Pancreatic Cancer: Beyond Brca Mutations.

Pancreatic cancer is the fourth-leading cause of cancer-related deaths worldwide. The outcomes in patients with pancreatic cancer remain unsatisfactory. In the current review, we summarize the genetic and epigenetic architecture of metastatic pancreatic cancer beyond the BRCA mutations, focusing on the genetic alterations and the molecular pathology in pancreatic cancer. This review focuses on the molecular targets for the treatment of pancreatic cancer, with a correlation to future treatments. The potential approach addressed in this review may lead to the identification of a subset of patients with specific biological behaviors and treatment responses.

Arthralgia in patients with ovarian cancer treated with bevacizumab and chemotherapy.

BACKGROUND: Chemotherapy with carboplatin, paclitaxel, and bevacizumab is the standard therapy for patients with advanced stage ovarian cancer wild-type BRCA after primary surgery. The most frequent side effects of bevacizumab in this setting are hypertension, thrombosis, hemorrhage, and proteinuria, while arthralgia has been poorly described. OBJECTIVE: To examine the incidence, duration, and reversibility of arthralgia. PATIENTS AND METHODS: A retrospective analysis was performed to describe the occurrence and outcome of arthralgia in 114 patients with advanced ovarian cancer, given first-line treatment with a combination of carboplatin, paclitaxel, and bevacizumab. Statistical analysis was performed to investigate a possible prognostic role of arthralgia, with progression-free survival as endpoint. RESULTS: 47 of 114 patients (41%) developed arthralgia during therapy. All patients had grade 1 or grade 2 arthralgia. Toxicity persisted after the end of bevacizumab in 17/47 patients (36%). Median progression-free survival for patients without arthralgia was 18 months (95% CI 14 to 24) compared with 29 months (95% CI 21 to not reached) for patients experiencing arthralgia (p=0.03). In order to avoid possible biases related to treatment duration, a multivariable Cox proportional hazards model including toxicity as a time dependent variable and age, stage, and residual disease after primary surgery was performed. In this model no variable showed a statistically significant association with progression-free survival. CONCLUSION: A high incidence of arthralgia (41%) was found and although rogression-free survival was worse for those patients who developed arthralgia, this was not maintained on multivariate analysis. Guidelines for treatment of this adverse event are needed.

Immunotherapy in ovarian, endometrial and cervical cancer: State of the art and future perspectives.

The tumors of the female genital tract represent a leading cause of morbidity and mortality among women worldwide. Substantial progresses have been made in ovarian cancer, with the increasing knowledge about BRCA mutated tumors and the recent development of PARP inhibitors, and in cervical cancer, thanks to extensive screening and widespread of vaccination against Human Papilloma Virus. Nevertheless many needs remain unmet, advanced stage diseases are still incurable and cervical and endometrial carcinoma, as well as platinum-resistant ovarian carcinoma, can certainly be classifiable among the cancers with poor sensitivity to conventional chemotherapy. Immunotherapy, including a number of approaches, checkpoint inhibitors, adoptive cellular transfer, vaccines, has experienced a remarkable growth in the last few years and it is already an available option in melanoma, lung and renal malignancies. We reviewed the main findings about the immune microenvironment in ovarian, endometrial and cervical cancer with a special focus on the clinical data, the therapeutic implications and the most promising novel agents.

2D and 3D strain for detection of subclinical anthracycline cardiotoxicity in breast cancer patients: a balance with feasibility.

AIMS: 2D echocardiography is limited for identifying chemotherapy-related cardiotoxicity. This study compared standard echo, 2D, and 3D speckle tracking echocardiography (STE) for detection of subclinical anthracycline (ANT) cardiotoxicity in breast cancer patients. METHODS AND RESULTS: One-hundred consecutive breast cancer patients free of cardiac symptoms were treated by multiple protocols including ANT and cyclophosphamide and/or 5-fluorouracil for 3-4 cycles. Both before and after treatment, patients underwent standard echo, 2D STE-derived left ventricular (LV) global longitudinal strain (GLS), 3D volumetric echo and 3D STE with measurements of GLS, global circumferential strain (GCS), global area strain (GAS), and global radial strain (GRS). The follow-up period from the beginning of cancer therapy was 129 ± 18 days. All patients completed the chemotherapy cycles, without experiencing symptoms/signs of heart failure. 2D ejection fraction (EF) was not significantly changed after treatment, whereas E/e' ratio was higher than baseline (from 6.9 ± 2.2 to 7.3 ± 2.1, P = 0.006). 2D GLS was reduced after treatment (from -22.2 ± 2.3% to - 20.1 ± 6.6%, P = 0.004). 3D derived LV end-systolic volume was increased (P < 0.01) and 3D EF (from 62.4 ± 6.5% to 60.3 ± 7.3%, P < 0.01), 3D GLS (P < 0.001) GRS (P < 0.002), GCS, and GAS (both P < 0.0001) were reduced after ANT. Post-ANT 2D GLS was feasible in 90%, 3D EF in 66%, and 3D STE in 60% of patients. CONCLUSIONS: Our study demonstrates potential superiority but also suboptimal feasibility of 3D EF and 3D strain in diagnosing subclinical ANT cardiotoxicity in breast cancer patients. 2D GLS is superior to standard echo and presents a good feasibility. E/e' ratio also offers advantages in revealing cardiotoxicity.