The Impact of Addition of Consolidation Chemotherapy to Standard Cisplatin-Based Chemoradiotherapy in Uterine Cervical Cancer: Matter of Distant Relapse.

BACKGROUND: Treatment of advanced uterine cervical cancer has advanced little in the last 15 years. Although two phase III trials showed survival benefit with the addition of consolidation chemotherapy (CT) after cisplatin-based chemoradiotherapy (RTCT), it is not considered standard of care. We aimed to evaluate the benefit of consolidation CT compared to no additional treatment in patients treated with RTCT. METHODS: This is a retrospective study including 186 patients with FIGO stage IB2, IIA2, or IIB to IVB (paraaortic lymph nodes only) uterine cervical cancer who were treated with standard RTCT alone or RTCT followed by consolidation CT. Overall survival (OS), progression free survival (PFS), and the risk of distant and local relapses were compared between the two treatment groups. RESULTS: At 3 years OS was 91% versus 82.3% (p=0.027), PFS 84.3% versus 54.4% (p=0.047), and distant metastasis free survival (DMFS) 80.4% versus 62.5% (p=0.027) in favor of the consolidation CT group. Multivariate analysis confirmed the benefit of consolidation CT. There was no difference in locoregional free survival (LRFS). Positive lymph node was related to a higher risk of distant relapse. In the lymph node positive subgroup consolidation CT resulted in longer OS (p=0.050), PFS (p=0.014), and DMFS (p=0.022); in the lymph node negative subgroup there was no benefit from consolidation CT. CONCLUSIONS: Use of consolidation CT resulted in longer OS and PFS, mostly due to control of distant relapses. Patients at higher risk of distant relapse showed the greatest benefit. This data generates a hypothesis that could help to better select patients to consolidation CT.

Risk factors for pelvic and distant recurrence in locally advanced cervical cancer.

OBJECTIVE: Despite the benefits of concomitant radiotherapy and cisplatin for locally advanced cervical cancer, recurrence rates remain high. New treatment strategies such as consolidation chemotherapy and different concomitant chemotherapy combinations have been tested in recent years. Identification of the best candidates for each treatment strategy could optimize results. STUDY DESIGN: A retrospective review of data from 127 patients with locally advanced cervical cancer (International Federation of Gynecology and Obstetrics Stages IIB-IVA), treated at a single institution from 2005 to 2014. Risk factors for loco-regional and systemic recurrence, and prognostic factors for overall survival (OS) were analysed using Cox regression. Survival of patients treated with consolidation chemotherapy was compared with survival of patients not treated with consolidation chemotherapy in the role cohort and in a propensity-score-matched cohort. RESULTS: With a median follow-up time of 48.7 months, loco-regional-recurrence-free survival (LRFS), distant-metastasis-free survival (DMFS) and OS at 5 years were 76.6%, 54.0% and 63.0%, respectively. On multivariate analysis, tumour size ≥6 cm was associated with shorter LRFS [hazard ratio (HR) 5.18; 95% confidence interval (CI) 1.45-18.45; p = 0.011], and adenocarcinoma (HR 2.48; 95% CI 1.10-5.57; p = 0.028) and positive lymph nodes (HR 2.21; 95% CI 1.303-4.72; p = 0.041) were associated with shorter DMFS. Tumour size ≥6 cm was associated with shorter OS (HR 2.64; 95% CI 1.09-6.35; p = 0.031). Twenty-two patients were treated with consolidation chemotherapy; on univariate analysis, these patients had longer OS compared with patients who were not treated with consolidation chemotherapy (p = 0.043). In a propensity-score-matched cohort, patients treated with consolidation chemotherapy had longer DMFS and OS compared with patients who were not treated with consolidation chemotherapy, although the difference was not significant. CONCLUSIONS: Different risk factors are associated with loco-regional and distant metastases in patients with locally advanced cervical cancer, and could potentially lead to particular therapeutic strategies. Although the number of patients treated with consolidation chemotherapy in the study cohort was small, they seemed to live longer and to have better control of distant relapse then patients who were not treated with consolidation chemotherapy.

Melatonin decreases breast cancer metastasis by modulating Rho-associated kinase protein-1 expression.

The occurrence of metastasis, an important breast cancer prognostic factor, depends on cell migration/invasion mechanisms, which can be controlled by regulatory and effector molecules such as Rho-associated kinase protein (ROCK-1). Increased expression of this protein promotes tumor growth and metastasis, which can be restricted by ROCK-1 inhibitors. Melatonin has shown oncostatic, antimetastatic, and anti-angiogenic effects and can modulate ROCK-1 expression. Metastatic and nonmetastatic breast cancer cell lines were treated with melatonin as well as with specific ROCK-1 inhibitor (Y27632). Cell viability, cell migration/invasion, and ROCK-1 gene expression and protein expression were determined in vitro. In vivo lung metastasis study was performed using female athymic nude mice treated with either melatonin or Y27832 for 2 and 5 wk. The metastases were evaluated by X-ray computed tomography and single photon emission computed tomography (SPECT) and by immunohistochemistry for ROCK-1 and cytokeratin proteins. Melatonin and Y27632 treatments reduced cell viability and invasion/migration of both cell lines and decreased ROCK-1 gene expression in metastatic cells and protein expression in nonmetastatic cell line. The numbers of 'hot' spots (lung metastasis) identified by SPECT images were significantly lower in treated groups. ROCK-1 protein expression also was decreased in metastatic foci of treated groups. Melatonin has shown to be effective in controlling metastatic breast cancer in vitro and in vivo, not only via inhibition of the proliferation of tumor cells but also through direct antagonism of metastatic mechanism of cells rendered by ROCK-1 inhibition. When Y27632 was used, the effects were similar to those found with melatonin treatment.

Long-term cardiac changes in patients with systemic lupus erythematosus.

BACKGROUND: The aim of this study was evaluate the late-onset repercussions of heart alterations of patients with systemic lupus erythematosus (SLE) after a 13-year follow up. METHODS: A historical prospective study was carried out involving the analysis of data from the charts of patients with a confirmed diagnosis of lupus in follow up since 1998. The 13-year evolution was systematically reviewed and tabulated to facilitate the interpretation of the data. RESULTS: Forty-eight patient charts were analyzed. Mean patient age was 34.5 ± 10.8 years at the time of diagnosis and 41.0 ± 10.3 years at the time of the study (45 women and 3 men). Eight deaths occurred in the follow-up period (two due to heart problems). Among the alterations found on the complementary exams, 46.2% of cases demonstrated worsening at reevaluation and four patients required a heart catheterization. In these cases, coronary angioplasty was performed due to the severity of the obstructions and one case required a further catheterization, culminating in the need for surgical myocardial revascularization. CONCLUSION: The analysis demonstrated progressive heart impairment, with high rates of alterations on conventional complementary exams, including the need for angioplasty or revascularization surgery in four patients. These findings indicate the need for rigorous cardiac follow up in patients with systemic lupus erythematosus.