Neoadjuvant Chemotherapy Followed by Radical Surgery versus Concurrent Chemo-Radiotherapy in the Treatment of Locally Advanced Cervical Cancer: A Multicenter Retrospective Analysis.

OBJECTIVES: This study aims to evaluate oncological outcomes in women affected by locally advanced cervical cancer (LACC) treated by neoadjuvant chemotherapy before radical surgery (NACT + RS) or concurrent chemo-radiotherapy (CCRT). METHODS: This was a multicenter retrospective analysis of data related to women with LACC (FIGO stage IB2-IVA), who were treated by NACT + RS or CCRT between November 2006 and January 2018. The first endpoints were the evaluation of disease-free survival (DFS) and overall survival (OS); univariate and multivariate analyses were performed for identifying the prognostic factors independently associated with these oncological outcomes. RESULTS: Overall, 106 women were included in the analysis; 55 of them (51.9%) underwent NACT + RS and 51 (48.1%) CCRT, respectively. Patients in the NACT + RS group had a significant better five-year DFS and five-year OS than those in the CCRT group (77.4% vs. 33.4%, p < .001 and 93.8% vs. 56.5%, p = .003). In the multivariate analyses, treatment choice (NACT + RS or CCRT) was the only independent prognostic factor for predicting both DFS (HR = 3.954; 95 CI = 1.898-8.236; p < 0.001) and OS (HR = 5.330; 95 CI = 1.563-18.178; p = 0.008). CONCLUSIONS: This retrospective study demonstrated an improved survival outcome for patients undergoing NACT + RS compared with those undergoing CCRT. Our findings seem to support the use of NACT before RS as an effective alternative option to CCRT standard therapy.

Temporary ovarian suppression during chemotherapy to preserve ovarian function and fertility in breast cancer patients: A GRADE approach for evidence evaluation and recommendations by the Italian Association of Medical Oncology.

The development of premature ovarian failure and subsequent infertility are possible consequences of chemotherapy use in pre-menopausal women with early-stage breast cancer. Among the available strategies for fertility preservation, pharmacological protection of the ovaries using luteinising hormone-releasing hormone analogues (LHRHa) during chemotherapy has the potential to restore ovarian function and fertility after anticancer treatments; however, the possible efficacy and clinical application of this strategy has been highly debated in the last years. Following the availability of new data on this controversial topic, the Panel of the Italian Association of Medical Oncology (AIOM) Clinical Practice Guideline on fertility preservation in cancer patients decided to apply the Grades of Recommendation, Assessment, Development and Evaluation (GRADE) methodology around the relevant and current question on the clinical utility of temporary ovarian suppression with LHRHa during chemotherapy as a strategy to preserve ovarian function and fertility in breast cancer patients. To answer this question, preservation of ovarian function and fertility were judged as critical outcomes for the decision-making. Three possible outcomes of harm were identified: LHRHa-associated toxicities, potential antagonism between concurrent LHRHa and chemotherapy, and lack of the prognostic impact of chemotherapy-induced premature ovarian failure. According to the GRADE evaluation conducted, the result was a strong positive recommendation in favour of using this option to preserve ovarian function and fertility in breast cancer patients. The present manuscript aims to update and summarise the evidence for the use of this strategy in light of the new data published up to January 2016, according to the GRADE process.

Selection of patients with high risk endometrial cancer for surgical staging according to the evaluation of pre- and intraoperative risk factors.

BACKGROUND: The aim of this paper was to assess the accuracy of frozen sections histological examination and preoperative CA-125 to select patients with high risk endometrial cancer. METHODS: We reviewed women with type I endometrial cancer treated from January 2011 through January 2013 at the same university hospital. Preoperative CA-125 and intraoperative frozen sections were analyzed to select patients at high risk for metastases, according to Mayo Clinic algorithm. All patients underwent hysterectomy with bilateral adnexectomy. High risk patients underwent complete surgical staging. Respectively, we compared the accuracy of CA-125, frozen sections, and an algorithm combining Ca-125 plus frozen sections, with permanent sections histology as positive control. χ2 test, Landis and Koch kappa statistics (k), sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and accuracy were determined for each variable. RESULTS: One hundred seventy-two women were included. CA-125 levels, using 8.3 U/ml as cut-off value, showed 63.4% sensitivity, 51.6% specificity, 84.7% PPV, 25.0% NPV, 61.1% accuracy, and a low kappa statistics (k=0.106, P<0.125). Frozen sections demonstrated 97.3% sensitivity, 100% specificity, 100% PPV, 90.0% NPV, 97.8% accuracy and an optimal kappa statistics (k=0.934, P<0.001). The algorithm combining CA-125 with frozen sections showed 99.1% sensitivity, 48.1% specificity, 88.8% PPV, 92.9% NPV, 89.2% accuracy, and a satisfactory kappa statistics (k=0.578, P<0.001). CONCLUSIONS: We proved the utility of Mayo algorithm even in a different institution. Combining CA-125 plus frozen sections doesn't look like advantageous compared to frozen sections alone.

Bevacizumab for the treatment of cervical cancer.

INTRODUCTION: Cervical cancer is still a major cause of morbidity and mortality in women. Early stages and locally advanced cervical cancer are currently treated respectively with surgery and chemoradiation with good prognosis. Persistent, recurrent and metastatic cervical cancers have a poor prognosis. Angiogenesis has been identified as a crucial factor for cervical cancer growth. Recently, research has increasingly focused on the development of targeted therapies, such as anti-angiogenic drugs. Amongst such drugs, bevacizumab, a recombinant humanized monoclonal antibody has been the subject of extensive investigation, including its use in cervical cancer. This was recently approved for the treatment of patients with metastatic, recurrent, or persistent cervical cancer. AREAS COVERED: The aim of this review is to discuss the role of bevacizumab in both locally advanced and metastatic or recurrent cervical cancer and to analyze the studies that have led to the approval of bevacizumab in cervical cancer. EXPERT OPINION: The use of bevacizumab in combination with other chemotherapies in cervical cancer has been proven safe and effective, with a significant improvement in overall survival of patients with advanced cervical cancer. Combination therapy using bevacizumab has been demonstrated to increase toxicity rates but it does not impair patient's quality of life.

The potential of sunitinib as a therapy in ovarian cancer.

INTRODUCTION: Sunitinib malate (SU11248; Sutent®; Pfizer, Inc., New York) is a multi-kinase inhibitor currently approved for use in advanced renal cell carcinoma (RCC), imatinib-resistant/-intolerant gastrointestinal stromal tumours and progressive, well-differentiated pancreatic neuroendocrine tumours in patients with unresectable, locally advanced or metastatic disease. AREAS COVERED: This article describes the mechanism of action and of the pharmacokinetics of sunitinib; further, it summarizes Phase I and II trials on the clinical efficacy, tolerability and safety of this agent in the setting of ovarian cancer (OC) treatment. EXPERT OPINION: On the basis of the current literature, sunitinib has shown modest antitumour activity and acceptable toxicity. Studies investigating the impact of horizontal and vertical combinations should represent a priority of future research. Although clinical Phase II trials on the use of sunitinib in the treatment of OC demonstrated an acceptable profile of AEs, a greater comprehension of the toxicity of this compound is recommended.

Sorafenib for ovarian cancer.

INTRODUCTION: Sorafenib is an unselective inhibitor of multiple kinases which has demonstrated clinical advantage in renal cancer and hepatocellular carcinoma. It inhibits tumor proliferation by targeting receptor accessory factor (Raf) kinase isoforms, inhibiting receptor tyrosine kinases of a variety of pro-angiogenic factors and of several receptor tyrosine kinases involved in neovascularization and tumor development. AREAS COVERED: This review offers an explanation of the mechanism of action and of the pharmacokinetics of sorafenib, and gives readers a complete overview of Phase I and II studies on the clinical efficacy, tolerability and safety of this agent in the setting of ovarian cancer (OC) treatment. EXPERT OPINION: The available results from the studies which investigated the use of sorafenib for OC treatment demonstrated poor clinical benefit either as single agent or in combination therapy. The most promising results have been achieved combining sorafenib with bevacizumab, although overlapping and cumulative toxicities should be taken in consideration. Research should focus its attention to the development of reliable predictive biomarkers to assess response and direct therapy in order to allow patient selection and improving treatment schedules maximizing the clinical benefit and simultaneously minimizing the toxicity related to the chemotherapy. Further studies are needed to evaluate the role of sorafenib in the primary treatment of OC.

Increasing hirsutism due to a granulosa-cell tumor in a woman with polycystic ovary syndrome: case report and review of the literature.

BACKGROUND: Granulosa-cell tumors (GCT), rare malignancies that arise from sex-cord stromal cells, account for less than 5% of ovarian tumors. These tumors present with an endocrine syndrome and mass signs. Surgery is the primary treatment approach. The risk of recurrence is more frequent in the juvenile-onset form. CASE REPORT: We report the case of an obese 18-year-old Caucasian women with hirsutism and oligomenorrhea. Abdominal palpation revealed a voluminous firm mass. Hormonal evaluation documented severe hyperandrogenism. The ovary-specific tumor marker CA125 was elevated, whereas human-chorionic-gonadotropin was in the normal range. Abdominal imaging examination revealed a 19 cm mass in the left ovary. Twenty-four hours after removal of the mass, menstrual flow reappeared and androgens progressively normalized. Microscopically, the predominant pattern was one of uniform, bland, epithelioid to spindle-shaped cells. After three months, a significant weight loss was recorded, hirsutism had decreased slightly and oligomenorrhea reappeared. Δ4-Androstenedione levels remained elevated (4200 ng/L), whereas CA125 had normalized. In light of the pre-existing polycystic-ovary-syndrome (PCOS), the patient started estrogen-progestin treatment. CONCLUSION: We report an interesting case of a woman with severe hirsutism due to GCT, and a history of oligomenorrhea caused by PCOS. After surgery, a dramatic clinical improvement was observed, whereas PCOS signs persisted.

Bevacizumab in endometrial cancer treatment.

INTRODUCTION: There is a critical need to develop effective new strategies for the management of patients with advanced or recurrent endometrial cancer (EC) and molecular targeted therapies; in particular, antiangiogenic drugs represent an interesting field of pharmacological research. One of the most interesting of these agents is bevacizumab, a monoclonal antivascular endothelial growth factor antibody. AREAS COVERED: Mechanism of action and clinical trials of bevacizumab in EC, and suggestions for its future use are reviewed. The most relevant papers and the meeting abstracts published up to December 2011 were used as sources for this review. The purposes of this manuscript are to discuss the rationale of interfering with the process of tumor angiogenesis in EC, to help readers in understanding the mechanism of action of bevacizumab, and to provide a comprehensive summary of initial preclinical and clinical results of this drug in EC patients. EXPERT OPINION: Recent advances in the understanding of the molecular biology of EC have led to development of targeted therapies. Among these, antiangiogenic agents are one of the most promising therapies.

Pharmacokinetic and toxicity considerations for the use of anthracyclines in ovarian cancer treatment.

INTRODUCTION: Safe and effective treatments are needed for ovarian cancer. While there are many drugs currently available, there has recently been a renewed novel interest in the use of anthracyclines. AREAS COVERED: This review summarizes the available evidence on pharmacokinetic (PK) and toxicology implications of anthracyclines and pegylated liposomal doxorubicin (PLD) in the clinical management of women with epithelial ovarian cancer. This article consists of material obtained via Medline, PubMed and EMBASE literature searches, up to September 2010. EXPERT OPINION: PLD is a liposomal formulation of doxorubicin (DXR), with a distinct pharmacokinetic profile, characterized by extended circulation time and a reduced clearance and volume of distribution with respect to the free drug. PLD is effective and well tolerated in relapsed ovarian cancer. The toxicity profile of PLD is characterized by dose-limiting mucosal and cutaneous toxicities, mild myelosuppression and decreased cardiotoxicity compared to free DXR. The good response rate, toxicity profile and pharmacokinetic profile of PLD suggest that PLD could be an option in first-line and second-line treatment in ovarian cancer; especially in those who had experienced taxane-induced toxicity or had a poor performance status.

Spontaneous regression of transplacental metastases from maternal melanoma in a newborn: case report and review of the literature.

We describe a rare case of transplacental-transmitted maternal melanoma to the placenta and foetus during the second pregnancy of a 28-year-old woman. She was aware of a greyish-brown nodular lesion on the right gluteus during her first pregnancy. On histological examination, this lesion resulted to be an amelanocitic melanoma. Breast metastases occurred during her second pregnancy, 18 months after the surgical excision; an emergency Caesarean section performed for the recrudement of her clinical conditions confirmed widespread metastases to the liver, spleen and peritoneum. The patient died 2 weeks after delivery. The newborn, at 3 months of age, presented metastases secondary to maternal melanoma, which were resistant to chemotherapy. The disease regressed spontaneously and the child is now 24 months, alive in complete remission.

Peripartum cardiomyopathy.

According to current definition, peripartum cardiomyopathy (PPCM) is a rare disorder in which left ventricular dysfunction and symptoms of heart failure occur in the last month of pregnancy. It has been reported that the incidence of PPCM is 1 in 3,000-4,000 live births. The pathogenesis is poorly understood, however, infectious, immunologic, and nutritional causes have been hypothesized. Clinical presentation includes usual signs and symptoms of heart failure, and unusual presentations such as thromboembolism. Diagnosis is based upon the clinical presentation of congestive heart failure and the objective evidence of left ventricular systolic dysfunction. Early diagnosis and initiation of treatment are essential to optimize pregnancy outcome. Patients with systolic dysfunction during pregnancy are treated similar to patients who are not pregnant. The mainstays of medical therapy are digoxin, loop diuretics, sodium restriction and afterload reducing agents (hydralazine and nitrates). Due to a high risk for venous and arterial thrombosis, anticoagulation with subcutaneous heparin should be instituted. Angiotensin-converting enzyme inhibitors and angiotensin receptor blockers should be avoided during pregnancy because of severe adverse neonatal effects. Effective treatment reduces mortality rates and increases the number of women who fully recover left ventricular systolic function. The prognosis is poor in patients with persistent cardiomyopathy. Subsequent pregnancies are often associated with recurrence of left ventricular systolic dysfunction.

Breast cancer with synchronous massive metastasis in the uterine cervix: a case report and review of the literature.

INTRODUCTION: Metastatic breast cancer is rare in the female genital tract, and when present it more commonly tends to involve ovary or endometrium; uterine cervix is only occasionally involved. This condition poses differential diagnostic problems in the settings of clinical and pathological investigations. CASE PRESENTATION: An asymptomatic 78-year-old woman came to our attention in the context of routine gynecological surveillance; clinical examination disclosed enlarged uterine body and cervix. Our patient then underwent computed tomography and magnetic resonance imaging that outlined the possibility of cervical cancer with parametrial involvement. Moreover, a suspect mass was found on the mammogram in the left breast. Breast surgical excision was performed, which revealed invasive breast carcinoma, while synchronous cervical biopsy discovered distant metastasis in the uterine cervix. On histological examination, both lesions showed non-cohesive architectural pattern consistent with lobular morphology; anyway, to rule out primary poorly differentiated cervical cancer, appropriate immunohistochemical panel was performed, which confirmed the mammary derivation of the tumor. Due to disseminate disease, the patient underwent multisystemic medical treatment including radiotherapy, chemotherapy and hormone therapy, and she is still alive at 30-month follow-up. DISCUSSION: Genital tract metastases in patients with known breast carcinoma can present with abnormal vaginal bleeding, but they often are asymptomatic. Therefore, only strict gynecological surveillance of these patients can permit early detection of these secondary lesions. Aggressive treatment of isolated cervical metastasis should be performed when feasible; otherwise, systemic chemotherapy with taxane could be sufficient in increasing survival. It should be emphasized that, in most cases, only accurate immunohistochemical investigation, particularly if performed on the primary lesion as well, can solve differential diagnostic problems and allow the clinician to establish appropriate treatment.

Unusual complication of excision of pelvic endometriosis: pseudoaneurysm of the left uterine artery.

We report on a patient who had a pseudoaneurysm arising from the left uterine artery after surgical excision of deep endometriosis. The diagnosis was based on contrast-enhanced multidetector computed tomography angiography. Transfemoral selective catheterization and embolization of the left uterine artery determined a quick improvement of the symptoms.

Feasibility of axillary reverse mapping during sentinel lymph node biopsy in breast cancer patients.

BACKGROUND: This pilot study evaluates the feasibility of axillary reverse mapping (ARM) during sentinel lymph node biopsy (SLNB) in breast cancer patients. METHODS: This study included 72 women with new breast cancer diagnosis, tumor size <2 cm, and clinically negative axilla. At the time of surgery, 2 mL of dermal blue patent were injected intradermally, subcutaneously, and intramuscularly in the ipsilateral upper inner arm in order to map and preserve the lymphatics of the arm. Blue arm lymphatics were preserved when in SLNB field. Microsurgical lymphatic-venous anastomosis (LYMPHA) was performed in women who underwent ALND. RESULTS: In 27 of 72 patients (37.5%), the blue lymphatics draining the arm were observed in the SLNB field. In all these patients, the blue lymphatics were preserved. During ALND, the blue lymphatics draining the arm were visible in 8 out of 9 patients (88.9%); in all these women, the LYMPHA procedure was performed. All ARM blue nodes removed during ALND were negative for malignancy. At 9-month follow-up, no patient had lymphedema. CONCLUSIONS: Arm lymphatic drainage can be observed in the SLNB field in 37.5% of the cases. Using the ARM during SLNB may facilitate the preservation of lymphatics draining the arm.

Evaluation of endometrial thickness in hormone receptor positive early stage breast cancer postmenopausal women switching from adjuvant tamoxifen treatment to anastrozole.

Evaluation of endometrial thickness by transvaginal ultrasonography (TVUS) in postmenopausal estrogen receptor positive breast cancer patients treated with anastrozole after tamoxifen therapy. This study included 70 postmenopausal estrogen receptor positive breast cancer patients who switched to anastrozole after tamoxifen; patients had endometrial thickness >4mm and no endometrial malignancy. Endometrial thickness was measured after anastrozole treatment. Endometrial thickness during anastrozole therapy was lower than after tamoxifen therapy (p<0.001); the mean reduction in endometrial thickness was 4.5mm (+/-3.0). Cystic endometrial appearance was more frequent in patients under tamoxifen than in those under anastrozole (p<0.001). Duration of tamoxifen therapy was not correlated to the endometrial thickness at the time of its suspension. Duration of tamoxifen therapy and endometrial thickness at the time of tamoxifen suspension was correlated to the relative reduction of endometrial thickness during anastrozole therapy. Anastrozole reverses tamoxifen-induced increased endometrial thickness and sonographic endometrial cystic appearance.

Vaginal versus transabdominal hysterectomy: is mode of hysterectomy to influence pelvic statics or is pelvic statics to influence mode of hysterectomy?

BACKGROUND: To check the hypothesis that the mobility of the urethrovesical junction in the preoperative phase is different in women that will undergo either vaginal, abdominal, or laparoscopic-assisted vaginal hysterectomy. METHODS: Eighty-seven consecutive hysterectomies, carried out between January 1999 and December 2001 in our Department, were retrospectively considered. The type of surgical procedure as well as the approach was decided by the surgeon, according to personal experience. Each patient underwent a preoperative transperineal ultrasound, measuring urethral mobility. The ultrasounds were repeated 1 month and 1 year after surgery. RESULTS: In 35 out of 36 women (97.2%) that underwent vaginal hysterectomy and in nine out of 12 (75%) that underwent laparoscopic-assisted vaginal hysterectomy, we detected a high level of urethral mobility in the preoperative phase, compared with nine out of 39 (23.1%) women that underwent transabdominal hysterectomy. CONCLUSIONS: The results of our study allow us to confirm our starting hypothesis. Statistical analysis highlights that preoperative data are significantly different for the three types of hysterectomies, both as urethral mobility values (analysis of variance P