The prognostic value of FIGO staging defined by combining MRI and [18F]FDG PET/CT in patients with locally advanced cervical cancer.

The last version of the FIGO classification recommended imaging tools to complete the clinical assessment of patients with cervical cancer. However, the preferable imaging approach is still unclear. We aimed to explore the prognostic power of Magnetic Resonance Imaging (MRI), contrast-enhanced Computed Tomography (ceCT), and [18F]-Fluorodeoxyglucose Positron Emission Tomography ([18F]FDG-PET)/CT in patients staged for locally advanced cervical cancer (LACC, FIGO stages IB3-IVA). Thirty-six LACC patients (mean age 55.47 ± 14.01, range 31-82) were retrospectively enrolled. All of them underwent MRI, ceCT and [18F]FDG-PET/CT before receiving concurrent chemoradiotherapy. A median dose of 45 Gy (range 42-50.4; 25-28 fractions, 5 fractions per week, 1 per day) was delivered through the external-beam radiation therapy (EBRT) on the pelvic area, while a median dose of 57.5 Gy (range 16-61.1; 25-28 fractions, 5 fractions per week, 1 per day) was administered on metastatic nodes. The median doses for brachytherapy treatment were 28 Gy (range 28-30; 4-5 fractions, 1 every other day). Six cycles of cisplatin or carboplatin were administered weekly. The study endpoints were recurrence-free survival (RFS) and overall survival (OS). Metastatic pelvic lymph nodes at MRI independently predicted RFS (HR 13.271, 95% CI 1.730-101.805; P = 0.027), while metastatic paraaortic lymph nodes at [18F]FDG-PET/CT independently predicted both RFS (HR 11.734, 95% CI 3.200-43.026; P = .005) and OS (HR 13.799, 95% CI 3.378-56.361; P < 0.001). MRI and [18F]FDG-PET/CT findings were incorporated with clinical evidences into the FIGO classification. With respect to the combination of clinical, MRI and ceCT data, the use of next-generation imaging (NGI) determined a stage migration in 10/36 (27.7%) of patients. Different NGI-based FIGO classes showed remarkably different median RFS (stage IIB: not reached; stage IIIC1: 44 months; stage IIIC2: 3 months; P < 0.001) and OS (stage IIB: not reached; stage IIIC1: not reached; stage IIIC2: 14 months; P < 0.001). A FIGO classification based on the combination of MRI and [18F]FDG-PET/CT might predict RFS and OS of LACC patients treated with concurrent chemoradiotherapy.

Oligometastatic Prostate Cancer Treated with Metastasis-Directed Therapy Guided by Positron Emission Tomography: Does the Tracer Matter?

The superior diagnostic accuracy of [68Ga]Ga-prostate-specific membrane antigen-11 (PSMA) ([68Ga]Ga-PSMA-11) compared to [18F]F-Fluorocholine Positron Emission Tomography/Computed Tomography (PET/CT) in Prostate Cancer (PCa) is established. However, it is currently unclear if the added diagnostic accuracy actually translates into improved clinical outcomes in oligometastatic PCa patients treated with [68Ga]Ga-PSMA-11 PET-guided metastasis-directed therapy (MDT). The present study aimed to assess the impact of these two imaging techniques on Progression-Free Survival (PFS) in a real-world sample of oligometastatic PCa patients submitted to PET-guided MDT. Thirty-seven oligometastatic PCa patients treated with PET-guided MDT were retrospectively enrolled. MDT was guided by [18F]F-Fluorocholine PET/CT in eleven patients and by [68Ga]Ga-PSMA-11 PET/CT in twenty-six. Progression was defined as biochemical recurrence (BR), radiological progression at subsequent PET/CT imaging, clinical progression, androgen deprivation therapy initiation, or death. Clinical and imaging parameters were assessed as predictors of PFS. [18F]F-Fluorocholine PET-guided MDT was associated with significantly lower PFS compared to the [68Ga]Ga-PSMA-11 group (median PFS, mPFS 15.47 months, 95% CI: 4.13−38.00 vs. 40.93 months, 95% CI: 40.93−40.93, respectively; p < 0.05). Coherently, the radiotracer used for PET-guided MDT resulted in predictive PFS at the univariate analysis, as well as the castration-resistant status at the time of MDT and the PSA nadir after MDT. However, in the multivariate analysis, castration resistance and PSA nadir after MDT remained the sole independent predictors of PFS. In conclusion, in the present proof-of-concept study, [68Ga]Ga-PSMA-11 provided higher PFS rates than [18F]F-Fluorocholine imaging in oligometastatic PCa patients receiving PET-guided MDT. Although preliminary, this finding suggests that enlarging the "tip of the iceberg", by detecting a major proportion of the submerged disease thanks to next-generation imaging may favourably impact the oncological outcome of oligometastatic PCa treated with MDT.

Management of ASC-US/HPV positive post-menopausal woman.

BACKGROUND: The aim of our study was to determine which diagnostic course is best to identify women at risk of CIN2+ among post-menopausal women with cytological diagnosis of ASCUS METHODS: We selected women who had been post-menopausal for at least one year , and who had completed the entire diagnostic-therapeutic course that they had undertaken. The sample was divided into two arms: in the first arm, we considered 146 ASCUS positive women who had undergone the HPV test, colposcopy and then underwent more detailed diagnostics by means of LEEP or a scraping of the cervical canal. The second arm was made up of 124 ASCUS positive women who had undergone a vaginal administration of estriolo, the HPV test and colposcopy. Estriol was administered for 5 weeks: the first week one vaginal suppository every evening, the other four weeks the administration was twice a week. Then, the patients underwent colposcopy. In cases of positivity a biopsy was carried out, the patients positive for CIN2+ at the biopsy underwent excisional therapy using LEEP and were followed up. The patients, who were negative at colposcopy or with histological diagnosis of CIN1, were examined again at 1 year. RESULTS: In the first arm the HPV test had an SE of 94%, an SP of 68%, NPV of 99%, and PPV of 28%. The PPV is very low because of the elevated percentage of false positives that the HPV test gave (71%). In the second arm the HPV test maintained its high SE (100%), an SP of 74%, a NPV of 100%, and a PPV of 43%. The use of estrogen increased the specificity of the test. CONCLUSION: It is important to say that the second arm indicates the use of local estrogen therapy only for ASCUS/HPV positive postmenopausal women. Therefore, the HPV test should be used as the first diagnostic possibility in cases of ASCUS in post-menopausal women, associating local estrogen therapy only with HPV positive women.

HPV genotype determination and E6/E7 mRNA detection for management of HPV positive women.

BACKGROUND: Clinical management of HPV positive women is difficult since many of the infections, including high-risk oncogene genotypes (hr-HPV), are transient. Therefore only a limited number of patients have a high-grade lesion and sending all HPV positive women for colposcopy would only increase costs and unnecessary treatment, with serious psychological consequences for patients. The need has emerged to identify other HPV related markers able to correctly detect women with a high-risk of developing high-grade lesions. Genotyping and the search for E6/E7 mRNA are among the possible candidates. METHODS: The study was carried out by means of an observational analysis of the data relative to 674 HR-HPV positive women who we had observed from January 2013 to June 2015; the data had been gathered in a database at the HPV Center of the University Hospital of Catania, Italy. Women were considered eligible for this study if the following data was present in the database: Pap TEST, histologic evaluation, HPV TEST and E6/E7 mRNA detection. We calculated the Odds Ratio (OR) of woman who were mRNA positive, with CIN2+ lesions, and Odds Ratio of HPV16 positive women. RESULTS: Transcripts were detected in 23.6% (69/292) of the women with CIN1 and in 97.2% (210/220) of those with CIN2 + . Regarding genotyping, the 81,8% (180/220) of the women with CIN2+ had genotype 16, while only 18.1% (40/220) had genotype 18, 31, 33, 45. We calculated the OR in the group of HPV16 women with CIN2+ (OR = 4.62; 95% CI = 3.13 to 6.82), this value increased (OR = 106.12; 95% CI = 53.71 to 209.69) in women with CIN2+ and positive mRNA. DISCUSSION: The presence of the HPV16 genotype in our study was associated with a risk 5 times greater of developing a high-grade lesion (CIN2+) (OR = 4.62 95% CI:3.13-6.82); this supports the hypothesis that it would be opportune to have targeted protocols for the management of HPV 16 positive women. The results showed that there was an association between E6/E7 mRNA expression and histology (OR = 106.12; 95% CI = 53.71 to 209.69). The E6/E7 mRNA test showed a higher prevalence of E6 and E7 transcripts in patients with higher-grade lesions. CONCLUSION: The results of this study suggest that the HPV genotype determination and E6/E7 mRNA detection would find an important application for management of HPV positive women.