Object Detection Improves Tumour Segmentation in MR Images of Rare Brain Tumours

Tumour lesion segmentation is a key step to study and characterise cancer from MR neuroradiological images. Presently, numerous deep learning segmentation architectures have been shown to perform well on the specific tumour type they are trained on (e.g., glioblastoma in brain hemispheres). However, a high performing network heavily trained on a given tumour type may perform poorly on a rare tumour type for which no labelled cases allows training or transfer learning. Yet, because some visual similarities exist nevertheless between common and rare tumours, in the lesion and around it, one may split the problem into two steps: object detection and segmentation. For each step, trained networks on common lesions could be used on rare ones following a domain adaptation scheme without extra fine-tuning. This work proposes a resilient tumour lesion delineation strategy, based on the combination of established elementary networks that achieve detection and segmentation. Our strategy allowed us to achieve robust segmentation inference on a rare tumour located in an unseen tumour context region during training. As an example of a rare tumour, Diffuse Intrinsic Pontine Glioma (DIPG), we achieve an average dice score of 0.62 without further training or network architecture adaptation.

Association between oncology drug review times and public funding recommendations.

99 Background: New oncology drugs undergo detailed review of clinical, economic, and patient data. Thoroughly assessing these data can require lengthy review processes, in the absence of accelerated approval pathways. The aim of this study was to assess how cancer drug review times impact public funding recommendations. Methods: Drugs reviewed by Canada’s health technology assessment body, the pan-Canadian Oncology Drug Review (pCODR), from April 2012 to November 2020 were included in this study. Data was collected including Health Canada approval date, initial and final funding recommendations, treatment intent, drug class, clinical indication (tumour type) and incremental cost-effectiveness ratios (ICER). Univariable and multivariable analyses were used to determine the association between funding recommendations and review times. Results: Of the 227 applications submitted to pCODR, 168 had received positive funding recommendations. Amongst the total drug applications, 24 (14.3%) drugs were intended for the treatment of thoracic cancers, 19 (11.3%) for gastrointestinal cancers, 17 (10.1%) for genitourinary cancers, 17 (10.1%) for breast cancer, and 91 (54.2%) for other tumour sites. Median time from pCODR submission to final recommendation was longer for drugs indicated for the treatment of lung and breast cancer compared to those indicated for treatment of other tumours (223 vs. 212 vs. 203 days, respectively; Kruskal-Wallis p = 0.0322). Drugs with longer review times were more likely to receive a negative pCODR recommendation, even when adjusting for ICER (157 vs 298 days, Wilcoxon p-value = 0.0003). There was no association between positive or negative funding recommendation and tumour type. Conclusions: Oncology drugs with longer review times are less likely to receive recommendation for public funding in Canada. Addressing factors contributing to variance in review times and standardizing the review process can ensure equitable access to cancer drugs.

The Impact of COVID-19 Pandemic on Oncological Disease Extent at Staging FDG PET/CT: the ONCOVIPET Study.

Purpose: To investigate whether the COVID-19 pandemic and national lockdown had an impact on the extent of cancer disease at staging using FDG PET/CT as surrogate marker.Methods: Retrospective observational study including cancer patients submitted to FDG PET/CT for staging purposes from June 1 to October 31, 2020, and June 1 to October 31, 2021, respectively. Data regarding primary tumour, nodal (N) status and number of involved nodal stations, presence and number of distant metastases (M) were collected. Each scan was classified in limited vs advanced status. Data were aggregated across the study population and tumour type. Bi-weekly frequencies of the observed events were analysed. Results: 611 patients were included in the study (240 in 2019 vs. 371 in 2020, respectively). A significant increase in the rate of advanced disease patients in 2020 compared to 2019 was found (rate 1.56, p<0.001) as well as in the rate of N+ or M+ patients (rate 1.84 and 2.09 respectively, p<0.001) and in the rate of patients with a greater number of involved N stations or M (rate 2.01 and 2.06 respectively, p<0.001). Analysis by tumour type showed a significant increase of advanced disease, N+ or M+ status and number of involved N stations or M in lung cancer and lymphoma in 2020 compared with 2019 (p<0.003). Advanced disease rate resulted also significantly increased in gynaecologic cancer and N rate was significantly increased in gastro-intestinal cancer (p<0.05). Conclusion: The rate of cancer patients with advanced disease at staging FDG PET/CT increased by 1.5-fold in 2020, following the national lockdown due to the COVID-19 pandemic, compared to 2019 with a significant increase of patients with N involvement or M. Targeted health interventions are needed to mitigate the effects of the pandemic on patient outcome.

Specific cell differentiation in breast cancer: a basis for histological classification

Breast parenchyma progenitor cells show a high degree of phenotypic plasticity reflected in the wide range of morphology observed in benign and malignant breast tumours. Although there is evidence suggesting that all breast cancer (BC) arises from a common epithelial progenitor or stem cell located at the terminal duct lobular units (TDLUs), BC shows a broad spectrum of morphology with extensive variation in histological type and grade. This is related to the complexity of BC carcinogenesis including initial genetic changes in the cell of origin, subsequent genetic and epigenetic alterations and reprogramming that occur at various stages of BC development and the interplay with the surrounding microenvironment, factors which influence the process of differentiation. Differentiation in BC determines the morphology, which can be measured using histological grade and tumour type. Histological grade, which measures the similarity to the TDLUs, reflects the degree of differentiation whereas tumour type reflects the type of differentiation. Understanding BC phenotypic differentiation facilitates the accurate diagnosis and histological classification of BC with corresponding clinical implications in terms of disease behaviour, prognosis and management plans. In this review, we highlight the potential pathways that BC stem cells follow resulting in the development of different histological types of BC and how knowledge of these pathways impacts our ability to classify BC in diagnostic practice. We also discuss the role of cellular differentiation in producing metaplastic and neuroendocrine carcinomas of the breast and how the latter differ from their counterparts in other organs, with emphasis on clinical relevance.

Oncolytic Virotherapy Treatment of Breast Cancer: Barriers and Recent Advances

Oncolytic virotherapy (OV) is an emerging class of immunotherapeutic drugs. Their mechanism of action is two-fold: direct cell lysis and unmasking of the cancer through immunogenic cell death, which allows the immune system to recognize and eradicate tumours. Breast cancer is the most common cancer in women and is challenging to treat with immunotherapy modalities because it is classically an immunogenically “cold” tumour type. This provides an attractive niche for OV, given viruses have been shown to turn “cold” tumours “hot,” thereby opening a plethora of treatment opportunities. There has been a number of pre-clinical attempts to explore the use of OV in breast cancer; however, these have not led to any meaningful clinical trials. This review considers both the potential and the barriers to OV in breast cancer, namely, the limitations of monotherapy and the scope for combination therapy, improving viral delivery and challenges specific to the breast cancer population (e.g., tumour subtype, menopausal status, age).

Impact of the COVID-19 pandemic in treating gastrointestinal (GI) cancer patients receiving systemic anticancer treatment (SACT): The Guy's Cancer Centre experience.

3612 Background: The COVID-19 pandemic has hugely affected the spectrum of cancer care. Worldwide healthcare systems have rapidly reorganized cancer services to ensure patients continue to receive essential care whilst optimizing the use of systemic anti-cancer treatments (SACT) and minimizing exposure to SARS-CoV-2 infection. Our study aimed to identify the outcome of patients with gastrointestinal (GI) cancers in our Cancer Centre during the pandemic compared to the same period in 2019. Methods: Retrospective analysis of all GI patients receiving any SACT at Guy’s Cancer Centre from the 1 March-31 May 2020 and 2019. Demographic data (age, ethnicity, socio-economic status (SES), Performance status, cancer and SACT characteristics (type, intent and treatment-line) were collected during both periods. Also we collated the number of COVID-19 infections confirmed by PCR and severity defined by the WHO classification. Patients with clinical or radiological diagnosis were excluded. Results: 567 patients received SACT in 2019 and 417 patients in 2020 (26.4% less). No differences were observed in the demographic or tumour type characteristics. Commonest cancers in both periods were similar: colorectal (47.1, 47%), oesophago-gastric (29, 27.6%), pancreatic-biliary and NET tumours (23.8, 25.4%). However, there were a higher proportion of patients with advanced disease treated in 2020 (70.3% versus 55.2%). Treatment intent was similar in both years: radical (3.5 vs 3.8%), adjuvant (18.2% vs 17.3%), neoadjuvant (15.3% vs 12.7%) and palliative (63% vs 66.2%). There was an increase in the proportion of patients treated in the palliative first line setting (63.8% in 2020 vs 47.6% in 2019) and a reduction in the proportion of third or more treatment (8.7% versus 16.2%) mainly in the colorectal patients. Of 417 GI patients receiving SACT, 14 (3.35%) were diagnosed with COVID-19 infection. Of these, 64.3% were male, 92.9% were low SES and 35.7% were of Caucasian ethnicity. Colorectal cancer was the commonest (57.1%) tumour-type in the COVID-positive group and 57.1% had advanced disease. All the patients that died from COVID-19 were male. 13 patients were on chemotherapy and 1 was on targeted/biological treatment . None was in immunotherapy (n=4). Only one patient was neutropenic (grade 1). 8 patients (57.1%) had severe infection and there were 3 (21.4%) COVID-related deaths. Conclusions: Our study shows the delivery of SACT through the COVID-19 pandemic is relatively safe with low COVID-related mortality rate. It also reflects how we tailored the delivery of anti-cancer treatments to reduce the possible detrimental myelo-suppressive toxicities that could potentially put GI patients at higher risk of severe SARS-CoV-2 infection. This is crucial data that can inform anti-cancer treatment decision making during the protracted COVID-19 pandemic.

The Genomic Landscape of Lobular Breast Cancer

Invasive lobular carcinoma (ILC) is the second most common breast cancer histologic subtype, accounting for approximately 15% of all breast cancers. It is only recently that its unique biology has been assessed in high resolution. Here, we present a meta-analysis of ILC sequencing datasets, to provide a long-awaited ILC-specific resource, and to confirm the prognostic value and strength of association between a number of clinico-pathology features and genomics in this special tumour type. We consider panel (n = 684), whole exome (n = 215) and whole genome sequencing data (n = 48), and review histology of The Cancer Genome Atlas cases to assign grades and determine whether the ILC is of classic type or a variant, such as pleomorphic, prior to performing statistical analyses. We demonstrate evidence of considerable genomic heterogeneity underlying a broadly homogeneous tumour type (typically grade 2, estrogen receptor (ER)-positive); with genomes exhibiting few somatic mutations or structural alterations, genomes with a hypermutator phenotype, and tumours with highly rearranged genomes. We show that while CDH1 (E-cadherin) and PIK3CA mutations do not significantly impact survival, overall survival is significantly poorer for patients with a higher tumour mutation burden; this is also true for grade 3 tumours, and those carrying a somatic TP53 mutation (and these cases were more likely to be ER-negative). Taken together, we have compiled a meta-dataset of ILC with molecular profiling, and our analyses show that the genomic landscape significantly impacts the tumour’s variable natural history and overall survival of ILC patients.

Mixed adenoneuroendocrine tumour with squamous differentiation: a case report

Mixed adenoneuroendocrine carcinoma is a rare neoplasm with both epithelial and neuroendocrine components. To date, only a few cases of this neoplasm have been reported in the literature among which gastric mixed adenoneuroendocrine carcinoma is very rare. We are reporting a case of gastric mixed adenoneuroendocrine carcinoma with squamous cell differentiation. Histopathological features, biological behaviour and the treatment of this rare tumour type have been discussed briefly.

A retrospective analysis and literature review of neoplastic appendiceal mucinous lesions

Background At present, the term mucocele is outdated, and mucinous appendiceal neoplasm is preferred. Mucinous appendiceal neoplasm is an uncommon pathology that occurs predominantly in middle-aged women. Its classification and management have been the subject of debate in recent decades. The aim of this study was to analyse the incidence, clinical management and survival of these tumours diagnosed in our centre in the last 10 years. Methods This was a retrospective observational study of patients with a diagnosis of appendiceal neoplasms between 2009 and 2018 in our centre. Variables such as sex, age, tumour type, clinical status, diagnosis, treatment and survival were collected. All data were analysed using the statistical program IBM SPSS Statistic® version 25. Results Twenty-nine patients with a diagnosis of appendiceal neoplasm were identified, and 24 corresponded to neoplastic appendiceal mucinous lesions (85.7%). The average age was 59.7 ± 17.6 years. Most patients were women (15 cases; 62.5%). Most of them presented with chronic abdominal pain (37.5%), and the diagnosis was performed by computed tomography (CT) (50%). The treatment was surgical in all cases. The surgical technique depended on the findings and histology of the tumour. Conclusion Mucinous appendiceal neoplasms are an uncommon entity, and their pathological classification and management have recently changed.