Poly(ADP-ribose) polymerase inhibitors in combination with anti-angiogenic agents for the treatment of advanced ovarian cancer.

Homologous recombination deficiency and VEGF expression are key pathways in high-grade ovarian cancer. Recently, three randomized practice changing trials were published: the PAOLA-1, PRIMA and VELIA trials. The use of PARP inhibitors (PARPi) following chemotherapy has become standard of care in first line. Combination of PARPi with anti-angiogenic agents has demonstrated synergistic activity in preclinical study. This review summarizes the body of evidence supporting the efficacy and safety of the combination of PARPi and anti-angiogenic drugs in first-line homologous recombination deficiency high-grade ovarian cancer leading to US FDA and EMA approvals. This double maintenance is supported by: a large benefit with bevacizumab + olaparib compared with olaparib alone, a rationale for additive effect, and a good safety and cost-effective profile.

Lay abstract Ovarian cancers often present difficulties to repair their DNA and are highly vascularized tumors. Recently, three randomized practice changing trials were published: the PAOLA-1, PRIMA and VELIA trials. They use one type of therapy to target the difficulty of ovarian cancer to repair their DNA which is called poly(ADP-ribose) polymerase inhibitor. This type of therapy has become standard of care after chemotherapy. In this review, we discuss the advantage of combining anti-angiogenic agents to poly(ADP-ribose) polymerase inhibitors to target the fact that tumors are highly vascularized. First, data from laboratory suggest synergistic activity of the combination. Then, clinical data are also in favor of the combination due to additive efficacy, and a good safety and cost-effective profile.

Diabetes Distress and Illness Perceptions in Tunisian Type 2 Diabetes Patients.

Purpose: Diabetes distress (DD) refers to the negative emotions and burden of living with diabetes. Illness perceptions are among the factors that can influence self-management and psychological distress in diabetics. This study aimed to determine the prevalence and the associated factors of DD in Tunisian patients with type 2 diabetes mellitus. We also studied the relationship between DD and illness perceptions in diabetics. Patients and Methods: This was a cross-sectional study conducted among individuals with type 2 diabetes, followed up at the outpatient endocrinology unit at the Hedi Chaker University Hospital, Tunisia. DD was assessed using the Diabetes Distress Scale (DDS-17). The Brief Illness Perception Questionnaire (Brief-IPQ) was used to assess diabetes illness perceptions. Multivariate logistic regression was used to determine independent factors associated with the presence of DD. Results: A total of 103 patients were recruited. The mean age was 59.31 (±10.83) years; 54.4% were female. In total, 70.9% had DD. Using regression analysis, we demonstrated that the illness perceptions of personal control, HbA1C, absence of comorbidities, lower age at diabetes diagnosis, and socioeconomic status were significantly associated with DD. Conclusion: This study sheds light on the high prevalence of DD among patients with type 2 diabetes in Tunisia. Illness perception-focused psychological intervention would be efficacious in reducing diabetes distress in patients with type 2 diabetes mellitus.

Low-Grade Uterine Leiomyosarcoma Is Highly Sensitive to Hormonal Treatment.

PURPOSE: According to the World Health Organization classification system, uterine leiomyosarcomas (ULMS) are high-grade. A diagnosis of smooth-muscle tumors of uncertain malignant potential (STUMP) is made when Stanford Criteria for ULMS are not met. When a STUMP recurs, the tumor is diagnosed as ULMS and medical treatment is the same as for ULMS. In recent years, some sarcoma centers valued the less aggressive clinical behavior of several recurring STUMP and, given their expression of estrogen and progesterone receptors, started to treat them with hormonal therapy. EXPERIMENTAL DESIGN: This was a retrospective cohort analysis conducted at three referral centers joining the Leiomyosarcoma Foundation Roundtable. We selected all cases of uterine smooth muscle tumors consistent with STUMP and treated with hormonal therapy. RESULTS: 27 consecutive patients were identified. Median age at diagnosis was 43 years. Stage was IA-IB in more than 70% of patients. In these patients, median time to relapse was 62 months. Sites of first relapses were mostly pelvis and peritoneum (76%). After a median follow-up of 49 months, 14 patients (52%) had a partial response while 10 (37%) had a minor response or stable disease. Median time to progression was not reached. CONCLUSIONS: We observed a response or long-term stability rate on hormonal therapy in the 90% range; in all cases the time to relapse was significantly longer than in ULMS and in most cases the relapse was abdominal. On the basis of these findings, we conclude that a proportion of patients with uterine smooth muscle neoplasms actually present with a "low-grade ULMS."