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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).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.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.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.

Clinical characteristics of the breast cancer cohorts.

Subgroup analysis in IBE and IBD tumors. Kaplan-Meier plots comparing the probability of DMFS of patients classified as FID, WID and PID.

Detailed description of methods.

The abundance and functional orientation of tumor-infiltrating lymphocytes in breast cancer is associated with distant metastasis-free survival, yet how this association is influenced by tumor phenotypic heterogeneity is poorly understood. Here, a bioinformatics approach defined tumor biologic attributes that influence this association and delineated tumor subtypes that may differ in their ability to sustain durable antitumor immune responses. A large database of breast tumor expression profiles and associated clinical data was compiled, from which the ability of phenotypic markers to significantly influence the prognostic performance of a classification model that incorporates immune cell–specific gene signatures was ascertained. Markers of cell proliferation and intrinsic molecular subtype reproducibly distinguished two breast cancer subtypes that we refer to as immune benefit-enabled (IBE) and immune benefit-disabled (IBD). The IBE tumors, comprised mostly of highly proliferative tumors of the basal-like, HER2-enriched, and luminal B subtypes, could be stratified by the immune classifier into significantly different prognostic groups, while IBD tumors could not, indicating the potential for productive engagement of metastasis-protective immunity in IBE tumors, but not in IBD tumors. The prognostic stratification in IBE was independent of conventional variables. Gene network analysis predicted the activation of TNFα/IFNγ signaling pathways in IBE tumors and the activation of the transforming growth factor-β pathway in IBD tumors. This prediction supports a model in which breast tumors can be distinguished on the basis of their potential for metastasis-protective immune responsiveness. Whether IBE and IBD represent clinically relevant contexts for evaluating sensitivity to immunotherapeutic agents warrants further investigation. Cancer Immunol Res; 4(7); 600–10. ©2016 AACR.

Supplementary Table S1: Summary of the TCGA tumour sets for which RNAseq V2 RSEM normalised data was downloaded on 20th October 2015 and used for TP53 transcript expression analyses. Supplementary Table S2: Summary of QC for RNAseq and RNA expression using RNAseq for the nine human cell lines. Supplementary Table S3: UCSC and Locus Reference Genomic (LRG) IDs for canonical TP53 transcript variants. Supplementary Table S4: Primer sequences used for ddPCR and RT-qPCR. Supplementary Table S5: Read data for RNAseq RSEM Expected count, RNAseq Tuxedo-FPKM, RNAseq RSEM-FPKM, ddPCR and RT-qPCR. Supplementary Table S6: RNAseq reads containing both PCR primers Supplementary Table S7: RNAseq reads in 125nt specific regions in exon 4 and AluJB upstream and exon5/6 downstream of the 125nt unique to the 5'-UTR of delta133TP53 transcript subclass Supplementary Table S8: Mutations and sequencing errors do not significantly affect alignment of sequence reads to the TP53 locus Supplementary Figure S1: Shows examples of fluorescence amplitude by ddPCR Supplementary Figure S2: Dissociation curves for TP53 primer pairs by RT-qPCR Supplementary Figure S3: Sanger Sequencing of the amplicons for FL/delta40TP53_T1, FL/delta40TP53_T2, delta133TP53, TP53alpha and TP53beta Supplementary Figure S4: Relative abundance of TP53 transcript subclasses relative to FL/delta40TP53_T1.

TP53 undergoes multiple RNA-splicing events, resulting in at least nine mRNA transcripts encoding at least 12 functionally different protein isoforms. Antibodies specific to p53 protein isoforms have proven difficult to develop, thus researchers must rely on the transcript information to infer isoform abundance. In this study, we used deep RNA-seq, droplet digital PCR (ddPCR), and real-time quantitative reverse transcriptase PCR (RT-qPCR) from nine human cell lines and RNA-seq data available for tumors in The Cancer Genome Atlas to analyze TP53 splice variant expression. All three methods detected expression of the FL/40TP53α_T1 variant in most human tumors and cell lines. However, other less abundant variants were only detected with PCR-based methods. Using RNA-seq simulation analysis, we determined why RNA-seq is unable to detect less abundant TP53 transcripts and discuss the implications of these findings for the general interpretation of RNA-seq data. Cancer Res; 76(24); 7151–9. ©2016 AACR.

Genomic analysis of tumors is transforming our understanding of cancer. However, although a great deal of attention is paid to the accuracy of the cancer genomic data itself, less attention has been paid to the accuracy of the associated clinical information that renders the genomic data useful for research. In this brief communication, we suggest that omissions and errors in clinical annotations have a major impact on the interpretation of cancer genomic data. We describe our discovery of annotation omissions and errors when reviewing an already carefully annotated colorectal cancer gene expression dataset from our laboratory. The potential importance of clinical annotation omissions and errors was then explored using simulation analyses with an independent genomic dataset. We suggest that the completeness and veracity of clinical annotations accompanying cancer genomic data require renewed focus by the oncology research community, when planning new collections and when interpreting existing cancer genomic data.

Circulating tumour DNA (ctDNA) analysis promises to improve the care of people with cancer, address health inequities and guide translational research. This observational cohort study used ctDNA to follow 29 New Zealand (NZ) unresectable advanced-stage cutaneous melanoma patients through multiple cycles of immunotherapy, to identify the breadth and complexity of tumour genomic information that ctDNA analysis can reliably report. During the course of treatment, a high level of dynamic mutational complexity was identified in blood plasma of these patients, including: multiple BRAF mutations in the same patient, clinically-relevant BRAF mutations emerging through therapy, and co-occurring sub-clonal BRAF and NRAS mutations. The technical validity of this ctDNA analysis was supported by high sample analysis-reanalysis concordance as well as by concordance between three ctDNA measurement technologies: droplet digital polymerase chain reaction (ddPCR), a custom melanoma-specific amplicon next-generation sequencing (NGS) panel and mass spectrometry. In addition, we observed >90% concordance in the detection of ctDNA when using cell-stabilising collection tubes followed by 7-day delayed processing, compared to standard EDTA blood collection protocols with rapid processing. We also found that undetectability of ctDNA at a proportion of treatment cycles was associated with both clinical benefit (best RECIST response) and prognosis (disease-specific survival). In summary, we found that multiple ctDNA processing and analysis methods consistently identified complex longitudinal patterns of clinically-relevant mutations, adding support for expanded implementation of this technology to guide in-treatment tailored cancer therapy.

Increases in cancer survival may increase cancer prevalence and demand for healthcare. We aimed to estimate cancer prevalence in the New Zealand population.We used national linked health, social and census datasets from the Stats NZ Integrated Data Infrastructure to identify the number of New Zealand residents who had at least one cancer diagnosis in New Zealand. We included all primary cancers recorded on the New Zealand Cancer Registry from January 1995 to June 2013, and used the 2013 census for demographic and socioeconomic data.On 30 June 2013, 140,600 of 4,438,900 (3.2%) New Zealand residents had been diagnosed with cancer in the last 18.5 years. In ≥15 year olds, the age-standardised prevalence of cancer diagnosed 0 to ≤1 year, and1 to ≤5 years, prior to 30 June 2013 was 0.4% and 1.1% in men and 0.3% and 0.9% in women, respectively. Over the 18.5-year period prevalence was greatest in the oldest ages, European/Other, highest qualified, highest income, least deprived, ex-smokers, and Canterbury, Bay of Plenty and Nelson/Marlborough District Health Boards (age-standardised).Groups with the highest survival and the greatest access to healthcare had the highest cancer prevalences.

New Zealand has one of the highest incidences of rectal cancer in the world, and its optimal management requires a multidisciplinary approach. A National Rectal Cancer Summit was convened in August 2013 to discuss management of rectal cancer in the New Zealand context, to highlight controversies and discuss domestic priorities for the future. This paper summarises the priorities for treatment, research and policy for rectal cancer services in New Zealand identified as part of the Summit in August. The following priorities were identified: - Access to high-quality information for service planning, review of outcomes, identification of inequities and gaps in provision, and quality improvement; - Engagement with the entire sector, including private providers; - Focus on equity; - Emerging technologies; - Harmonisation of best practice; - Importance of multidisciplinary team meetings. In conclusion, improvements in outcomes for patients with rectal cancer in New Zealand will require significant engagement between policy makers, providers, researchers, and patients in order to ensure equitable access to high quality treatment, and strategic incorporation of emerging technologies into clinical practice. A robust clinical information framework is required in order to facilitate monitoring of quality improvements and to ensure that equitable care is delivered.