Local experience in cervical cancer imaging: Comparison in tumour assessment between TRUS and MRI.

OBJECTIVE: The aim of study was to analyze the accuracy of TRUS (transrectal ultrasound) vs. MRI (magnetic resonance imaging) and clinical gynecological examination estimation in the evaluation of tumor dimensions. METHODS: The patients inclusion criterion included primarily pathologically squamous cell carcinoma, but excluded were patients who had not undergone BT (brachytherapy) and treated with palliative intent. We offer two types of treatment for locally advanced cervical cancer: (a) radiochemotherapy followed by surgery and (b) exclusive radiochemotherapy. Imaging tests follow the presence of tumor and tumor size (width and thickness). Each examination was performed by a different physician who had no knowledge of the others' findings. All patients underwent MRI prior to EBRT (external beam radiation therapy) while 18 of them also at the time of the first brachytherapy application. For the analysis we used the r-Pearson correlation coefficient. RESULTS: In 2013, 26 patients with cervical cancer were included. A total of 44 gynecological examinations were performed, 44 MRIs and 18 TRUSs. For the comparisons prior to EBRT the correlation coefficient between TRUS vs. MRI was r = 0.79 for AP and r = 0.83 for LL, for GYN vs. MRI was r = 0.6 for AP and r = 0.75 for LL. Prior to BT for GYN vs. MRI, r values were 0.60 and 0.63 for AP and LL, respectively; for GYN vs. TRUS, r values were 0.56 and 0.78 for AP and LL, respectively. CONCLUSIONS: A high correlation between the three examinations was obtained. As such, TRUS can be considered a suitable method in the evaluation of tumor dimensions.

Gene expression profiling reveals activation of the FA/BRCA pathway in advanced squamous cervical cancer with intrinsic resistance and therapy failure.

BACKGROUND: Advanced squamous cervical cancer, one of the most commonly diagnosed cancers in women, still remains a major problem in oncology due to treatment failure and distant metastasis. Antitumor therapy failure is due to both intrinsic and acquired resistance; intrinsic resistance is often decisive for treatment response. In this study, we investigated the specific pathways and molecules responsible for baseline therapy failure in locally advanced squamous cervical cancer. METHODS: Twenty-one patients with locally advanced squamous cell carcinoma were enrolled in this study. Primary biopsies harvested prior to therapy were analyzed for whole human gene expression (Agilent) based on the patient's 6 months clinical response. Ingenuity Pathway Analysis was used to investigate the altered molecular function and canonical pathways between the responding and non-responding patients. The microarray results were validated by qRT-PCR and immunohistochemistry. An additional set of 24 formalin-fixed paraffin-embedded cervical cancer samples was used for independent validation of the proteins of interest. RESULTS: A 2859-gene signature was identified to distinguish between responder and non-responder patients. 'DNA Replication, Recombination and Repair' represented one of the most important mechanisms activated in non-responsive cervical tumors, and the 'Role of BRCA1 in DNA Damage Response' was predicted to be the most significantly altered canonical pathway involved in intrinsic resistance (p = 1.86E-04, ratio = 0.262). Immunohistological staining confirmed increased expression of BRCA1, BRIP1, FANCD2 and RAD51 in non-responsive compared with responsive advanced squamous cervical cancer, both in the initial set of 21 cervical cancer samples and the second set of 24 samples. CONCLUSIONS: Our findings suggest that FA/BRCA pathway plays an important role in treatment failure in advanced cervical cancer. The assessment of FANCD2, RAD51, BRCA1 and BRIP1 nuclear proteins could provide important information about the patients at risk for treatment failure.

CT Angiography-Guided Needle Insertion for Interstitial Brachytherapy in Locally Advanced Cervical Cancer.

CT angiography might be a suitable procedure to avoid arterial puncture in combined intracavitary and interstitial brachytherapy for cervical cancer curatively treated with combined chemoradiation and brachytherapy boost. Data in the literature about this technique are scarce. We introduced this method and collected brachytherapy data from patients treated in our department between May 2021 and April 2024. We analyzed the applicator subtype, needle insertion (planned versus implanted), implanted depth and the role of CT angiography in selecting needle trajectories and insertion depths. None of the patients managed through this protocol experienced atrial puncture and consequent hemorrhage. Needle positions were accurately selected with the aid of CT angiography with proper coverage of brachytherapy targets and avoidance of organs at risk. CT angiography is a promising method for guiding needle insertion during interstitial brachytherapy.

Randomized phase 3 trial comparing 2 cisplatin dose schedules in 326 patients with locally advanced squamous cell cervical carcinoma: long-term follow-up.

OBJECTIVE: The evaluation of 5-year results obtained through 2 radiochemotherapy (RCT) regimens: cisplatin (CDDP), 20 mg/m × 5 days every 21 days; and CDDP, 40 mg/m per week in locally advanced cervical carcinoma. METHODS/MATERIALS: In this single-institution prospective randomized phase 3 study, 326 patients with stage IIB to IIIB squamous cell cervical carcinoma treated from March 2003 to March 2005 were included. One hundred sixty patients (49%) had stage IIB cervical carcinoma, 103 patients (31.5%) had stage IIIA cervical carcinoma, and 63 patients (19.5%) had stage IIIB cervical carcinoma. The patients were randomly assigned to 2 therapeutic arms: 164 patients in arm A (5 days) concurrent RCT with CDDP, 20 mg/m per day, days 1 to 5 every 21 days; and 162 patients in arm B (weekly), concurrent RCT with CDDP, 40 mg/m per day weekly. All patients were treated with external beam radiotherapy on the abdominopelvic region using 15-MV x-rays and a cervical boost using the x-rays arch technique or medium-dose-rate intracavitary brachytherapy. RESULTS: The 5-year survival rate obtained through the 2 RCT regimens are not statistically different, even if a tendency of superiority can be observed in the 5-day arm as far as overall survival (78% in arm A vs 72% in arm B; p = 0.14) and disease-free survival (73% in arm A and 69% in arm B; p = 0.09) are concerned. Five-year local relapse-free survival was significantly superior in the 5-day CDDP arm (87%) in comparison with the weekly CDDP arm (77%); p < 0.01. In the 5-day arm, local relapse rate was twice lower, 21/164 (13%), compared with the weekly arm, 40/162 (25%); p < 0.01). Distance failures were identical in the 2 therapeutic groups: 22/164 (13%) and 21/162 (13%), respectively, which shows the superiority of arm A regarding local control. CONCLUSIONS: The results of our study demonstrate that RCT with cisplatin, 20 mg/m × 5 days every 21 days, is superior regarding local efficacy and is less toxic compared with the weekly chemotherapy regimen.

Role of Brachytherapy in the Postoperative Management of Endometrial Cancer: Decision-Making Analysis among Experienced European Radiation Oncologists.

BACKGROUND: There are various society-specific guidelines addressing adjuvant brachytherapy (BT) after surgery for endometrial cancer (EC). However, these recommendations are not uniform. Against this background, clinicians need to make decisions despite gaps between best scientific evidence and clinical practice. We explored factors influencing decision-making for adjuvant BT in clinical routine among experienced European radiation oncologists in the field of gynaecological radiotherapy (RT). We also investigated the dose and technique of BT. METHODS: Nineteen European experts for gynaecological BT selected by the Groupe Européen de Curiethérapie and the European Society for Radiotherapy & Oncology provided their decision criteria and technique for postoperative RT in EC. The decision criteria were captured and converted into decision trees, and consensus and dissent were evaluated based on the objective consensus methodology. RESULTS: The decision criteria used by the experts were tumour extension, grading, nodal status, lymphovascular invasion, and cervical stroma/vaginal invasion (yes/no). No expert recommended adjuvant BT for pT1a G1-2 EC without substantial LVSI. Eighty-four percent of experts recommended BT for pT1a G3 EC without substantial LVSI. Up to 74% of experts used adjuvant BT for pT1b LVSI-negative and pT2 G1-2 LVSI-negative disease. For 74-84% of experts, EBRT + BT was the treatment of choice for nodal-positive pT2 disease and for pT3 EC with cervical/vaginal invasion. For all other tumour stages, there was no clear consensus for adjuvant treatment. Four experts already used molecular markers for decision-making. Sixty-five percent of experts recommended fractionation regimens of 3 × 7 Gy or 4 × 5 Gy for BT as monotherapy and 2 × 5 Gy for combination with EBRT. The most commonly used applicator for BT was a vaginal cylinder; 82% recommended image-guided BT. CONCLUSIONS: There was a clear trend towards adjuvant BT for stage IA G3, stage IB, and stage II G1-2 LVSI-negative EC. Likewise, there was a non-uniform pattern for BT dose prescription but a clear trend towards 3D image-based BT. Finally, molecular characteristics were already used in daily decision-making by some experts under the pretext that upcoming trials will bring more clarity to this topic.

Radiotherapy versus concurrent 5-day cisplatin and radiotherapy in locally advanced cervical carcinoma. Long-term results of a phase III randomized trial.

PURPOSE: To prove the superiority of concurrent radiochemotherapy (RTCT) over radiotherapy (RT) alone in locally advanced cervical carcinoma. PATIENTS AND METHODS: In this randomized monocentric phase III study, 566 patients with squamous cell carcinoma of the cervix were included: 284 in arm A (RT) and 282 in arm B (concurrent RTCT with cisplatin 20 mg/m(2) x 5 days). 238 patients (42%) were in stage IIB, 209 (37%) in stage IIIA, and 119 (21%) in stage IIIB. The median follow-up was 62.8 months. RT to the pelvis was delivered to a dose of 46 Gy/23 fractions. A cervical boost was given using the X-ray arch technique or high-dose-rate intracavitary brachytherapy at a dose of 10 Gy. Thereafter, patients were evaluated: those with good response optionally underwent surgery and the others continued RT until 64 Gy/pelvis (with or without CT according to randomization) and 14 Gy/central tumor volume. RESULTS: The 5-year survival rate was statistically significantly superior in the concurrent RTCT group (74%) versus the RT group (64%; p < 0.05). In patients undergoing surgery after RT or RTCT, superior results were obtained, compared to the nonoperated patients: 5-year survival rate 86% versus 53% (p < 0.01). 192 failures were recorded: 109 (38%) after RT alone versus 83 (29%) after concurrent RTCT (p < 0.01). CONCLUSION: The results of this study prove the obvious superiority of concurrent RTCT with 5-day cisplatin compared to RT alone in patients with locally advanced cervical carcinoma, regarding local control (78% vs. 67%) and 5-year survival rates (74% vs. 64%).

Long-term survival following neoadjuvant chemotherapy and concomitant radiochemotherapy in locally advanced cervical cancer: results of the Oncology Institute "Prof. Dr. Ion Chiricuta" experience.

Objective:to analyze the efficiency of (NACT) followed by concurrent radiochemotherapy (RCT) in patients with locally advanced cervical cancer, 5-year overall, specific and disease-free survival and the prognostic factors correlated with the response and survival. Materials and methods:207 patients with cervical carcinoma stages IIB-IIIB, who received 2-4 cycles of neoadjuvant chemotherapy followed by concurrent chemoradiation were retrospectively analyzed for an objective response (OR), overall survival (OS), and disease-specific survival (DSS) rate. All patients received platinum-based NACT followed by concurrent RCT to a total dose (TD) of 46 Gy/pelvis when patients were evaluated for surgery. Patients with favorable parametrial response optionally underwent surgery. The rest of the patients continued radiochemotherapy exclusively. Results:The baseline characteristics were: median age at diagnosis - 52 years; 82% squamous and 12% adenocarcinoma histologies; 67 patients (32.4%) with FIGO stage IIB, 87 (42%) with stage IIIA and 53 (25.6%) with stage IIIB. The OR rate was 56.5% post-NACT and the complete response (CR) after exclusive RCT was 19.7% while pathological complete response (pCR) in patients that underwent surgery was 61.2%. The median follow-up was 58.3 months. Overall and disease-specific survivals at 5 years were 78% and 84%, respectively. The OS for stages IIB and IIIA was 84%, and 61% for stage IIIB while the DSS rates were 90% for stage IIB, 86% for stage IIIA and 72% for stage IIIB. The disease-free intervals (DFS) rates were 88%, 76% and 69% for stages IIB, IIIA and IIIB, respectively. Conclusions:Neoadjuvant chemotherapy followed by concurrent chemoradiation produces higher response rates and improvements in disease-specific survival and disease-free survival rates compared to RCT.

Impact of exposure to tobacco smoke, arsenic, and phthalates on locally advanced cervical cancer treatment-preliminary results.

BACKGROUND: Cancer research is a national and international priority, with the efficiency and effectiveness of current anti-tumor therapies being one of the major challenges with which physicians are faced. OBJECTIVE: To assess the impact of exposure to tobacco smoke, arsenic, and phthalates on cervical cancer treatment. METHODS: We investigated 37 patients with locally advanced cervical carcinoma who underwent chemotherapy and radiotherapy. We determined cotinine and five phthalate metabolites in urine samples collected prior to cancer treatment, by gas chromatography coupled to mass spectrometry, and urinary total arsenic by atomic absorption spectrometry with hydride generation. We used linear regression to evaluate the effects of cotinine, arsenic, and phthalates on the change in tumor size after treatment, adjusted for confounding variables. RESULTS: We detected no significant associations between urinary cotinine, arsenic, or phthalate monoesters on change in tumor size after treatment, adjusted for urine creatinine, age, baseline tumor size, and cotinine (for arsenic and phthalates). However, higher %mono-ethylhexyl phthalate (%MEHP), a putative indicator of phthalate diester metabolism, was associated with a larger change in tumor size (ß = 0.015, 95% CI [0.003-0.03], P = 0.019). CONCLUSION: We found no statistically significant association between the urinary levels of arsenic, cotinine, and phthalates metabolites and the response to cervical cancer treatment as measured by the change in tumor size. Still, our results suggested that phthalates metabolism may be associated with response to treatment for locally advanced cervical cancer. However, these observations are preliminary and will require confirmation in a larger, more definitive investigation.

A prospective study of the value of pre- and post-treatment magnetic resonance imaging examinations for advanced cervical cancer.

BACKGROUND AND AIM: Cervical cancer has high incidence and mortality in developing countries. It is the only gynecological malignancy that is clinically staged. Staging at the time of diagnosis is crucial for treatment planning. After radiation therapy, clinical examination is limited because of radiation changes. An imaging method relatively unaffected by radiation changes would be useful for the assessment of therapy results and for management. We sought to demonstrate the value of magnetic resonance imaging (MRI) in the pre- and post-treatment assessment of cervical cancer. METHODS: This was a prospective study, carried out between November 2012 and October 2014 on 18 subjects with advanced-stage cervical cancer diagnosed by colposcopy. The disease stage was determined clinically according to the International Federation of Gynecology and Obstetrics (FIGO) criteria. Only patients with disease stage ≥ IIB or IIA with one of the tumor dimensions > 4 cm were enrolled in the study. All patients underwent abdominal-pelvic contrast-enhanced MRI as part of the workup. Tumor size, local invasion, involved pelvic lymph nodes, and staging according to MRI criteria were evaluated. Clinical and MRI examinations were also performed after chemoradiotherapy. After chemoradiotherapy, 94% of the patients (17 of 18) were treated surgically. RESULTS: Eighteen patients aged 32-67 met the inclusion criteria and were enrolled: 10 stage IIB, 6 stage IIIA, 1 stage IIA and 1 stage IIIB, according to clinical staging. Using histopathological findings as a reference, MRI staging accuracy was 83.3%. The concordance of the clinical stage with MRI stage at the first examination was 56%. Parametrial involvement was assessed on pretreatment and post-treatment MRI, with post-treatment MRI compared with histology. There was no statistically significant difference between the pre- and post-therapy gynecological examinations (GYN) and the corresponding MRI assessments as to tumor size measurements (p>0.05). The post-therapy restoration of the cervical stroma ruled out tumor recurrence. CONCLUSIONS: For a detailed characterization of loco-regional extension, the calculation of tumor volume, and the evaluation of distant metastatic changes, clinical examination is insufficient. Magnetic resonance imaging is helpful aftertherapy.

Multimodal endocavitary ultrasound versus MRI and clinical findings in pre- and post-treatment advanced cervical cancer. Preliminary report.

AIMS: The aim of this study was to evaluate the use of pre and post-therapy transrectal and transvaginal ultrasonography (TRUS, TVUS) with contrast enhancement and strain elastography compared with clinical examination and magnetic resonance imaging (MRI) in the assessment of advanced stage cervical cancer. MATERIAL AND METHODS: This was a prospective study, carried out over a period of nine months on subjects with advanced-stage cervical cancer (stage >/= IIB). All included patients were examined clinically and underwent abdomino-pelvic contrast enhanced MRI and multimodal US examinations (TRUS with strain elastography and contrast enhanced TVUS) at the time of diagnosis and after radiochemotherapy. Tumor size and staging at TRUS and TVUS was compared with the same data obtained by clinical examination and MRI. Pathology was the golden standard. RESULTS: Eight patients accomplished the inclusion criteria. In five cases the tumor stage was identical on clinical and MRI examinations. In all cases parametrial infiltration was diagnosed by all pre-treatment examinations. No significant differences were observed in tumor size between clinical, US and MRI exams either at baseline or post-therapy, in native or post-contrast examinations. The size of the tumor evaluated pre-treatment proved to be significantly smaller post-contrast in both US and MRI examinations compared with the native images. Post-therapy, no significant differences were observed on US measured tumor dimensions when comparing native with post-contrast images. Oppositely, significant smaller dimensions were observed on post-contrast MRI compared with native scans. CONCLUSIONS: TRUS is accurate in the estimation of pre-therapy cervical cancer dimension. The post therapy tumor evaluation is better performed with MRI. The use of intravenous contrast agents on both examinations did not improved the accuracy of tumor evaluation pre or post-therapy.

Expression of VEGF, VEGFR, EGFR, COX-2 and MVD in cervical carcinoma, in relation with the response to radio-chemotherapy.

INTRODUCTION: Despite the improvement in the treatment results due to modern irradiation techniques and to the association of chemo-radiotherapy, cervical cancer remains an unsolved problem of oncology both due to the increased rate of local failures and of the distant metastasis. Efforts to implement new therapeutic strategies in order to obtain better results in patients with cervical cancer appear justified. Neovascularization is an important step in the tumor progression and the therapeutic targeting of the tumor blood vessels appears to be a good strategy to follow in the anti-cancer treatment. Thus, even in an incipient phase of the clinical research process, the combination between the anti-angiogenic aimed therapies and the current radio-chemotherapy seems to represent a new, feasible and promising approach. The aim of the present study was to determine the prognostic and/or predictive value of some biological markers of tumor angiogenesis and of their implication in increasing the efficacy of current treatments for this cancer. MATERIALS AND METHODS: So far, 54 women were included in a prospective trial: 44 having an advanced cervical carcinoma and 10 healthy women, as controls. A tumor biopsy and a blood sample were obtained from each patient before the start of therapy. The density of microvascularization was assessed using CD34 monoclonal antibody (hot spot technique), the expression of angiogenic factors VEGFR, EGFR and COX-2 were determined in tumor biopsies by specific immunohistochemistry techniques, using primary antibodies anti-EGFR, anti-VEGF and anti-COX-2 respectively. The quantitative polymerase chain reaction (Real Time PCR) was employed for assessing the expression level of the genes involved. Serum VEGF was determined by quantitative ELISA technique. RESULTS: Among the studied clinical and molecular factors, we found to be predictive for the type of response the following factors: tumor size at diagnosis (p=0.01), VEGFR2 expression (p=0.02) and a tendency to significance for patients' age (p=0.06). From the large panel of studied markers it was observed correlation between MVD expression with stromal COX-2 (p=0.01) and a tendency with epithelial COX-2 (p=0.06). Stromal COX-2 has higher correlation with VEGFR2 (p=0.01) and MVD (p=0.01) and also has a lower correlation with tumor size (p=0.08). CONCLUSIONS: Univariate analysis demonstrates that the response to radio-chemotherapy in cervical cancer is related to a set of clinical and molecular factors as: the tumor size, the expression of VEGFR2 as mRNA level and the patients' age. Unfortunately, the multivariate analysis by logistic model selects only VEGFR2 expression for prediction of tumor response. The interrelations between the different biomarkers demonstrate the complexity of the tumor progression process and the necessity of further studies to identify new therapeutic targets.