or reported in previous studies were also found. Cataloging variants in TP53 and RB1 from published datasets revealed a broad distribution across these genes. Chr 1p gain and Chr 3p loss were identified in around 50% of New Zealand virus-negative Merkel cell carcinomas, and RB1 loss of heterozygosity was found in 90% of cases. Copy number variants accumulate in most metastases. Virus-negative Merkel cell carcinomas have complex combinations of somatic DNA-sequence variants and copy number variants. They likely carry the small genomic changes permissive for metastasis from early tumor development; however, chromosomal alterations may contribute to driving metastatic progression.

Complex Patterns of Genomic Heterogeneity Identified in 42 Tumor Samples and ctDNA of a Pulmonary Atypical Carcinoid Patient.

Tumor evolution underlies many challenges facing precision oncology, and improving our understanding has the potential to improve clinical care. This study represents a rare opportunity to study tumor heterogeneity and evolution in a patient with an understudied cancer type. A patient with pulmonary atypical carcinoid, a neuroendocrine tumor, metastatic to 90 sites, requested and consented to donate tissues for research. 42 tumor samples collected at rapid autopsy from 14 anatomically distinct sites were analyzed through DNA whole-exome sequencing and RNA sequencing, and five analyzed through linked-read sequencing. Targeted DNA sequencing was completed on two clinical tissue biopsies and one blood plasma sample. Chromosomal alterations and gene variants accumulated over time, and specific chromosomal alterations preceded the single predicted gene driver variant (ARID1A). At the time of autopsy, all sites shared the gain of one copy of Chr 5, loss of one copy of Chr 6 and 21, chromothripsis of one copy of Chr 11, and 39 small variants. Two tumor clones (carrying additional variants) were detected at metastatic sites, and occasionally in different regions of the same organ (e.g., within the pancreas). Circulating tumor DNA (ctDNA) sequencing detected shared tumor variants in the blood plasma and captured marked genomic heterogeneity, including all metastatic clones but few private tumor variants. This study describes genomic tumor evolution and dissemination of a pulmonary atypical carcinoid donated by a single generous patient. It highlights the critical role of chromosomal alterations in tumor initiation and explores the potential of ctDNA analysis to represent genomically heterogeneous disease. Significance: DNA sequencing data from tumor samples and blood plasma from a single patient highlighted the critical early role of chromosomal alterations in atypical carcinoid tumor development. Common tumor variants were readily detected in the blood plasma, unlike emerging tumor variants, which has implications for using ctDNA to capture cancer evolution.

Quality performance indicators for the surgical treatment of gastric adenocarcinoma: a systematic review.

BACKGROUND: A systematic review was undertaken to identify existing quality performance indicators (QPI) for the surgical treatment of gastric adenocarcinoma (GA) with the aim of defining a set of QPIs that can be used to assist in the accreditation of institutions for training, allow cross jurisdiction comparison of treatment and outcomes, as well as provide a basis to develop quality improvement programs. These QPI's capture key components of patient care that are fundamental to overall outcome. METHODS: A systematic literature review was conducted searching MEDLINE, PubMed, EMBASE, and SCOPUS with all literature available until the date of 1 August 2021 included. Search terms utilized were 'Quality of health care OR Quality improvement or Quality control OR Quality indicators', AND 'Gastrectomy' OR 'Stomach neoplasm' OR 'Adenocarcinoma' OR 'Gastric resection' OR 'Gastric cancer'. RESULTS: Twelve articles were included in the final analysis. The selected studies included editorials (n = 2), retrospective review of institutional experience (n = 5), cohort studies (n = 2), survey methodology (n = 1), expert guidelines (n = 1) and consensus statement (n = 1). For GC QPIs, process measures included patient discussion at multi-disciplinary meetings, access to perioperative multimodal diagnostic pathways, and specific surgical metrics (margin negative resections and adequate lymphadenectomy). Outcome measures included the RO resection rate, reoperation, readmission rate, and length of hospital stay. CONCLUSIONS: There is a relative paucity of internationally agreed QPI for the surgical management of gastric adenocarcinoma. The data from this review will form the basis of a project to develop internationally agreed and feasible QPI for gastric cancer resections.

Survival of patients with small bowel neuroendocrine neoplasms in Auckland, Aotearoa New Zealand.

BACKGROUND: Small intestinal Neuroendocrine Neoplasms (SI-NENs) are the most common primary malignancy of the small bowel. The aim of this study is to define the survival of patients with an SI-NEN in Auckland, Aotearoa New Zealand (AoNZ). METHODS: A retrospective study of all patients diagnosed with a jejunal or ileal SI-NEN in the Auckland region between 2000 and 2012 was performed. The New Zealand NETwork! Registry was searched to identify the study cohort. Retrospective data collection was performed to collect stage, survival and follow up data. RESULTS: One hundred and seven patients were included in the study. The mean age of patients was 62.8 years (SD 11.9). The 5 and 10-year disease-specific survival for all patients was 66.1% (95% CI 56.5-75.7%) and 61.8% (95% CI 51.8-71.8%), respectively. Ten-year disease-specific survival was 100% for stage I and II, 74% (95%CI 61.7-84.4%) for stage III and 33.9% (95%CI 16.9-35.6%) for stage IV SI-NEN. Eleven of 40 (27.5%) patients with stage III disease had recurrence and 3 of 7 (42.8%) patients with stage IV disease had recurrence. In patients with stage IV disease, neither primary resection (HR 2.25, 95% CI 0.92-5.5) nor distant resection (HR 1.72, 95% CI 0.63-4.7) were significantly associated with a disease-specific or overall survival benefit. CONCLUSION: This study demonstrates that stage at SI-NEN diagnosis is associated with survival, but resection of the primary or distant metastases in patients with stage IV disease is not. There was no recurrence in patients with stage I or II disease after complete resection.

Consensus-Derived Quality Performance Indicators for Neuroendocrine Tumour Care.

Quality performance indicators (QPIs) are used to monitor the delivery of cancer care. Neuroendocrine tumours (NETs) are a family of individually uncommon cancers that derive from neuroendocrine cells or their precursors, and can occur in most organs. There are currently no QPIs available for NETs and their heterogeneity makes QPI development difficult. CommNETs is a collaboration between NET clinicians, researchers and advocates in Canada, Australia and New Zealand. We created QPIs for NETs using a three-step consensus process. First, a multidisciplinary team used the nominal group technique to create candidates (n = 133) which were then curated into appropriateness statements (62 statements, 44 sub-statements). A two-stage modified RAND/UCLA Delphi consensus process was conducted: an online survey rated the statement appropriateness then the top-ranked statements (n = 20) were assessed in a face-to-face meeting. Finally, 10 QPIs met consensus criteria; documentation of primary site, proliferative index, differentiation, tumour board review, use of a structured pathology report, presence of distant metastasis, 5- and 10-year disease-free and overall survival. These NET QPIs will be trialed as a method to monitor and improve care for people with NETs and to facilitate international comparison.

Recurrent loss of heterozygosity correlates with clinical outcome in pancreatic neuroendocrine cancer.

Pancreatic neuroendocrine tumors (pNETs) are uncommon cancers arising from pancreatic islet cells. Here we report the analysis of gene mutation, copy number, and RNA expression of 57 sporadic well-differentiated pNETs. pNET genomes are dominated by aneuploidy, leading to concordant changes in RNA expression at the level of whole chromosomes and chromosome segments. We observed two distinct patterns of somatic pNET aneuploidy that are associated with tumor pathology and patient prognosis. Approximately 26% of the patients in this series had pNETs with genomes characterized by recurrent loss of heterozygosity (LoH) of 10 specific chromosomes, accompanied by bi-allelic MEN1 inactivation and generally poor clinical outcome. Another ~40% of patients had pNETs that lacked this recurrent LoH pattern but had chromosome 11 LoH, bi-allelic MEN1 inactivation, and universally good clinical outcome. The somatic aneuploidy allowed pathogenic germline variants (e.g., ATM) to be expressed unopposed, with RNA expression patterns showing inactivation of downstream tumor suppressor pathways. No prognostic associations were found with tumor morphology, single gene mutation, or expression of RNAs reflecting the activity of immune, differentiation, proliferative or tumor suppressor pathways. In pNETs, single gene mutations appear to be less important than aneuploidy, with MEN1 the only statistically significant recurrently mutated driver gene. In addition, only one pNET in the series had clearly actionable single nucleotide variants (SNVs) (in PTEN and FLCN) confirmed by corroborating RNA expression changes. The two clinically relevant patterns of LoH described here define a novel oncogenic mechanism and a plausible route to genomic precision oncology for this tumor type.