Optimal management of recurrent ovarian cancer (ROC) remains an area of uncertainty. An estimated 85% of patients with epithelial ovarian cancer who achieve a full remission following first-line ...therapy will develop recurrent disease and median survival for these patients' ranges from 12 months to 24 months. Many patients receive several lines of treatment following recurrence and, although each subsequent line of therapy is characterized by shorter disease-free intervals, decisions about the most appropriate treatment is complex. Areas covered: This review focuses on chemotherapy, surgery and emerging biologic agents that present a therapeutic option for patients with ROC. Expert commentary: Recurrent ovarian cancer is not curable. The goals of therapy should focus on palliation of cancer-related symptoms, extension of life, and maintenance of quality of life. Patients with platinum-sensitive ovarian cancer should have their recurrence treated with a platinum-based agent. For patients whose cancer progresses after platinum retreatment and for those with platinum-resistant disease, numerous other non-platinum combination and targeted therapies have been shown to be effective in palliating cancer-related symptoms and extending life.
Purpose
The purpose of this study was to assess the prognostic role and the perioperative outcomes of conization performed before radical hysterectomy in early-stage cervical carcinoma.
Methods
This ...multicenter, retrospective observational cohort study included patients with FIGO 2009 stage IB1 cervical carcinoma treated with radical hysterectomy between June 2004 and June 2019. Patients were divided into two groups according to conization before radical surgery. One-to-one case–control matching was used to adjust the baseline characteristics.
Results
A total of 332 patients were included after propensity matching (166, 50% in each group). Twenty-four of 166 (14.4%) and 142 of 166 (85.6%) conization patients had negative and positive surgical margins on the conization specimen, respectively. No difference in intra- and postoperative complications was noted between the two groups (
p
= 0.542 and
p
= 0.180, respectively). Patients undergoing conization before radical hysterectomy received less adjuvant treatment (
p
< 0.001) and had a better 5-year disease-free survival (DFS) than patients who did not receive conization (89.8% vs. 80.0%, respectively;
p
= 0.010). No difference in 5-year overall survival (OS) (97.1% vs. 91.4%, respectively;
p
= 0.114) or recurrence pattern (
p
= 0.115) was reported between the two groups. Factors independently related to higher risk of recurrence were pathologic tumor diameter >20 mm and no conization before radical hysterectomy (
p
= 0.011 and
p
= 0.018, respectively). The only independent variable influencing OS was pathologic tumor diameter >20 mm (
p
= 0.020).
Conclusions
Conization before radical hysterectomy was associated with improved DFS and lower probability of receiving adjuvant treatment. No difference in perioperative complications and OS was evident. Tumor diameter >20 mm was found to be the only independent risk factor affecting OS in both groups.
Purpose
The aim of this study is to determine if radiomics features extracted from staging magnetic resonance (MR) images could predict 2-year long-term clinical outcome in patients with locally ...advanced cervical cancer (LACC) after neoadjuvant chemoradiotherapy (NACRT).
Materials and methods
We retrospectively enrolled patients with LACC diagnosis who underwent NACRT followed by radical surgery in two different institutions.
Radiomics features were extracted from pre-treatment 1.5 T T2w MR images.
The predictive performance of each feature was quantified in terms of Wilcoxon–Mann–Whitney test. Among the significant features, Pearson correlation coefficient (PCC) was calculated to quantify the correlation among the different predictors. A logistic regression model was calculated considering the two most significant features at the univariate analysis showing the lowest PCC value.
The predictive performance of the model created was quantified out using the area under the receiver operating characteristic curve (AUC).
Results
A total of 175 patients were retrospectively enrolled (142 for the training cohort and 33 for the validation one).
1896 radiomic feature were extracted, 91 of which showed significance (
p
< 0.05) at the univariate analysis. The radiomic model showing the highest predictive value combined the features calculated starting from the gray level co-occurrence-based features. This model achieved an AUC of 0.73 in the training set and 0.91 in the validation set.
Conclusions
The proposed radiomic model showed promising performances in predicting 2-year overall survival before NACRT. Nevertheless, the observed results should be tested in larger studies with consistent external validation cohorts, to confirm their potential clinical use.
Background
Recently, it was reported that minimally invasive surgery (MIS) has a negative impact on early-stage cervical cancer (ECC) patient survival. At the same time, advantages of MIS regarding ...quality of life and low rate of intra- and postoperative complications are well known. Therefore, it is essential to select patients who may benefit from MIS without worsening their oncologic outcomes. The aim of this study is to investigate which pathological factors could guide surgeons’ choice about the best approach in ECC.
Patients and Methods
Patients with 2009 FIGO stage from IA1 with lymphovascular space invasion (LVSI) to IB1/IIA1 treated by open or laparoscopic surgery were judged eligible for the study. Disease-free survivals (DFS) of both approaches were tested in subgroups, defined according to histology, tumor size, grading, LVSI, parametrial involvement, and nodal status.
Results
A total of 423 patients were enrolled (217 in the open and 206 in the laparoscopic group). No difference between open surgery and laparoscopy was found among subgroups defined according to histology, grading, LVSI, parametrial involvement, or nodal status. Among patients with tumor > 20 mm, laparoscopy showed a significantly higher relapse risk hazard ratio (HR): 2.103,
p
= 0.030. Among patients with tumor
<
20 mm, laparoscopy showed DFS superimposable to open surgery (HR: 0.560,
p
= 0.128).
Conclusions
Tumor size of 20 mm appeared as the only independent discrimination criterion in patients whose prognosis is affected by surgical approaches.
Purpose
Reporting the perioperative and survival outcomes of vaginectomy with respect to a matched series of pelvic exenteration (PE) in women with isolated recurrent cervical cancer.
Methods
The ...records of vaginal recurrent cervical cancer patients admitted at Fondazione Policlinico “Agostino Gemelli” IRCCS in Rome from January 2010 to June 2019 were retrospectively analyzed. A propensity-matched score analysis was performed by age, clinical stage, disease-free interval, and R0 resection. Postsurgical complications and survival rates were evaluated.
Results
Fifteen women underwent vaginectomy, and 30 patients were submitted to PE. No statistical differences were observed between the two groups at baseline characteristics. The vaginectomy procedures were successfully performed in all women, and no case required conversion to PE. Moreover, a higher rate of major postoperative complications after PE with respect to vaginectomy (
p
= 0.027) was recorded. Among them, three women required reoperation within 30 postoperative days, and four experienced two or more complications. Twenty-five (55.6%) women experienced recurrence: 8 of 25 (32.0%) in the vaginectomy group, and 17 of 25 (68%) in the PE group, with a median progression-free survival of 20 months and 13 months, respectively (
p
= 0.169). In total, 5 of 15 (33.3%) died of disease in the vaginectomy group and 13/30 (43.3%) in the PE group, with a median overall survival of 39 and 18 months for vaginectomy and PE, respectively (
p
= 0.161).
Conclusions
The vaginectomy seems to allow for salvage treatment, such as radiotherapy and/or PE, but with a minimal impact on the quality of life in appropriately selected women with local recurrent cervical cancer.
In Reply to Govardhan et al Ferrandina, Gabriella
International journal of radiation oncology, biology, physics,
09/2015, Volume:
93, Issue:
1
Journal Article
MiR-200c and HuR in ovarian cancer Prislei, Silvia; Martinelli, Enrica; Mariani, Marisa ...
BMC cancer,
02/2013, Volume:
13, Issue:
1
Journal Article
Peer reviewed
Open access
MicroRNAs in solid malignancies can behave as predictors of either good or poor outcome. This is the case with members of the miR-200 family, which are the primary regulators of the epithelial to ...mesenchymal transition and have been reported to act as both oncogenes and tumor suppressors. This study assessed the role of miR-200c as regulator of class III β-tubulin (TUBB3), a factor associated with drug-resistance and poor prognosis in ovarian cancer.
Expression of miR-200c was assessed in a panel of ovarian cancer cell lines with inherent or acquired drug-resistance. Stable overexpression of miR-200c was obtained in A2780 and Hey cell lines. Crosslinking-coupled affinity purification method and ribonucleic-immunoprecipitation assay were used to characterise the complexes between miR-200c, HuR and 3'UTR region of TUBB3 mRNA. Nanofluidic technology and immunohistochemistry were used to analyze the expression of HuR, TUBB3 and miR-200c in 220 ovarian cancer patients.
In a panel of ovarian adenocarcinoma cell lines, we observed a direct correlation between miR-200c expression and chemoresistance. In A2780 cells miR-200c targeted TUBB3 3'UTR, while a positive correlation was observed between miR-200c and TUBB3 expression in most of the other cell lines. Through the analysis of 3'UTR-associated complexes, we found that the miR-200c can increase the association of the RNA binding protein HuR with TUBB3 mRNA, whereas HuR binding enhanced TUBB3 mRNA translation. Most importantly, in our analysis on 220 ovarian cancer patients we observed that overexpression of miR-200c correlated with poor or good outcome depending on the cellular localization of HuR.
This study suggests a model for the combined regulatory activity of miR-200c and HuR on TUBB3 expression in ovarian cancer. When HuR is nuclear, high expression of miR-200c inhibits TUBB3 expression and results in a good prognosis, whereas when HuR occurs in cytoplasm, the same miRNA enhances TUBB3 expression and produces a poor outcome. These findings reveal the usefulness of multidimensional analysis in the investigation of the prognostic role of miRNA expression.
We investigate the prognostic role of pre-treatment ratio between Type 1 (M1) and Type 2 (M2) tumor-associated macrophages (TAMs) in locally advanced cervical cancer (LACC) patients treated with ...chemoradiation (CT/RT).
84 consecutive LACC patients treated with cisplatin-based CT/RT for a total dose of 50.0 Gy, followed by radical surgery were analysed. Double-staining immunohistochemistry of CD163/p-STAT, CD68/pSTAT1, CD163/c-MAF, and CD68/c-MAF was performed on tumor samples taken at the time of diagnosis. TAMs with CD163+pSTAT1+, or CD68+pSTAT1+ were defined M1; CD163+c-MAF+ or CD68+c-MAF+ defined the M2 phenotype. The number of M1 and M2 cells was counted at low magnification by evaluating for each case the same tumour area. The ratio between M1 and M2 (M1/M2) was finally calculated.
At diagnosis, we observed a direct correlation between the number of circulating monocytes and of TAMs (p-value = 0.001). Patients with high M1/M2 experienced more frequently complete pathologic response (no residual tumor) to CT/RT, compared to cases with low M1/M2 (55.0% Vs 29.5%; p-value = 0.029). At multivariate analysis M1/M2 (OR = 2.067; p-value = 0.037) emerged as independent predictor of pathologic response to CT/RT. Women with high M1/M2 showed a longer 5-yrs Disease-free (67.2% Vs. 44.3%; p-value = 0.019), and 5-yrs Overall (69.3% Vs. 46.9%; p-value = 0.037) survival, compared to cases with low M1/M2. The presence of a high M1/M2 ratio was independently associated with an unfavourable survival outcome in multivariate analysis.
Polarisation of TAMs toward a M2 phenotype, as reflected by a lower M1/M2 ratio, is an independent predictor of poor response to CT/RT, and shorter survival in LACC.
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