Phase II trial of tamoxifen and goserelin in recurrent epithelial ovarian cancer

Endocrine therapy is a recognised option in the treatment of chemo-resistant ovarian cancer. We conducted a nonrandomised phase II evaluation of combination endocrine therapy with tamoxifen and goserelin in patients with advanced ovarian cancer that had recurred following chemotherapy. In total, 26 patients entered the study, of which 17 had platinum-resistant disease. The median age was 63 years and enrolled patients had received a median of three chemotherapy regimens prior to trial entry. Patients were given oral tamoxifen 20 mg twice daily on a continuous basis and subcutaneous goserelin 3.6 mg once a month until disease progression. Using the definition of endocrine response that included patients with stable disease (SD) of 6 months or greater, the overall response rate (clinical benefit rate) was 50%. This included one complete response (CR) (3.8%), two partial responses (PR) (7.7%) and 10 patients with SD (38.5%). The median progression-free interval (PFI) was 4 months (95% CI 2.4–9.6) while the median overall survival (OS) was 13.6 months (95% CI 5.5–30.6). Four patients received treatment for more than 2 years (range 1–31) and one of them is still on treatment. In none of the four patients was there any evidence of recurrent or cumulative treatment related toxicity. Treatment-limiting toxicity was not seen in any of the study population. Endocrine data demonstrated a marked suppression of luteinising hormone (LH) and follicle-stimulating hormone (FSH) to less than 4% of baseline values. No consistent correlation could be established between LH/FSH suppression and tumour response. Likewise no relationship was observed between Inhibin A/B and pro-alpha C levels and tumour response. Inhibin is unlikely to be a useful surrogate marker for response in locally advanced or metastatic ovarian cancer. Combination endocrine therapy with tamoxifen and goserelin is an active regimen in platinum-resistant ovarian cancer patients. Hormonal therapy is advantageous in its relative lack of toxicity, ease of administration and tolerability, thus making it suitable for patients with heavily pretreated disease, compromised bone marrow function and other comorbid conditions that contraindicate cytotoxic therapy as well as in patients with indolent disease

Multisocietal European consensus on the terminology, diagnosis, and management of patients with synchronous colorectal cancer and liver metastases:an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE

BACKGROUND: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases, with a focus on terminology, diagnosis, and management. METHODS: This project was a multiorganizational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis, and management. Statements were refined during an online Delphi process, and those with 70 per cent agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising 12 key statements.RESULTS: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term 'early metachronous metastases' applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour, the term 'late metachronous metastases' applies to those detected after 12 months. 'Disappearing metastases' applies to lesions that are no longer detectable on MRI after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards, and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways, including systemic chemotherapy, synchronous surgery, and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. CONCLUSION: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.</p

The multi-societal European consensus on the terminology, diagnosis and management of patients with synchronous colorectal cancer and liver metastases:an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE

Background: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases with a focus on terminology, diagnosis and management. Methods: This project was a multi-organisational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis and management. Statements were refined during an online Delphi process and those with 70% agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising twelve key statements. Results: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term “early metachronous metastases” applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour with “late metachronous metastases” applied to those detected after 12 months. Disappearing metastases applies to lesions which are no longer detectable on MR scan after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways including systemic chemotherapy, synchronous surgery and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. Conclusions: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases.</p

The multi-societal European consensus on the terminology, diagnosis and management of patients with synchronous colorectal cancer and liver metastases:an E-AHPBA consensus in partnership with ESSO, ESCP, ESGAR, and CIRSE

Background: Contemporary management of patients with synchronous colorectal cancer and liver metastases is complex. The aim of this project was to provide a practical framework for care of patients with synchronous colorectal cancer and liver metastases with a focus on terminology, diagnosis and management. Methods: This project was a multi-organisational, multidisciplinary consensus. The consensus group produced statements which focused on terminology, diagnosis and management. Statements were refined during an online Delphi process and those with 70% agreement or above were reviewed at a final meeting. Iterations of the report were shared by electronic mail to arrive at a final agreed document comprising twelve key statements. Results: Synchronous liver metastases are those detected at the time of presentation of the primary tumour. The term “early metachronous metastases” applies to those absent at presentation but detected within 12 months of diagnosis of the primary tumour with “late metachronous metastases” applied to those detected after 12 months. Disappearing metastases applies to lesions which are no longer detectable on MR scan after systemic chemotherapy. Guidance was provided on the recommended composition of tumour boards and clinical assessment in emergency and elective settings. The consensus focused on treatment pathways including systemic chemotherapy, synchronous surgery and the staged approach with either colorectal or liver-directed surgery as first step. Management of pulmonary metastases and the role of minimally invasive surgery was discussed. Conclusions: The recommendations of this contemporary consensus provide information of practical value to clinicians managing patients with synchronous colorectal cancer and liver metastases

Fibroblast heterogeneity in the cancer wound

Fibroblasts regulate the structure and function of healthy tissues, participate transiently in tissue repair after acute inflammation, and assume an aberrant stimulatory role during chronic inflammatory states including cancer. Such cancer-associated fibroblasts (CAFs) modulate the tumor microenvironment and influence the behavior of neoplastic cells in either a tumor-promoting or tumor-inhibiting manner. These pleiotropic functions highlight the inherent plasticity of fibroblasts and may provide new avenues to understand and therapeutically intervene in malignancies. We discuss the emerging themes of CAF biology in the context of tumorigenesis and therapy

Management of colorectal cancer presenting with synchronous liver metastases

Up to a fifth of patients with colorectal cancer (CRC) present with synchronous hepatic metastases. In patients with CRC who present without intestinal obstruction or perforation and in whom comprehensive whole-body imaging confirms the absence of extrahepatic disease, evidence indicates a state of equipoise between several different management pathways, none of which has demonstrated superiority. Neoadjuvant systemic chemotherapy is advocated by current guidelines, but must be integrated with surgical management in order to remove the primary tumour and liver metastatic burden. Surgery for CRC with synchronous liver metastases can take a number of forms: the 'classic' approach, involving initial colorectal resection, interval chemotherapy and liver resection as the final step; simultaneous removal of the liver and bowel tumours with neoadjuvant or adjuvant chemotherapy; or a 'liver-first' approach (before or after systemic chemotherapy) with removal of the colorectal tumour as the final procedure. In patients with rectal primary tumours, the liver-first approach can potentially avoid rectal surgery in patients with a complete response to chemoradiotherapy. We overview the importance of precise nomenclature, the influence of clinical presentation on treatment options, and the need for accurate, up-to-date surgical terminology, staging tests and contemporary management options in CRC and synchronous hepatic metastatic disease, with an emphasis on multidisciplinary care

Strategies to inhibit tumour associated integrin receptors: rationale for dual and multi-antagonists

YesThe integrins are a family of 24 heterodimeric transmembrane cell surface receptors. Involvement in cell attachment to the extracellular matrix, motility, and proliferation identifies integrins as therapeutic targets in cancer and associated conditions; thrombosis, angiogenesis and osteoporosis. The most reported strategy for drug development is synthesis of an agent that is highly selective for a single integrin receptor. However, the ability of cancer cells to change their integrin repertoire in response to drug treatment renders this approach vulnerable to the development of resistance and paradoxical promotion of tumor growth. Here, we review progress towards development of antagonists targeting two or more members of the RGD-binding integrins, notably αvβ3, αvβ5, αvβ6, αvβ8, α5β1, and αIIbβ3, as anticancer therapeutics

Cell Adhesion Molecules and Their Roles and Regulation in the Immune and Tumor Microenvironment

The immune system and cancer have a complex relationship with the immune system playing a dual role in tumor development. The effector cells of the immune system can recognize and kill malignant cells while immune system-mediated inflammation can also promote tumor growth and regulatory cells suppress the anti-tumor responses. In the center of all anti-tumor responses is the ability of the immune cells to migrate to the tumor site and to interact with each other and with the malignant cells. Cell adhesion molecules including receptors of the immunoglobulin superfamily and integrins are of crucial importance in mediating these processes. Particularly integrins play a vital role in regulating all aspects of immune cell function including immune cell trafficking into tissues, effector cell activation and proliferation and the formation of the immunological synapse between immune cells or between immune cell and the target cell both during homeostasis and during inflammation and cancer. In this review we discuss the molecular mechanisms regulating integrin function and the role of integrins and other cell adhesion molecules in immune responses and in the tumor microenvironment. We also describe how malignant cells can utilize cell adhesion molecules to promote tumor growth and metastases and how these molecules could be targeted in cancer immunotherapy.Peer reviewe