Dose-dense neoadjuvant chemotherapy before radical surgery in cervical cancer: a retrospective cohort study and systematic literature review.

OBJECTIVE: To evaluate the role of dose-dense neoadjuvant chemotherapy followed by radical hysterectomy in reducing adjuvant radiotherapy in International Federation of Gynecology and Obstetrics (FIGO) 2018 stage IB1-IB2/IIA1 cervical cancer with disrupted stromal ring and as an alternative to concurrent chemoradiotherapy in FIGO 2018 stages IB3/IIA2. METHODS: This was a retrospective cohort study including patients with FIGO 2018 stage IB1-IIA2 cervical cancer undergoing dose-dense neoadjuvant chemotherapy at the European Institute of Oncology in Milan, Italy between July 2014 and December 2022. Weekly carboplatin (AUC2 or AUC2.7) plus paclitaxel (80 or 60 mg/m2, respectively) was administered for six to nine cycles. Radiological response was assessed by Response Evaluation Criteria in Solid Tumours (RECIST) v1.1 criteria. The optimal pathological response was defined as residual tumor ≤3 mm. Kaplan-Meier curves were used to estimate survival rates. A systematic literature review on dose-dense neoadjuvant chemotherapy before surgery for cervical cancer was also performed. RESULTS: A total of 63 patients with a median age of 42.8 years (IQR 35.3-47.9) were included: 39.7% stage IB-IB2/IIA1 and 60.3% stage IB3/IIA2. The radiological response was as follows: 81% objective response rate (17.5% complete and 63.5% partial), 17.5% stable disease, and 1.6% progressive disease. The operability rate was 92.1%. The optimal pathological response rate was 27.6%. Adjuvant radiotherapy was administered in 25.8% of cases. The median follow-up for patients who underwent radical hysterectomy was 49.7 months (IQR 16.8-67.7). The 5-year progression-free survival and overall survival were 79% (95% CI 0.63 to 0.88) and 92% (95% CI 0.80 to 0.97), respectively. Fifteen studies including 697 patients met the eligibility criteria for the systematic review. The objective response rate, operability rate, and adjuvant radiotherapy rate across studies ranged between 52.6% and 100%, 64% and 100%, and 4% and 70.6%, respectively. CONCLUSIONS: Dose-dense neoadjuvant chemotherapy before radical surgery could be a valid strategy to avoid radiotherapy in stage IB1-IIA2 cervical cancer, especially in young patients desiring to preserve overall quality of life. Prospective research is warranted to provide robust, high-quality evidence.

Malignant Mixed Müllerian Tumour of the Uterus: Analysis of 44 Cases.

OBJECTIVES: The aim of our study was to evaluate the clinicopathological features and prognostic factors of uterine carcinosarcoma. PATIENTS AND METHODS: In this retrospective study, the clinical characteristics of 44 patients with uterine MMMT were evaluated. Survival curves were estimated by the Kaplan-Meier method and compared by the log-rank test. RESULTS: Forty-four patients with uterine carcinosarcoma were referred to our unit between 1995 and 2015. Their median age was 66.5 years. All women underwent total abdominal hysterectomy and bilateral salpingo-oophorectomy. Twenty-five percent had omental resection. Pelvic lymphadenectomy was performed in 18.2% of the cases. Twenty-six of the patients presented with stage I/II disease, 17 with advanced stages. In 20.5% of the cases there were metastases at diagnosis. Forty women received adjuvant chemotherapy, with complete remission in 67.9% of the cases. Recurrences were observed in 27.3% of the women. Disease-free and overall survival was 27 and 103 months, respectively. The FIGO stage, histological type, tumour size, chemotherapy regimen, pelvic lymphadenectomy, and myometrial invasion did not affect survival. CONCLUSIONS: Uterine MMMT is an aggressive tumour, often diagnosed at an advanced stage and with a high rate of metastases or recurrences. Because of its rarity, its management is controversial and fixed prognostic factors cannot be defined.

A phase II study: dose-dense carboplatin and paclitaxel as neoadjuvant chemotherapy in locally advanced cervical cancer.

This study evaluates the efficacy and toxicity of dose-dense weekly paclitaxel and carboplatin as neoadjuvant chemotherapy in locally advanced cervical cancer (LACC). We collected 23 cases of LACC treated with weekly paclitaxel and carboplatin for nine cycles: 20 patients had complete or partial response to chemotherapy and were submitted to surgery, 3 with poor response received chemoradiation therapy. Pathologic examination showed complete response in four patients, myometrial invasion <50% in nine and >50% in seven patients, parametrial involvement in two, vaginal metastasis in one and lymphovascular space invasion, with positive margins, in another case. Despite seven patients had radiological evidence of lymph nodes involvement at diagnosis, only one had nodal metastases. Five patients showed grade 3-4 of hematologic toxicity.

BRCAmut and "founder effect": a prospective study in a single academic institution.

INTRODUCTION: About 25% of ovarian cancers can be classified as hereditary. Of these, 80-90% are correleted with the Hereditary Breast-Ovarian Cancer Syndrome (HBOC), which is linked to BRCA 1/2 genes mutations. Our study was set up to study the BRCA-mutation incidence in Apulian population affected with ovarian cancer and to understand the characteristics of the ovarian disease BRCAmut-related. RESULTS: One hundred and five Apulian patients affected by ovarian cancer with serous high grade histotype, were collected. Of these, 39% were carriers of BRCA 1/2 mutation. BRCAmut patients present a lower median age of onset, a lower percentage of neoplasms in advanced stages and a lower mortality than wild type patients; BRCA-mutated patients have longer mean values of Progression Free Survival (PFS) and Overall Survival (OS). CONCLUSIONS: Apulia is a geographical area with a significant BRCA-mutation incidence variation in the population affected by ovarian cancer. BRCAmut-related ovarian disease is characterized by an earlier median age of onset, an earlier diagnosis and a better outcome than the sporadic disease. MATERIALS AND METHODS: From July 2015 to October 2017, all ovarian cancer patients with serous high grade histotype referred to our Institution were prospectly collected. A BRCA-mutation genetic testing after counselling was offered to all of these patients. Clinical characteristics of all ovarian cancer patients were evaluated. Survival curves were estimated by Kaplan-Meier method and compared with log-rank test.

A retrospective evaluation of the association of celiac disease and growth hormone deficiency: more than a casual association?

BACKGROUND: A transient dysfunction of the endocrine growth axis has been reported in celiac disease (CD). This apparent growth hormone deficiency (GHD) generally normalizes with the institution of a gluten-free diet (GFD). However, in few cases, the dysfunction of the GH axis persists despite a good adherence to the GFD. Aims of this study were to investigate pediatric patients with concurrent CD and GHD and to compare them with patients with isolated CD. METHODS: Data regarding CD patients with and without associated GHD were retrospectively collected. Inclusion criteria were availability of anthropometric and laboratory data at baseline and regularly at the reference center up to a 2-year follow-up. In case of poor catch-up growth despite a good adherence to the GFD, endocrinological investigation was carried on. RESULTS: Fifty-three patients with CD were included. Four (7.5%) out of 53 CD patients had a concurrent GHD. In two cases, firstly diagnosed with CD, GHD was suspected because of a poor catch-up growth despite a good adherence to the GFD. In two other cases, firstly diagnosed with GHD, gastrointestinal symptoms revealed the diagnosis of CD. Normalization of height velocity was achieved by GH treatment in all cases. No statistical significant difference between the two groups of patients was found as regard laboratory and histological features of CD. It is to note that 2 out of 4 patients with concomitant CD and GHD had thyroiditis compared to 6% of patients with isolated CD (P=0.004). CONCLUSIONS: A high prevalence of CD and GHD association was found. CD patients with poor catch-up growth despite a good adherence to the GFD should be carefully investigated for endocrine disorders.