Development of a multi-gene PCR assay for the prediction of the response to hormone therapy in breast cancer

Deux tiers des cancers du sein expriment des récepteurs hormonaux ostrogéniques (tumeur ER-positive) et la croissance de ces tumeurs est stimulée par l’estrogène. Des traitements adjuvant avec des anti-estrogènes, tel que le Tamoxifen et les Inhibiteurs de l’Aromatase peuvent améliorer la survie des patientes atteinte de cancer du sein. Toutefois la thérapie hormonale n’est pas efficace dans toutes les tumeurs mammaires ER-positives. Les tumeurs peuvent présenter avec une résistance intrinsèque ou acquise au Tamoxifen. Présentement, c’est impossible de prédire quelle patiente va bénéficier ou non du Tamoxifen. Des études préliminaires du laboratoire de Dr. Mader, ont identifié le niveau d’expression de 20 gènes, qui peuvent prédire la réponse thérapeutique au Tamoxifen (survie sans récidive). Ces marqueurs, identifié en utilisant une analyse bioinformatique de bases de données publiques de profils d’expression des gènes, sont capables de discriminer quelles patientes vont mieux répondre au Tamoxifen. Le but principal de cette étude est de développer un outil de PCR qui peut évaluer le niveau d’expression de ces 20 gènes prédictif et de tester cette signature de 20 gènes dans une étude rétrospective, en utilisant des tumeurs de cancer du sein en bloc de paraffine, de patients avec une histoire médicale connue. Cet outil aurait donc un impact direct dans la pratique clinique. Des traitements futiles pourraient être éviter et l’indentification de tumeurs ER+ avec peu de chance de répondre à un traitement anti-estrogène amélioré. En conséquence, de la recherche plus appropriée pour les tumeurs résistantes au Tamoxifen, pourront se faire.Two thirds of breast cancers express the estrogen receptor (ER-positive tumours) and estrogens stimulate growth of these tumours. Adjuvant therapy with anti-estrogens such as Tamoxifen and Aromatase Inhibitors has been shown to increase survival in breast cancer patients. This treatment is, however, not successful in all ER-positive tumours. Tumours can present intrinsic or acquired resistance to Tamoxifen. However, it is currently impossible to predict which patient will benefit from Tamoxifen therapy and which will not. Preliminary studies in Dr. Mader’s lab have identified 20 genes whose expression levels in tumours are able to predict the response to Tamoxifen therapy (disease-free survival). These markers, identified using bioinformatics analysis of published gene expression datasets, were able to discriminate patients that would respond best to Tamoxifen from those that did not. The overall purpose of this study is to develop a PCR kit to monitor expression levels of these 20 genes and to test this 20-gene signature in a retrospective study using paraffin-embedded breast cancer tissues of patients with a known medical history. This tool may thus have a direct impact on clinical practice through the development of markers of therapeutic success for treatment with Tamoxifen and possibly Aromatase Inhibitors. Futile treatments would be avoided thus preventing needless side effects, and improved identification of ER+ tumours with a low chance of success to anti-estrogen therapy. This will facilitate research into more appropriate treatments for hormone resistant tumours

Surveillance Post Surgery for Retroperitoneal Soft Tissue Sarcoma

Complete en bloc surgical resection offers the best opportunity for the cure of primary retroperitoneal sarcomas (RPS). The potential for disease recurrence, in the form of both loco-regional recurrence and distant metastases, underpins the rationale for postoperative surveillance. There is a paucity of high-quality evidence underpinning follow-up for RPS patients, and most practice guidelines draw from expert opinion and evidence from soft tissue sarcomas of the extremities. The available observational retrospective data analysis has failed to demonstrate that high-intensity radiological surveillance improves the overall survival in patients. The lack of a robust evidence base has given rise to variations in approaches to post-operative surveillance strategies adopted by specialist centres managing RPS across the world. More high-quality prospective research is needed and planned to more clearly support surveillance approaches that balance oncologic outcomes, patient-centric care, and health service value. Risk stratification tools exist and are available for use in routine practice. Their use will likely support more individualised post-operative surveillance moving forward. Surveillance will likely be underpinned by serial radiological imaging for the medium term. However, developments in genomics offer hope for biomarkers such as ctDNA to impact patient care positively in the future and further support individualised patient care pathways

Ensuring a Safe and Qualitative Diagnostic Biopsy for Retroperitoneal Sarcomas

Retroperitoneal sarcomas represent one third of neoplasms in the retroperitoneum and as such are an important entity when evaluating masses in this area. They are often identified incidentally as they present with non-specific symptoms and are only detectable on physical exam when they have grown to a large size. This group of tumours is a challenge for physicians as it encompasses over 50 different histological subtypes and the course of treatment greatly depends on histopathological diagnosis. Biopsy of these lesions has recently become standard of care when evaluating a suspected retroperitoneal sarcoma. However, historically, there has been specula- tion over whether this practice promotes needle tract seeding resulting in local recurrence which has resulted in limited research on the topic. As such, there is a lack of literature describing the best parameters for a safe and effective biopsy of these lesions. Our ongoing research aims to identify biopsy parameters which yield a safe and qualitative diagnostic biopsy while minimizing complications and local recurrence with the goal of consistent and quality care for all patients presenting with retroperitoneal lesions. RÉSUMÉ Les sarcomes rétropéritonéaux constituent un tiers des néoplasmes du rétropéritoine, et représentent ainsi une entité importante lors de l’évaluation de masses dans cet espace. Ils sont souvent découverts fortuitement puisqu’ils se manifestent par des symptômes non spécifiques et sont seulement décelables à l’examen physique lorsqu’ils atteignent une taille considérable. Ce groupe de tumeurs représente un défi pour les médecins, car il comprend plus de 50 différents sous-types histologiques et le traitement dépend largement du diagnostic histopathologique. La biopsie de ces lésions est récemment devenue la norme en matière de soins pour l’évaluation d’un sarcome rétropéritonéal soupçonné. Toutefois, par le passé, certains ont suggéré que cette pratique puisse possiblement disséminer le cancer et causer une récidive locale, ce qui a limité la recherche sur le sujet. Ainsi, il existe un manque de littérature décrivant les paramètres optimaux pour effectuer une biopsie sécuritaire et efficace de ces lésions. Notre recherche en cours vise à identifier les paramètres de biopsie qui produisent une biopsie diagnostique sécuritaire et qualitative, tout en minimisant les complications et les risques de récidive locale, dans le but de fournir des soins uniformes et de haute qualité à tous les patients avec des lésions rétropéritonéales.

Retroperitoneal Sarcoma Care in 2021

Soft-tissue sarcomas are biologically heterogenous tumors arising from connective tissues with over 100 subtypes. Although sarcomas account for <1% of all adult malignancies, retroperitoneal sarcomas are a distinct subgroup accounting for <10% of all sarcomatous tumors. There have been considerable advancements in the understanding and treatment of retroperitoneal sarcoma in the last decade, with standard treatment consisting of upfront primary surgical resection. The evidence surrounding the addition of radiation therapy remains controversial. There remains no standard with regards to systemic therapy, including immunotherapy. Adjunctive therapy remains largely dictated by expert consensus and preferences at individual centers or participation in clinical trials. In this 2021 review, we detail the anatomical boundaries of the retroperitoneum, clinical characteristics, contemporary standard of care and well as recent advancements in retroperitoneal sarcoma care. Ongoing international collaborations are encouraged to advance our understanding of this complex disease

Prioritizing Melanoma Surgeries to Prevent Wait Time Delays and Upstaging of Melanoma during the COVID-19 Pandemic

Prompt diagnosis and surgical management of melanoma strongly impact prognosis. Considering the limited resources, emergency closures, and staffing shortages during the COVID-19 pandemic in Canada, our institution implemented a dedicated care pathway to prioritize cancer surgeries. We aim to assess whether this strategy was effective at preventing surgical wait time delays and upstaging of melanoma. We retrospectively collected data of patients aged ≥18 years with biopsy-proven primary melanoma who underwent wide local excision (WLE) ± sentinel lymph node biopsy (SLNB) between 1 March 2018–29 February 2020 (pre-pandemic) and 1 March 2020–22 March 2022 (pandemic). Patients with distant metastasis, recurrence, in situ disease, and unknown primary were excluded. Wait time from consult to surgery, tumour (T) and nodal (N) stage, and overall stage were collected. Results: We included 419 patients [pre-pandemic (n = 204) and pandemic (n = 215)]. Median wait time (days) [interquartile range] to surgery was 36 [22–48] pre-pandemic and 35 [24–49] during the pandemic (p = 0.888). There were no differences found in T stage (p = 0.060), N stage (p = 0.214), or overall melanoma stage (p = 0.192). We highlight the importance of streamlining melanoma surgery during a pandemic. As the need arises to meet surgical backlogs including benign surgery, dedicated cancer surgery should maintain a priority to not negatively affect cancer outcomes

Data Dissemination of the Role of Neoadjuvant Radiation in Retroperitoneal Sarcoma: A CTOS and CSSO Survey

Consensus guidelines call for complete resection of retroperitoneal sarcoma with consideration of neoadjuvant radiation for curative-intent treatment. The 15-month delay from the initial presentation of an abstract to the final publication of the STRASS trial results assessing the impact of neoadjuvant radiation led to a dilemma of how patients should be managed in the interim. This study aims to (1) understand perspectives regarding neoadjuvant radiation for RPS during this period; and (2) assess the process of integrating data into practice. A survey was distributed to international organizations including all specialties treating RPS. Eighty clinicians responded, including surgical (60.5%), radiation (21.0%) and medical oncologists (18.5%). Low kappa correlation coefficients on a series of clinical scenarios querying individual recommendations before and after initial presentation as an abstract indicate considerable change. Over 62% of respondents identified a practice change; however, most also noted discomfort in adopting changes without a manuscript available. Of the 45 respondents indicating discomfort with practice changes without a full manuscript, 28 (62%) indicated that their practice changed in response to the abstract. There was substantial variability in recommendations for neoadjuvant radiation between the presentation of the abstract and the publication of trial results. The difference in the proportion of clinicians describing comfort with changing practice based on the presentation of the abstract versus those that had done so shows that indications for proper integration of data into practice are not clear. Endeavors to resolve this ambiguity and expedite availability of practice-changing data are warranted

The Evolution of the Sentinel Node Biopsy in Melanoma

The growing repertoire of approved immune-checkpoint inhibitors and targeted therapy has revolutionized the adjuvant treatment of melanoma. While the treatment of primary cutaneous melanoma remains wide local excision (WLE), the management of regional lymph nodes continues to evolve in light of practice-changing clinical trials and dramatically improved adjuvant therapy. With large multicenter studies reporting no benefit in overall survival for completion lymph node dissection (CLND) after a positive sentinel node biopsy (SLNB), controversy remains regarding patient selection and clinical decision-making. This review explores the evolution of the SLNB in cutaneous melanoma in the context of a rapidly changing adjuvant treatment landscape, summarizing the key clinical trials which shaped current practice guidelines

The Evolution of the Sentinel Node Biopsy in Melanoma

The growing repertoire of approved immune-checkpoint inhibitors and targeted therapy has revolutionized the adjuvant treatment of melanoma. While the treatment of primary cutaneous melanoma remains wide local excision (WLE), the management of regional lymph nodes continues to evolve in light of practice-changing clinical trials and dramatically improved adjuvant therapy. With large multicenter studies reporting no benefit in overall survival for completion lymph node dissection (CLND) after a positive sentinel node biopsy (SLNB), controversy remains regarding patient selection and clinical decision-making. This review explores the evolution of the SLNB in cutaneous melanoma in the context of a rapidly changing adjuvant treatment landscape, summarizing the key clinical trials which shaped current practice guidelines