Neoadjuvant chemotherapy prior to radical hysterectomy in locally advanced cervical cancer: a systematic review and meta-analysis.

OBJECTIVE: The objective of this systematic review was to evaluate the effect of different types of neoadjuvant chemotherapy regimens, in terms of optimal pathological response and oncological outcomes, in patients with locally advanced cervical cancer. METHODS: A systematic search of the literature was performed. MEDLINE through PubMed and Embase databases were searched from inception to June 2023. The study was registered in PROSPERO (ID number CRD42023389806). All women with a pathological diagnosis of locally advanced cervical cancer (International Federation of Gynecology and Obstetrics (FIGO) 2009 classification stages IB2-IVA), any age or histology, who underwent intravenous neoadjuvant chemotherapy before radical surgery, and articles only in English language, were included. We conducted a meta-analysis for optimal pathological response after surgery and survival outcomes. The risk of bias was assessed using the Newcastle-Ottawa scale and the Risk of Bias 2 (RoB) tools. The review methods and results were reported according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. RESULTS: 25 studies with a total number of 1984 patients fulfilled the eligibility criteria of our review and were included for data extraction and efficacy analysis. When compared with a two-drug regimen, the three-drug combination including cisplatin, paclitaxel, and ifosfamide or anthracyclines showed superior efficacy in terms of optimal pathological response with an odds ratio of 0.38 (95% CI 0.24 to 0.61, p<0.0001), with no difference in disease-free survival (hazard ratio (HR) 0.72, 95% CI 0.50 to 1.03, I2=0%, p=0.07) and higher overall survival (HR 0.63, 95% CI 0.41 to 0.97, I2=0%, p=0.03). CONCLUSIONS: The three-drug combination of cisplatin, paclitaxel, and ifosfamide or anthracyclines showed a higher rate of complete or optimal partial response, with the triple regimens having an advantage over the platinum-based schedules in terms of overall survival. Neoadjuvant chemotherapy followed by radical surgery should not be considered a standard of care in locally advanced cervical cancer.

Retrospective study of histopathological and prognostic characteristics of primary fallopian tube carcinomas: twenty-year experience (SOCRATE).

OBJECTIVE: Primary fallopian tube carcinoma represents a rare entity, accounting for about 0.75%-1.2% of all gynecological malignancies. The rationale of our study is to describe the prognosis of primary fallopian tube carcinoma. METHODS: We retrospectively identified patients with FIGO stage I-IV, all histology types and grading primary fallopian tube carcinoma treated in three major oncological centers between January 2000 and March 2020. Exclusion criteria were bulky tubo-ovarian carcinomas, isolated serous tubal intraepithelial carcinoma or neoadjuvant chemotherapy. RESULTS: A total of 61 patients were included. The vast majority of primary fallopian tube carcinomas were serous (96.7%) and poorly differentiated (96.7%) and arose from the fimbriated end of the tube (88.5%). Larger tumor size correlated with higher probability of correct preoperative differential diagnosis of primary fallopian tube carcinoma (p=0.003). Up to 82.4% of patients with small tumors (≤15 mm) presented with high FIGO stage (≥IIA). The most common site of metastasis was pelvic peritoneum (18.8%) and among 59% of patients who underwent lymphadenectomy smaller tumors had higher rate of nodal metastasis (42.9%≤10 mm vs 27.3%>50 mm). After 46.0 months of mean follow-up there were 27 recurrences (48.2%). The most common site of relapse was diffuse peritoneal spread (18.5%). The 5-year disease-free survival was 45.2% and 5-year overall survival was 75.5%. Of note, 42.9% of patients with stage IVB survived >36 months. CONCLUSION: Primary fallopian tube carcinoma is a biologically distinct tumor from primary epithelial ovarian carcinoma and it is mostly located in the fimbriated end of the tube. In addition, it is characterized by a high rate of retroperitoneal dissemination even at apparently an early stage and its size does not correlate with FIGO stage at presentation.

Impact of Pregnancy on Breast Cancer Features and Prognosis.

BACKGROUND: pregnancy-associated breast cancer (PABC) affects one in 3000 pregnancies, often presenting with aggressive features. METHODS: We retrospectively evaluated a cohort of 282 young BC patients (≤45 years old) treated between 1995 and 2019, dividing them into three groups: nulliparous women, women with PABC (diagnosed within 2 years since last pregnancy) and women with BC diagnosed > 2 years since last pregnancy. This last group was further stratified according to the time between pregnancy and BC. The analysis encompassed histological factors (tumor size, histotype, grading, nodal involvement, multifocality, lympho-vascular invasion, hormone receptor expression, Ki-67 index, and HER2 expression), type of surgery and recurrence. RESULTS: Age at diagnosis was younger in nulliparous than in parous women (p < 0.001). No significant differences were noticed regarding histological characteristics and recurrences. At univariate analysis, nodal involvement (OR = 2.4; p < 0.0001), high tumor grade (OR = 2.6; p = 0.01), and lympho-vascular invasion (OR = 2.3; p < 0.05), but not pregnancy (OR = 0.8; p = 0.30), influenced DFS negatively. Multivariate analysis confirmed nodal involvement as the only negative independent prognostic factor for a worse DFS (OR = 2.4; p = 0.0001). CONCLUSIONS: in our experience, pregnancy is not an independent adverse prognostic factor for BC DFS.

Where Morphological and Molecular Classifications Meet: The Role of p53 Immunohistochemistry in the Prognosis of Low-Risk Endometrial Carcinoma (GLAMOUR Study).

No prospective study has validated molecular classification to guide adjuvant treatment in endometrial cancer (EC), and not even retrospective data are present for patients with morphological low-risk EC. We conducted a retrospective, multicenter, observational study including 370 patients with low-risk endometrioid EC to evaluate the incidence and prognostic role of p53 abnormal expression (p53abn) in this specific subgroup. Among 370 patients, 18 had abnormal expressions of p53 (4.9%). In 13 out of 370 patients (3.6%), recurrences were observed and two were p53abn. When adjusting for median follow-up time, the odds ratio (OR) for recurrence among those with p53abn versus p53 wild type (p53wt) was 5.23-CI 95% 0.98-27.95, p = 0.053. The most common site of recurrence was the vaginal cuff (46.2%). One recurrence occurred within the first year of follow-up, and the patient exhibited p53abn. Both 1-year and 2-year DFS rates were 94.4% and 100% in the p53abn and p53wt groups, respectively. One patient died from the disease and comprised p53wt. No difference in OS was registered between the two groups; the median OS was 21.9 months (16.4-30.1). Larger multicenter studies are needed to tailor the treatment of low-risk EC patients with p53abn. Performing molecular classification on all EC patients might be cost-effective, and despite the limits of our relatively small sample, p53abn patients seem to be at greater risk of recurrence, especially locally and after two years since diagnosis.

Predicting Response to Anthracyclines in Ovarian Cancer.

(1) Background: Anthracyclines are intriguing drugs, representing one of the cornerstones of both first and subsequent-lines of chemotherapy in ovarian cancer (OC). Their efficacy and mechanisms of action are related to the hot topics of OC clinical research, such as BRCA status and immunotherapy. Prediction of response to anthracyclines is challenging and no markers can predict certain therapeutic success. The current narrative review provides a summary of the clinical and biological mechanisms involved in the response to anthracyclines. (2) Methods: A MEDLINE search of the literature was performed, focusing on papers published in the last two decades. (3) Results and Conclusions: BRCA mutated tumors seem to show a higher response to anthracyclines compared to sporadic tumors and the severity of hand-foot syndrome and mucositis may be a predictive marker of PLD efficacy. CA125 can be a misleading marker of clinical response during treatment with anthracyclines, the response of which also appears to depend on OC histology. Immunochemistry, in particular HER-2 expression, could be of some help in predicting the response to such drugs, and high levels of mutated p53 appear after exposure to anthracyclines and impair their antitumor effect. Finally, organoids from OC are promising for drug testing and prediction of response to chemotherapy.

Neoadjuvant Chemotherapy Prior Fertility-Sparing Surgery in Women with FIGO 2018 Stage IB2 Cervical Cancer: A Systematic Review.

Nowadays, the optimal management of patients with cervical cancers measuring 2-4 cm desiring to maintain fertility is still uncertain. In this systematic review, we assessed the reliability of neoadjuvant chemotherapy (NACT) prior to fertility-sparing (FS) surgery in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB2 cervical cancer, in terms of pathologic response, oncological and obstetric outcomes. The review of the literature was performed following the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Data, using MEDLINE and PubMed, were searched for from 1 January 2005 up to 1 December 2020. We identified 20 articles and 114 women with IB2 disease, possible candidates for NACT prior to FS surgery. However, uterine conservation was achieved only in 76.7% of them. Patients reached optimal pathological response to NACT in 60.9% of cases and a TIP (cisplatin, ifosfamide and paclitaxel) regime was related to the best response. Suboptimal response to NACT appeared to be an independent negative prognostic factor. Up to 9.2% of patients recurred with a median 7.4-months DFS, and 4.6% of patients died of disease. Fifty percent of women tried to conceive after treatment and NACT prior to conization appeared to be the most promising alternative to upfront radical trachelectomy in terms of obstetric outcomes. In conclusion, NACT prior to FS surgery is an option, but the literature about this issue is still weak and FS should be carefully discussed with patients.

Low-Pressure Laparoscopy Using the AirSeal System versus Standard Insufflation in Early-Stage Endometrial Cancer: A Multicenter, Retrospective Study (ARIEL Study).

The aim of our study was to evaluate the benefits of a low-pressure insufflation system (AirSeal) vs. a standard insufflation system in terms of anesthesiologists' parameters and postoperative pain in patients undergoing laparoscopic surgery for early-stage endometrial cancer. This retrospective study involved five tertiary centers and included 152 patients with apparent early-stage disease who underwent laparoscopic surgical staging with either the low-pressure AirSeal system (8−10 mmHg, n = 84) or standard laparoscopic insufflation (10−12 mmHg, n = 68). All the intraoperative anesthesia variables evaluated (systolic blood pressure, end-tidal CO2, peak airway pressure) were significantly lower in the AirSeal group. We recorded a statistically significant difference between the two groups in the median NRS scores for global pain recorded at 4, 8, and 24 h, and for overall shoulder pain after surgery. Significantly more women in the AirSeal group were also discharged on day one compared to the standard group. All such results were confirmed when analyzing the subgroup of women with a BMI >30 kg/m2. In conclusion, according to our preliminary study, low-pressure laparoscopy represents a valid alternative to standard laparoscopy and could facilitate the development of outpatient surgery.

Metastatic Bilateral Strumal Carcinoid: A Case Report and Review of the Literature.

Primary ovarian carcinoids are very rare tumors that belong to the germ cell family of ovarian malignancies. They account for less than 1% of all carcinoid tumors and for less than 0.1% of all ovarian neoplasms. Recurrences are even rarer, with only few cases reported in the literature. Strumal carcinoid has recently been recognized as an extremely rare distinct entity. We report on a patient with bilateral mature cystic teratoma with millimetric foci of ovarian strumal carcinoid who developed lymph node para aortic metastasis after 30 years from primary diagnosis. Our case is thus far the second report of a metastatic strumal carcinoid and the first one in which strumal carcinoid occurred bilaterally and was also metastatic.