Eirini Thanopoulou

The safety profile of imatinib in CML and GIST: long-term considerations

Imatinib mesylate is considered the standard first-line systemic treatment for patients with chronic myeloid leukaemia (CML) and gastrointestinal stromal tumour (GIST) by targeting BCR-ABL and c-KIT tyrosine kinases, respectively. Indeed, imatinib has substantially changed the clinical management and improved the prognosis of both diseases. Treatment with imatinib is generally well tolerated, and the risk for severe adverse effects is low, generally occurring during the early phase of treatment and correlating with imatinib dose, phase of disease and patient’s characteristics. This article summarises recent data on safety profile of imatinib for the treatment of CML and GIST, including long-term side effects. Prolonged treatment with imatinib in both diseases demonstrates excellent tolerability. There are few significant concerns and those that have emerged, like cardiotoxicity, have far turned out to be exaggerated.

Tumour heterogeneity and immune-modulation

Highlights • Intratumour heterogeneity (ITH) has been demonstrated in various tumour types.• Distinct clonal subpopulations can exist within different regions of a tumour.• ITH has evident implications for cancer diagnosis and treatment.• There is increasing evidence for the association between ITH and drug resistance.• ITH may allow the effective use of immunotherapeutics against tumour neo-antigens.

Hormonal therapy in gynecological sarcomas

Gynecological sarcomas are rare, constituting 3–5% of uterine malignancies. Endometrial stromal sarcomas and some uterine leiomyosarcomas are characterized by estrogen receptor (ER) and progesterone receptor (PgR) expression with variable impact on their clinical behavior and potential response to systemic therapies. A variety of hormonal treatments have been tested, since they act as targeted treatment against ER and PgR and have a tolerable side effect profile, which allows them to be administered for prolonged periods. Their role has been studied more extensively in endometrial stromal sarcomas, as the majority of cases are ER/PgR positive, while recently, an emerging role for hormonal manipulation has been described in ER/PgR-positive uterine leiomyosarcomas. Owing to the rarity and heterogeneous nature of uterine sarcomas, current treatment recommendations are based on small retrospective studies and case reports. This review comprises a critical appraisal of the existing data regarding hormonal manipulation in uterine sarcomas and attempts to make recommendations for endocrine treatments in specific settings, as well as suggest targets/medications for future research.

Potential role of phytoestrogens in the pathophysiology of fibromatosis

Fibromatosis also known as desmoid tumour is a rare monoclonal fibroblastic proliferative disease, classified as superficial or deep [1]. Active systemic treatments, in case local treatment fails to control the disease, include antiinflammatory drugs and antiestrogens (e.g. tamoxifen) [1]. The physiologic mechanism that underlies the pharmacological response of fibromatosis to antiestrogens is the nearly uniform expression of estrogen receptor b (ERb) [2], though alternative pathways leading to progression exist [3]. Clinically it has been shown that fibromatosis is hormonally sensitive, as the incidence is associated with pregnancy and use of contraceptives and hormonal replacement treatment [2, 4]. We report the effect of vegetarian diet on the development of fibromatosis. A 23-year-old lady with fibromatosis of the right inguinal region presented to our department in 2010. As she had been on combined oral contraceptive for almost 3 years, it was discontinued and she was started on diclofenac. Two months later, tamoxifen 40 mg daily was added, but 10 months later, the disease progressed. At that time, it was found that she had adopted a vegetarian diet 2 years before the diagnosis. It was suggested with dietician guidance to modify her daily intake of products containing phytoestrogens. Three weeks later, her fibromatosis had apparently improved with no signs of active inflammation along with improvement in function and pain control. Eventually, 6 weeks later, she progressed and liposomal doxorubicin was commenced. Phytoestrogens are plant-derived compounds, structurally similar to estrogens that can induce estrogenic responses in humans [5]. Isoflavones, one of the main classes, are found predominately in soya products, which constitute an integral part of a vegetarian diet. Phytoestrogens have been shown to Annals of Oncology letters to the editor