The Role of Cyclin-Dependent Kinase 4/6 Inhibitors Treatment in Oligometastatic Breast Cancer: A Case Report on a Possible Curative Intent Strategy.

A small but important subset of patients with metastatic breast cancer has an oligometastatic disease. Some of these patients are highly responsive to systemic therapy and have the potential to achieve complete remission with treatment. However, it remains to be clarified the best locoregional and systemic treatment strategy for such patients and what features can determine whose patients are the best candidates. We also don't know what will be the role of cyclin-dependent kinase 4/6 inhibitors in those cases. We report the case of a 41-year-old woman with HR-positive/HER2-negative oligometastatic breast cancer who, after an excellent response to systemic treatment with palbociclib, anastrozole, and goserelin, underwent breast surgery and liver metastasectomy. After completing three years of systemic treatment, the CDK inhibitor was discontinued, maintaining the hormone therapy. The patient remained under regular follow-up with no evidence of disease after eight months.

Recurrent Ovarian Cancer with BRCAness Phenotype: A Treatment Challenge.

INTRODUCTION: Ovarian cancer is a leading cause of death among women with gynecologic malignancies. The relapse rate is high after platinum-based therapy, with the effectiveness of subsequent treatment lines decreasing over time. Recent data suggest the benefit of maintenance therapy with niraparib in platinum-sensitive recurrent disease. CASE PRESENTATIONS: We report a case series of five women with advanced ovarian cancer and BRCAness phenotype who responded favorably, and in some cases with long-term response, to maintenance therapy with niraparib. Toxicities were as expected and generally manageable. Two patients developed grade 2/3 hematological toxicity, which resolved with treatment suspension and subsequent dose reductions, and one patient reported a rare skin toxicity while responding to full-dose niraparib treatment, which was controlled with photoprotection and sunscreen. DISCUSSION AND CONCLUSIONS: This case series highlights the role of PARP1/2 inhibitors as a new standard of care as maintenance therapy for recurrent platinum-sensitive high-grade ovarian cancer, irrespective of BRCA status.

Metastatic BRAF V600E-Mutated Thyroid Carcinoma: Molecular/Genetic Profiling Brings a New Therapeutic Option.

We describe a case of a 46-year-old woman diagnosed with localized PTC 20 years ago, having already undergone several treatments with iodine-131 and then treatment with lenvatinib for metastatic disease, to which she developed intolerance. In 2020, in addition to pleural, thoracic, and abdominal lymph node metastasis, progression with symptomatic vertebral bone metastasis was detected, which led to the equation of new therapeutic options. In this context, a genetic/molecular test was carried out, which identified the BRAF V600E mutation and enabled the start of treatment with dabrafenib/trametinib since June 2020. This treatment allowed functional gain, symptomatic relief, and stabilization of the disease. It demonstrates how, in rare tumors, the personalized medicine approach can bring new treatment possibilities.

Hypertension and proteinuria as clinical biomarkers of response to bevacizumab in glioblastoma patients.

INTRODUCTION: Arterial hypertension and proteinuria are common side effects of antiangiogenic treatment and might represent a biomarker of response in patients with glioblastoma. The aim of this study was to assess the impact of these side effects in predicting therapeutic response to second line chemotherapy with bevacizumab. METHODS: We evaluated clinical and survival data of glioblastoma patients who underwent treatment with bevacizumab after progression under temozolomide, at CHUSJ between 2010 and 2017. We analysed treatment-related arterial hypertension, proteinuria grade, thrombotic and haemorrhagic events during treatment. Overall survival (OS) and progression free survival (PFS) under bevacizumab were calculated according to the Kaplan-Meier method. Multivariate analysis was performed using Cox proportional hazards method. RESULTS: We evaluated 140 patients. Arterial hypertension and proteinuria occurred in 23 (16.3%) and 17 (12.1%) patients, respectively. PFS during treatment with bevacizumab was 12 months (95% CI 7.9-16.1) in the hypertensive group and 4 months (95% CI 3.2-4.8) in the normotensive group (p = 0.005). Patients with proteinuria had a PFS of 10 months (95% CI 4.9-15.0) versus 4 months (95% CI 3.4-4.8) in patients without proteinuria (p = 0.002). Multivariate analysis revealed hypertension and proteinuria as independent prognostic factors of PFS and OS. CONCLUSION: Our data suggest that hypertension and proteinuria can be effective predictors of response to antiangiogenic therapy in recurrent glioblastoma and are associated with longer disease control.

Second-Line Chemotherapy in Recurrent Glioblastoma: A 2-Cohort Study.

BACKGROUND: Glioblastoma (GB) is the most common malignant primary central nervous system tumor in adults. Standard-of-care therapy includes surgical resection, radiotherapy and temozolomide, but nearly all patients experience disease progression. The purpose of this study was to describe 2 cohorts of patients with recurrent GB submitted to second-line treatment with procarbazine/lomustine/vincristine (PCV) or bevacizumab/irinotecan (BI). MATERIAL AND METHODS: Retrospective analysis of GB patients treated in our center with PCV or BI, after progression with temozolomide, between 2004 and 2012. RESULTS: Among 60 patients, 41 were treated with BI and 19 with PCV. According to the Macdonald criteria, the overall response rate in the BI group was 66% (n = 27) while it was 11% (n = 2) in the PCV group. The median progression-free survival was 5 and 3 months in the BI and PCV group, respectively. The median overall survival (OS) since second-line chemotherapy was 9 months in the BI group and 5 months in the PCV group. The latter group had a worse toxicity profile (grade 3-4: 52.6% vs. 22.0%; grade 1-2: 89.5% vs. 68.3%). CONCLUSIONS: The BI cohort had higher response rates, almost twice the OS and a lower degree of toxicity in contrast to the PCV group. The small number of patients and historical cohorts limits these comparisons.

Downregulation of RKIP is associated with poor outcome and malignant progression in gliomas.

Malignant gliomas are highly infiltrative and invasive tumors, which precludes the few treatment options available. Therefore, there is an urgent need to elucidate the molecular mechanisms underlying gliomas aggressive phenotype and poor prognosis. The Raf Kinase Inhibitory protein (RKIP), besides regulating important intracellular signaling cascades, was described to be associated with progression, metastasis and prognosis in several human neoplasms. Its role in the prognosis and tumourigenesis of gliomas remains unclear. In the present study, we found that RKIP protein is absent in a low frequency (10%, 20/193) of glioma tumors. Nevertheless, the absence of RKIP expression was an independent prognostic marker in glioma. Additionally, by in vitro downregulation of RKIP, we found that RKIP inhibition induces a higher viability and migration of the cells, having no effect on cellular proliferation and angiogenesis, as assessed by in vivo CAM assay. In conclusion, this is the largest series studied so far evaluating the expression levels of this important cancer suppressor protein in glioma tumors. Our results suggest that in a subset of tumors, the absence of RKIP associates with highly malignant behavior and poor survival of patients, which may be a useful biomarker for tailored treatment of glioma patients.

Prognostic value of MGMT promoter methylation in glioblastoma patients treated with temozolomide-based chemoradiation: a Portuguese multicentre study.

Glioblastoma (GBM) is the most common and aggressive primary brain tumor. The identification of novel molecular prognostic markers of GBM has recently been an area of great interest in neuro-oncology. The methylation status of the MGMT gene promoter is currently a promising molecular prognostic marker, but some controversial data have precluded its clinical use. We analyzed MGMT methylation by methylation-specific PCR in 90 GBM patients from four Portuguese hospitals, uniformly treated with radiotherapy combined with concomitant and adjuvant temozolomide (Stupp protocol). The Kaplan-Meier method was used to construct survival curves, and the log-rank test and a Cox-regression model were used to analyze patient survival. The methylation status of MGMT was successfully determined in 89% (80/90) of the tumors. The frequency of tumoral MGMT promoter methylation was 47.5%. The median overall survivals (OSs) were 16 months (95% CI 12.2-19.8) and 13 months (95% CI 13.3-18.7) for patients whose tumors had a methylated or unmethylated MGMT, respectively. Univariate and multivariate analyses did not show any statistically significant association between MGMT methylation status and patient OS (P=0.583 by the log-rank test; P=0.617 by the Cox-regression test) or progression-free survival (P=0.775 by the log-rank test; P=0.691 by the Cox-regression test). None of the patient clinical features were significantly correlated with survival. This is the first study to report the frequency of MGMT methylation among Portuguese GBM patients. Our data did not show statistically significant associations between MGMT promoter methylation and the outcome of GBM patients treated with temozolomide. Additional robust prospective studies are warranted to clarify whether the MGMT status should be used in clinical decisions.