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Hyperthermic intraperitoneal chemotherapy (HIPEC) has been widely investigated in patients with peritoneal carcinomatosis, including those with epithelial ovarian cancer (EOC), with conflicting results. The hyperthermia enhances drug tissue penetration, synergizes with several cytotoxic drugs including cisplatin, degrades BRCA2, suppresses homologous recombination, and elicits an anticancer immune response. A meta-analysis of retrospective studies including both patients with primary advanced EOC and those with recurrent platinum-sensitive EOC failed to detect a benefit in terms of progression-free survival (PFS) or overall survival (OS) from the addition of HIPEC after surgery. The aim of the present review was to analyze the recent randomized clinical trials designed to assess the value of HIPEC in the management of patients with primary advanced EOC. Although not free from criticism and bias, the available data from two phase III trials seem to suggest that the addition of HIPEC to interval debulking surgery after neoadjuvant chemotherapy significantly improves PFS and OS. Conversely, HIPEC does not appear to offer any advantage after primary debulking surgery. Several phase III trials are currently ongoing on these issues and the use of HIPEC is still a matter of debate in the scientific community. Additional translational research is strongly warranted to detect biological variables able to identify a subset of patients who may have a major benefit from this therapeutic approach. In particular, the clinical outcome of patients who undergo HIPEC should be correlated with BRCA status and homologous recombination repair status.

Screening for ovarian cancer in the general population is a challenging issue. The aim of this review was to analyze both the studies based on serum CA125 assay and ultrasound (US) and the novel perspectives of clinical and biological research on this issue.The trials on the combination of serum CA125 and vaginal/pelvic US as well as the investigations on microRNA (miRNA)s, circulating tumor DNA and tumor protein 53 (TP53) variants in DNA purified from Pap smears have been critically analyzed.Two large randomized trials failed to detect a reduction in ovarian cancer-related deaths in women who underwent serum CA125- and US-based screening compared to those who had no screening. The United Kingdom Collaborative Trial of Ovarian Cancer Screening reported a 39.2% higher incidence of stage I-II and 10.2% lower incidence of stage III-IV disease in women who underwent annual multimodal screening with serum CA125 and vaginal US compared to women who had no screening, but this stage shifting did not translate into a survival benefit. A longitudinal, multiple biomarker algorithm-based strategy might improve ovarian cancer detection compared with serial CA125 alone. The use of serum tumor-associated autoantibodies, circulating tumor DNA and microRNA is still investigational. The identification of TP53 clonal variants in DNA purified from Pap smears can detect early steps of serous ovarian carcinogenesis.The availability of sensitive next-generation sequencing-based approaches for TP53 assessment in PAP smears may allow the reliability of this genetic marker for early detection of ovarian cancer to be verified.

Platinum/paclitaxel-based chemotherapy is able to obtain a clinical response in up to 80% of patients with advanced ovarian carcinoma, but most of them will subsequently develop recurrent disease. Several therapeutic approaches, including prolonged administration of the first-line regimen and the concomitant or sequential addition of a third cytotoxic agent to standard chemotherapy, failed to improve the clinical outcome of patients. In the last years, the implementation of the biological knowledge on ovarian carcinoma and the introduction of bevacizumab (BEV) and poly(ADP-ribose) polymerase inhibitors (PARPi) in first-line treatment have improved patient prognosis. In this review, we have analyzed the randomized clinical trials and real world observational studies on these issues, with the aim to suggest an algorithm for a rational use of BEV and PARPi in patients with newly diagnosed advanced ovarian carcinoma.

The aim of the study was to correlate the expression of mismatch repairs proteins (MMR), programmed-death-ligand1 (PDL-1), and estro-progestinic receptors (ER/PgR) in tissue samples from a series of cervical adenocarcinoma (ADC) patients with their clinicopathological features.Thirty-nine ADC specimens were retrospectively retrieved from the Division of Pathology of the University Hospital of Pisa from 2015 to 2021. Histological subtype, grade (G), Silva pattern, presence of lymph vascular space invasion (LVI), and perineural invasion (PNI) were annotated. On representative samples, immunostaining for ER/PgR, MLH1, PMS2, MSH2, MSH6, and PDL-1(sp142) was performed.Thirty-five ADCs were HPV-associated usual type (24 invasive and 11 in situ), 2 were clear cell type, one was a minimal deviation adenocarcinoma (MDA), and one was an invasive stratified mucin-producing carcinoma (iSMC). ADC associated with LVI were mostly G2-3, whereas those associated also with PNI were G3 with Silva pattern C. No difference in the expression of ER/PgR was observed with a dichotomic age stratification (51 years) of patients. Only 6 ADCs were MMR-deficient, all of them were of the usual type (4 invasive and 2 in situ). The heterodimer MLH-1/PMS2 was the one most frequently altered (5/6), whereas only one case had MSH6 loss. None of ADCs express PDL-1, except iSMC which showed PDL-1 expression1% in neoplastic cells.Both invasive and in situ usual type ADCs indicate MMR deficiency, highlighting how this could be an early event in tumorigenesis. None of the cases, except for iSMC, express PDL-1.

Background/aim The aims of the study were: i) to assess the incidence of perineural invasion (PNI) in squamous cell carcinoma of the vulva and ii) to correlate PNI with common pathological prognostic variables and clinical outcome of patients. Patients and methods The hospital records of 64 patients with vulvar squamous cell carcinoma who underwent primary radical surgery were reviewed. Results PNI was significantly related to stage (p=0.038), size (p=0.038), lymph-vascular space involvement (p=0.013) and nodal status (p=0.038), but not to patient age, tumor grade and stromal invasion. Five-year disease-free survival was 30.0% in patients with PNI and 53.1% in those without PNI (p=0.018), and the corresponding 5-year overall survival was 50.0% and 77.1% (p=0.031), respectively. Conclusion PNI was associated with common pathological prognostic variables and with a poorer clinical outcome in patients with vulvar squamous cell carcinoma.

The evaluation of the whole skeletal muscle area at the level of the third lumbar vertebra on computed tomography (CT) scans has often detected loss of skeletal muscle mass, defined as sarcopenia, and reduced skeletal muscle radiation attenuation (SMRA) in patients with different malignancies. Baseline sarcopenia has been detected in 33.3%-51.8% of patients with advanced cervical cancer, 33.6%-50% of those with endometrial cancer, and 11%-64% of those with advanced ovarian cancer. We reviewed the literature data on the clinical relevance of CT-assessed skeletal muscle status in gynecological malignancies. Overall, baseline skeletal muscle index and SMRA have an uncertain prognostic relevance, whereas their changes during treatment usually correlate with progression-free survival and overall survival. Multicenter clinical trials are strongly warranted to assess the effects of pharmacological agents and physical exercise in the management of skeletal muscle damage in patients with gynecological cancer.

To assess response rates and survival in patients with recurrent platinum-sensitive epithelial ovarian cancer (EOC) who received PARP inhibitor (PARP-i) maintenance and who subsequently underwent salvage chemotherapy for disease progression after PARPi.This retrospective investigation analyzed 103 patients who were treated in five Italian Gynecologic centers. The PARPi used was olaparib in 46 patients, niraparib in 55, and rucaparib in 2. The interval time between the last cycle of pre- PARPi platinum-based chemotherapy and the diagnosis of progression during PARPi maintenance was defined as platinum-free interval (PFI).Of the 28 patients with PFI6 months, 23 received chemotherapy (non-platinum single agent, 20; trabectedin + pegylated liposomal doxorubicin (PLD), 3). Forty-two of the 43 patients with PFI 6-12 months underwent chemotherapy (platinum-based chemotherapy,11; trabectedin + PLD, 10; non platinum-single agent, 21). Thirty-one of the 32 patients with PFI12 months received chemotherapy (platinum-based chemotherapy, 23; trabectedin + PLD, 3; non platinum - single agent, 5). An objective response was found in 13.0%, 26.2% and 41.9 % of the patients with PFI6 months, 6-12 months, and12 months (p= 0.03), respectively, and the corresponding median survivals after PARPi were 8.9 months, 17.5 months and 24.1 months (p= 0.002), respectively.Before the PARPi era, some randomized trials on platinum rechallenge in patients with recurrent EOC after more than 6 months from the last platinum cycle have shown response rates ranging from 47.2% to 66%. Response rates to chemotherapy for progression after PARPi appear to be lower than those expected according to PFI.

Concurrent cisplatin-based chemotherapy and radiotherapy (CCRT) plus brachytherapy is standard treatment for locally advanced cervical cancer. Platinum-based neoadjuvant chemotherapy (NACT) followed by radical hysterectomy has been proposed as an alternative approach, especially for patients with stage Ib2-IIb disease. This review analyzes the most commonly used combination regimens in this clinical setting and the randomized trials comparing chemo-surgery versus definitive radiotherapy or CCRT. The combination of paclitaxel plus ifosfamide plus cisplatin (TIP regimen) obtained the highest rates of optimal pathological response, associated with elevated hematological toxicity. In a recent phase II study, a dose-dense regimen consisting of weekly paclitaxel plus carboplatin for 9 cycles has achieved optimal pathological response rates similar to those of TIP with better toxicity profile. Further studies are strongly warranted to better define the optimal regimen for the patients selected to receive NACT followed by radical surgery.

Simple Summary Patients with metastatic or recurrent endometrial cancer (EC) not suitable for surgery and/or radiotherapy are candidates for pharmacological treatment with unsatisfactory clinical outcomes. The combination of carboplatin + paclitaxel is the standard first-line chemotherapy, whereas hormonal therapy is sometimes used in selected patients with slow-growing steroid receptor-positive EC. The combination of endocrine therapy with mTOR inhibitors or cyclin-dependent kinase 4/6 inhibitors is currently under evaluation. Immune checkpoint inhibitors, and especially pembrolizumab and dostarlimab, have achieved an objective response in 27–47% of highly pretreated patients with microsatellite instability-high/mismatch repair (MMR)-deficient EC. Abstract Patients with metastatic or recurrent endometrial cancer (EC) not suitable for surgery and/or radiotherapy are candidates for pharmacological treatment frequently with unsatisfactory clinical outcomes. The purpose of this paper was to review the results obtained with chemotherapy, hormonal therapy, biological agents and immune checkpoint inhibitors in this clinical setting. The combination of carboplatin (CBDCA) + paclitaxel (PTX) is the standard first-line chemotherapy capable of achieving objective response rates (ORRs) of 43–62%, a median progression-free survival (PFS) of 5.3–15 months and a median overall survival (OS) of 13.2–37.0 months, respectively, whereas hormonal therapy is sometimes used in selected patients with slow-growing steroid receptor-positive EC. The combination of endocrine therapy with m-TOR inhibitors or cyclin-dependent kinase 4/6 inhibitors is currently under evaluation. Disappointing ORRs have been associated with epidermal growth factor receptor (EGFR) inhibitors, HER-2 inhibitors and multi-tyrosine kinase inhibitors used as single agents, and clinical trials evaluating the addition of bevacizumab to CBDCA + PTX have reported conflicting results. Immune checkpoint inhibitors, and especially pembrolizumab and dostarlimab, have achieved an objective response in 27–47% of highly pretreated patients with microsatellite instability-high (MSI-H)/mismatch repair (MMR)-deficient (-d) EC. In a recent study, the combination of lenvatinib + pembrolizumab produced a 24-week response rate of 38% in patients with highly pretreated EC, ranging from 64% in patients with MSI-H/MMR-d to 36% in those with microsatellite stable/MMR-proficient tumors. Four trials are currently investigating the addition of immune checkpoint inhibitors to PTX + CBDCA in primary advanced or recurrent EC, and two trials are comparing pembrolizumab + lenvatinib versus either CBDCA + PTX as a first-line treatment of advanced or recurrent EC or versus single-agent chemotherapy in advanced, recurrent or metastatic EC after one prior platinum-based chemotherapy.

To assess the prognostic relevance of baseline and post-treatment skeletal muscle index (SMI) and skeletal muscle radiation attenuation (SMRA) at the level of third lumbar vertebra in patients with ovarian cancer who underwent primary surgery and platinum-based chemotherapy.This retrospective investigation analyzed 134 patients who underwent staging computed tomography, surgery, chemotherapy and post-treatment computed tomography.At univariate analysis, stage (p0.0001), histotype (p=0.01), residual disease (p0.0001) and treatment response (p0.0001) correlated with progression-free survival (PFS), whereas age (p=0.004), stage (p=0.006), residual disease (p0.0001) and treatment response (p0.0001) were associated with overall survival (OS). Neither baseline nor post-treatment SMI and SMRA had prognostic relevance. At multivariate analysis, residual disease and treatment response correlated with PFS (p0.0001 and p0.0001) and OS (p=0.007 and p0.0001), whilst age was an independent prognostic variable for OS (p=0.02).Baseline and post-treatment SMI and SMRA did not correlate with patient outcome in this clinical setting.

Simple Summary The development of hypersensitivity reactions to platinum agents in patients with gynecological cancers limits the use of platinum re-treatment for recurrent disease. In those patients who developed a hypersensitivity reactions during treatment with platinum agents it could be safer to undergo allergy diagnosis. This approach includes the in-vivo skin tests before re-exposure to the platinum agent, especially in those patients who have to undergo a 2nd or 3rd line therapy. In our experience, skin test for platinum agents resulted in a simple and sensitive tool for the diagnosis and prevention of hypersensitivity reactions to platinum agents. In addition, this approach identified a sub-group of patients that became sensitized to the platinum agent during the previous platinum-based therapy. Abstract Background: Hypersensitivity reactions (HSR)s to platinum agents are increasing in frequency, due to their extensive use and repeated exposures in patients with increased life expectancy. The aims of our study are to analyze the frequency of both type I and type IV HSRs in patients with gynecological cancer treated with (CBDCA) carboplatin and/or (CDDP) cisplatin, to evaluate the role of skin tests in the diagnosis and prevention of HSRs. Methods: From 2011 to 2018, we evaluated 124 consecutive female patients previously treated with CBDCA and/or CDDP for gynecological cancer. All patients, including those with and without HSR to previous platinum-based therapy, underwent in-vivo skin tests for platinum agents before starting the second or more therapeutic lines. To reduce the risk of false negative results, patients with a negative skin test at the first evaluation were re-tested after 3 weeks from the platinum re-exposure. Results: Among the 124 patients evaluated, 58 (47%) experienced HSRs to at least one platinum agent: 35% were to CBDCA, 5% to CDDP, 7% to both. Fifty-six of the 58 HSRs were classified as immediate and two delayed. Skin tests confirmed an IgE-dependent mechanism in 67% of patients with immediate-HSRs to CBDCA and identified a cross-reactivity between platinum agents in 18% of patients. Moreover, among those who had never developed an HSRs during platinum-based therapy, in-vivo skin tests identified 12% of sensitized patients. Conclusions: On the basis of our findings, skin test for platinum agents is a simple and sensitive tool for the diagnosis and prevention of HSRs to CBDCA and/or CDDP and can be useful for detecting possible cross-reactivity among platinum agents.

Background/aim The aim of the study was to assess the clinical outcome of patients with malignant transformation of an ovarian mature teratoma. Patients and methods This study was conducted on 23 patients who underwent primary surgery at three Italian Gynecological Centers. Histologically, nine (39.1%) patients had squamous cell carcinoma, five (21.7%) had a thyroid carcinoma, six (26.1%) had a carcinoid, one (4.3%) patient had papillary renal carcinoma, one (4.3%) had medulloblastoma and one (4.3%) had intestinal-type mucinous adenocarcinoma. Results All six patients with stage I squamous cell carcinoma had no evidence of disease (NED) after a median time of 141 months. Of the three patients with stage IIb-IIIc squamous cell carcinoma, two had NED after 119 and 154 months, and one died of the disease 9 months after diagnosis. All five women with stage I thyroid carcinoma had NED after a median of 60 months. Of the six patients with stage I carcinoid, five had NED after a median of 168 months, whereas one died due to carcinoid heart disease. The three patients with stage I renal carcinoma, medulloblastoma and mucinous adenocarcinoma had NED after 24, 141 and 149 months, respectively. Conclusion The clinical outcome of early-stage malignancies associated with mature ovarian teratomas is excellent following treatment.

Mature cystic teratomas of the ovary have an incidence of 1.2-14.2 cases per 100.000 people per year. Malignant transformation occurs in approximately 2% of the cases, and usually consists of squamous cell carcinoma. The preoperative detection is difficult and the diagnostic accuracy of ultrasound, magnetic resonance imaging, and computed tomography is debated. The diagnosis is frequently made in the operating room or on final histological examination. Standard treatment consists of bilateral salpingo-oophorectomy, total hysterectomy and comprehensive surgical staging in early disease and optimal cytoreductive surgery in advanced disease. Paclitaxel/carboplatin- based chemotherapy is the most used adjuvant treatment, whereas more aggressive regimens can be adopted in patients with high tumor burden or recurrent disease. The efficacy of radiotherapy is still unproven. The prognosis is poor when the tumor has spread beyond the ovary. There are few information to provide commonly accepted guidelines for this malignancy.

Background/aim To assess the prognostic relevance of volume-based parameters [whole body (wb)-metabolic tumor volume (MTV) and wb-total lesion glycolysis (TLG)] of pretreatment PET/CT in patients with potentially platinum-responsive recurrent ovarian cancer. Patients and methods This retrospective investigation analyzed 67 patients at first relapse. Results At univariate analysis, post-relapse survival and overall survival correlated with residual disease after primary surgery (RD) (p=0.015 and 0.049, respectively), time to recurrence (p=0.005 and p=0.0003), number of recurrence sites (p=0.001 and p=0.0005), treatment at recurrence (p=0.044 and 0.043) and wb-MTV (p=0.023 and 0.021) but not with wb-TLG. RD, time to recurrence and number of recurrence sites, but not wb-MTV, were independent prognostic variables for post-relapse survival, and time to recurrence and number of recurrence sites, but not wb-MTV, were independent prognostic factors for overall survival. Conclusion Volume-based parameters of PET/CT are not independent predictors of clinical outcome in potentially platinum-responsive recurrent ovarian cancer.

Background Perivascular epithelioid cell tumors (PEComa)s are mesenchymal neoplasms located at various anatomic sites, which usually express both melanocytic and myogenic markers. Case report A 60-year-old woman underwent laparotomy for a huge, heterogeneous, right ovarian mass. The histological examination of the surgical specimen revealed a neoplasm consisting of both cells with clear or eosinophilic cytoplasm and spindle cells in a myxoid stroma. Immunostaining was positive for human melanoma black-45, h-caldesmon, desmin, actin, and transcription factor 3. Cell atypias were moderate, mitoses were 4/10 high power fields (HPF) and margins were focally infiltrative. These findings pointed to a diagnosis of ovarian PEComa. Twenty-five months later, two subcutaneous lesions were surgically removed on the left trapezius muscle and the median subumbilical area, respectively. The former was a desmoid fibromatosis, whereas the latter was a recurrence of PEComa with greater nuclear pleomorphism and higher number of mitoses (26/50 HPF) compared to the primary tumor. The patient was free of disease 11 months later. Conclusion A long-term follow-up of gynecological PEComas is strongly recommended.

Introduction: Colon cancer (CC) and epithelial ovarian cancer (EOC) are common and severe neoplasms frequently sharing a massive inflammatory involvement of peritoneum. A detailed molecular characterization of such carcinomatosis has not been performed, so far. Methods: Omental adipocytes were isolated from thirty-three adult women who underwent primary surgery for CC or EOC. Expression of several pro-inflammatory genes was determined by real-time PCR and immunofluorescence. Data were related to the clinical phenotype of the patients. Results: CD68, FGFR1, and IL-6 were significantly more expressed in adipocytes from CC patients and VEGF in adipocytes from EOC. TNFα, TGFβ, or MCP-1, as well as the pro-inflammatory platform P2X7R-NLRP3, did not differ between the 2 cancers. White blood cell count, mirroring systemic inflammation, was related to adipocyte P2X7R (R = 0.508, p = 0.003), NLRP3 (R = 0.405; p = 0.02), and MCP-1 (R = 0.448; p = 0.009). P2X7R and NLRP3 were the only inflammatory factors significantly more expressed in patients carrying both omental and peritoneal carcinosis, who were also characterized by a higher leukocytosis. None of the tested inflammatory markers was associated with tumor grading for both neoplasms; however, the presence of metastases was associated with a higher adipocyte expression of FGFR1 and TGFβ. Conclusion: We show here that rarely measured molecules seem to specifically characterize omental carcinomatosis of CC or EOC, while more common inflammatory agents like TNFα, TGFβ, or MCP-1 do not; the P2X7R-NLRP3 complex marks omental and peritoneal carcinosis and is related to circulating white blood cells and MCP-1, involved in monocyte-macrophage tissue infiltration; increased TGFβ and FGFR1 characterize the tumoral dissemination.

Background/aim The role of neoadjuvant chemotherapy (NACT) is under investigation in locally advanced cervical cancer (LACC). Patients and methods A total of 49 patients with FIGO stage IB1-IIB cervical cancer who underwent two different regimens of weekly dose-dense NACT were included. The objective was to evaluate clinical/pathological response and toxicity profile. Results A clinical complete response and partial response were obtained in 43 patients with a clinical overall response rate of 88%. Among the 42 surgically treated patients, 7 (17%) and 35 (83%) achieved a pathological overall optimal response and a suboptimal pathological response, respectively. G3-G4 neutropenia occurred in 16% of patients, whereas no cases of G3 thrombocytopenia, G3 anemia and febrile neutropenia were observed. Conclusion Dose-dense NACT is safe, has acceptable toxicity, and obtains good clinical response, but is less effective in terms of pathological overall optimal response rates compared to other regimens.

While cancer during pregnancy and its treatment has grown to be a popular topic in recent years, little is known on how to advise patients looking to conceive or conceiving after cancer treatment. The aim of this paper is to review the available literature on the impact of pregnancy on survivors of the most common childhood cancers, brain cancer, haematological malignancies, thyroid cancer, melanomas and sarcomas. Its main objective is to be a source of information for clinicians looking to counsel patients in these delicate moments exploiting all the available literature, albeit scarce. Given the available literature, we conclude that the presence of a multidisciplinary team is of great importance in supporting the patient and her loved ones when facing pregnancy with a previous cancer diagnosis.

Clear cell carcinoma of the ovary is a rare and distinct histotype of epithelial ovarian carcinomas. Women diagnosed with clear cell carcinomas are usually younger and diagnosed at earlier stages than those with the most common high-grade serous histology. Endometriosis is considered a main risk factor for the development of clear cell carcinoma of the ovary, and it can be considered a precursor of of this tumor, as it is identified in more than 50% of patients with clear cell carcinoma. Different molecular pathways and alterations heve been identified in ovarian clear cell carcinoma, including the most common mutations of AT-rich interaction domain 1A [ARID1A] and phosphatidylinositol-4,5-bisphosphate 3-kinase [PIK3] catalytic subunit alpha [PIK3CA]. The prognosis of patients at early stage is favorable, while patients with advanced or recurrent disease experience a poor oncologic outcomes. Despite a lower rate of responses due to an intrinsic chemoresistance, the treatment strategy for advanced disease resembles the treatment of high-grade serous carcinoma, which includes aggressive cytoreductive surgery and platinum-based chemotherapy. For this reason, the role of adjuvant chemotherapy in patients with stage I disease undergoing complete surgical staging is still under debate. Alternative treatments, including biological agents that target different pathways constitute the most promising treatment strategies, and well-designed, collaborative international trials should be designed in order to improve the oncologic outcomes and the quality of life of patients with this aggressive disease.

Steroid contraceptive hormones may promote human papilloma virus (HPV) - DNA integration into the host genome, may bind to specific HPV-DNA sequences within transcriptional regulatory regions, and may modulate cell apoptosis. Most epidemiological studies, reported in this narrative review, have shown that oral contraception is associated with a 1.5-3.3-fold higher relative risk of cervical carcer, but only in users for >5 years and especially in HPV-positive women. The relative risk declines with increasing time since last use and is not different from that of never users after >10 years. Ten-year oral contraceptive use from the age of 20 years is associated with an increase in the cumulative incidence of invasive cervical cancer at the age of 50 years of approximately 1 case per 1,000. Oral contraception has a very small negative impact on the absolute risk of cancer of the uterine cervix.

Simple Summary The aim of this review is to assess the available literature of the pharmacological treatment of patients with metastatic, recurrent or persistent cervical cancer not amenable by surgery or radiotherapy. The results and toxicities of cisplatin-based doublets are exhaustively described. The combinations of cisplatin plus paclitaxel with or without bevacizumab is the most active regimen in these clinical setting. Immune-check-point inhibitors and molecularly-targeted agents are promising fields of research. Abstract Cervical cancer patients with distant or loco-regional recurrences not amenable by surgery or radiotherapy have limited treatment options, and their 5-year overall survival (OS) rates range from 5% to 16%. The purpose of this paper is to assess the results obtained with chemotherapy and biological agents in this clinical setting. Several phase II trials of different cisplatin (CDDP)-based doublets and a phase III randomized trial showing a trend in response rate, progression-free survival, and OS in favor of CDDP + paclitaxel (PTX) compared with other CDDP-based doublets have been reviewed. The factors predictive of response to chemotherapy as well as the benefits and risks of the addition of bevacizumab to CDDP + PTX have been analyzed. The FDA has recently approved pembrolizumab for patients with recurrent or metastatic cervical cancer in progression on or after chemotherapy whose tumors were PD-L1 positive. Interesting perspectives of clinical research are represented by the use of immune checkpoint inhibitors alone or in addition to chemotherapy, whereas PARP inhibitors and PI3K inhibitors are still at the basic research phase, but promising.

Aim To assess the correlation between contrast-enhanced computed tomography (CE-CT) and positron-emission tomography (PET)/CT results and surgical and pathological findings in patients with recurrent platinum-sensitive ovarian cancer who underwent secondary cytoreduction. Patients and methods 18F-fluorodeoxyglucose (18F-FDG) PET/CT with/without CE-CT were performed before 56 cytoreductive surgeries in 49 patients with suspicious recurrent ovarian cancer. Results 18F-FDG PET/CT showed higher sensitivity and diagnostic accuracy compared with CE-CT for both the whole series (100% versus 90.6%, respectively, and 97.8% versus 85.3%), and the 24 cases in which both examinations were performed (100% versus 87.0% and, respectively, 95.8% versus 83.3%). The addition of CE-CT to 18F-FDG PET/CT did not improve its diagnostic reliability. Conclusion 18F-FDG PET/CT appears to be the more reliable imaging technique for the evaluation of patients with suspicious recurrent ovarian cancer, and for the selection of those more suitable for secondary cytoreductive surgery.

Background/Aim: The aim of the study was to assess the outcome of advanced ovarian cancer patients who i) underwent primary surgery followed by carboplatin/paclitaxel-based chemotherapy with or without bevacizumab, ii) were in complete response after chemotherapy, iii) and subsequently recurred. Patients and Methods: The hospital records of 138 complete responders after chemotherapy with (n=58) or without (n=80) bevacizumab were reviewed. Results: Both survival after recurrence and overall survival were related to age (=61 vs. >61 years, p=0.002 and p=0.0001), performance status (0 vs. =1, p=0.002 and p=0.001), histotype (serous vs. non serous, p=0.005 and p=0.01), time to recurrence (=12 vs.

Perineural invasion (PNI) is detected in 7.0-35.1% of cervical carcinomas. This histological finding correlates with cervical invasion, lymph-vascular space invasion (LVSI), tumor size, positive resection margins, parametrial invasion, node metastases and advanced stage. Some authors have reported that PNI has no prognostic relevance, others have found that PNI is related to disease-free survival or overall survival (OS) at univariate analysis, and others have observed that it is an independent poor prognostic factor for OS. The evaluation of PNI status should be included in the decision-making process for planning adjuvant treatment. PNI has been found in 7.6-52.4% of vulvar carcinomas. This feature, which is strongly associated with depth of invasion, LVSI, tumor size, advanced stage and nodal involvement, is an independent prognostic variable for the risk of recurrence and death in most series. PNI should be evaluated routinely in histopathology reports of vulvar carcinoma and could help clinicians to tailor adjuvant treatment.

ObjectiveThe objective of this retrospective study was to assess the clinical outcome of patients with advanced epithelial ovarian cancer in complete response after primary debulking surgery (PDS) or neoadjuvant chemotherapy followed by interval debulking surgery (IDS]).MethodsThe authors reviewed the hospital records of 384 patients who underwent PDS (n = 322) or IDS (n = 62) and who were in complete response after primary treatment.ResultsOptimal (residual disease [RD] < 1 cm) and complete (no gross RD) cytoreduction rates were higher after IDS than after PDS (71.0% vs 55.9%;P= 0.001 and 51.6% vs 35.7%, respectively;P= 0.02). Tumor recurred in 73.0% of the 322 complete responders after PDS versus 87.1% of the 62 complete responders after IDS (P= 0.01). The IDS group showed a higher recurrence rate within 6 months (11.3% vs 3.1%:P= 0.01) and a trend to higher recurrence rate between 6 and 12 months (30.6% vs 19.9%). Tumor recurred in 57.4% of the 115 completely cytoreduced patients after PDS versus 87.5% of the 32 completely cytoreduced patients after IDS (P= 0.001). The IDS group showed a trend to higher recurrence rate within 6 months (6.2% vs 1.7%) and a higher recurrence rate between 6 and 12 months (37.5% vs 15.6%;P= 0.01). Two-year, 5-year, and 7-year progression-free survival were 65.8%, 40.8%, and 39.3% for completely cytoreduced patients after PDS versus 43.8%, 12.5%, and 12.5% for completely cytoreduced patients after IDS (P= 0.001); and 2-year, 5-year, and 7-year overall survival were 96.4%, 69.3%, and 50.4% for the former versus 87.1%, 41.8%, and 32.6% for the latter (P= 0.001).ConclusionsThe clinical outcome of completely cytoreduced patients was significantly better for PDS group than for IDS group, and therefore, the achievement of no gross RD after surgery seemed to have a different prognostic relevance for the 2 groups.

Objective: To assess the clinical outcome of patients with high-risk early-stage endometrial cancer and negative pelvic nodes who received adjuvant platinum-based chemotherapy plus vaginal brachytherapy (VBT). Methods: This investigation assessed 80 patients who underwent hysterectomy, bilateral salpingo-oophorectomy, and pelvic lymphadenectomy for stage Ib-II, grade 2–3 endometrioid (n = 43) or stage Ia-II nonendometrioid (n = 37) endometrial cancer. Results: Five-year local control rate, 5-year disease-free survival, and 5-year overall survival were 97, 87, and 97%, respectively, for endometrioid carcinoma, and 66, 50, and 72%, respectively, for nonendometrioid carcinoma. Conclusions: This retrospective study appears to show that adjuvant platinum-based chemotherapy plus VBT achieve very good results in endometrioid carcinoma. This combined treatment seems to be less effective in nonendometrioid carcinoma.

Malignant transformation occurs in 1.5-2% of mature cystic teratomas (MCT)s of the ovary and usually consists of squamous cell carcinoma, whereas other malignancies are less common. Diagnosis and treatment represent a challenge for gynecologic oncologists. The preoperative detection is very difficult and the diagnostic accuracy of imaging examinations is uncertain. The tumor is usually detected post-operatively based on histopathologic findings. This paper reviewed 206 consecutive patients who underwent surgery for a histologically-proven MCT of the ovary between 2010 and 2017. Malignant transformation occurred in 3 (1.5%) of them, and consisted of squamous cell carcinoma in one, type 2 papillary renal carcinoma in one, and papillary thyroid carcinoma in another one. The paper reported the clinical, radiological and histological features of these cases and reviewed the literature data on the treatment options.

Aim To assess the patterns of recurrence and clinical outcomes of patients with cervical adenocarcinoma who underwent neoadjuvant platinum-based chemotherapy (NACT) followed by radical hysterectomy. Patients and methods Data were retrospectively analyzed for 82 patients with International Federation of Gynecology and Obstetrics stage Ib2-IIb cervical adenocarcinoma who underwent this chemo-surgical treatment. The median follow-up of survivors was 89 months (range=5-208 months). Results Pathological complete response, optimal response and suboptimal response with intra-cervical residual disease were obtained in five (6%), 10 (12%) and 36 (44%) patients, respectively. Adjuvant external-beam radiotherapy with or without concurrent chemotherapy was administered to 47 patients. Nineteen (23%) out of the 82 patients experienced recurrence after a median of 12 months (range=5.3-86.8 months). Recurrent disease was pelvic in 12 (63%) patients, extra-pelvic in five (26%), and both pelvic and extra-pelvic in two (10%). According to pathological response, tumor relapsed in 10% of optimal responders, 14% of sub-optimal responders with intra-cervical residual disease, and 36% of sub-optimal responders with extra-cervical residual disease or non-responders. Five-year recurrence-free and overall survival were 77% and 84%, respectively. Patients who achieved an optimal response or sub-optimal response with intra-cervical residual disease had better 5-year recurrence-free (87% vs. 64%, p=0.017) and overall (92% vs. 74%, p=0.012) survival than those who had sub-optimal response with extra-cervical residual disease or no response. The latter had a 1.441-fold higher risk of recurrence and a 1.652-fold higher risk of death than those who obtained an optimal response or a sub-optimal response with intra-cervical residual disease. Conclusion NACT followed by radical hysterectomy may be an option for patients with stage Ib2-IIb adenocarcinoma of the uterine cervix.

BACKGROUND/AIM To assess the patterns of recurrence of node-positive endometrial cancer patients. PATIENTS AND METHODS This investigation assessed 82 patients who received different postoperative treatments. RESULTS Recurrence developed in 36 patients after a median time of 13.5 months, and involved the vagina, pelvic nodes, para-aortic nodes and distant sites in 5, 8, 16 and 17 patients, respectively. Five-year progression-free survival (PFS) and 5-year overall survival (OS) were 51.1% and 59.8%. PFS and OS were significantly better for endometrioid than for non-endometrioid tumors. There was a trend towards a better outcome for patients who underwent chemotherapy±radiotherapy compared to those who received radiotherapy alone. Among the former, there was a better 5-year PFS (65.8% versus 33.7%, p=0.038) in patients who received platinum/paclitaxel-based regimens compared to those who received platinum-based chemotherapy. CONCLUSION Disease recurred in 43.9% of patients, and platinum/paclitaxel-based chemotherapy plus radiotherapy appeared to be the best adjuvant treatment.

Aim To assess preliminary results with dose-dense neoadjuvant chemotherapy (NACT) prior to surgery or concurrent chemo-radiotherapy (CCRT) in cervical cancer. Patients and methods Thirty patients received weekly paclitaxel (80 mg/m2) plus carboplatin (AUC2) for 6 cycles followed by radical hysterectomy in 16 (stage Ib2-IIb), conisation in one (stage Ib1), and CCRT in 13 (stage Ib2-IIb). Median follow-up of survivors was 12 months (range=3-22). Results Among the surgically treated patients, clinical overall response rate (RR) was 82.3%, optimal pathological RR was 17.6%, and suboptimal pathological RR with intra-cervical residual disease was 41.2%. Only one patient relapsed. Among the CCRT treated patients, partial RR after NACT was 76.9% and complete RR after CCRT was 58.3%. However, 42.8% of complete responders recurred. Toxicity was acceptable. Conclusion Dose-dense NACT seems to achieve promising RRs with manageable toxicity in cervical cancer. Investigation on larger series with longer follow-up is warranted.

Objectives The purpose of this retrospective multicenter study was to correlate patterns of recurrences and clinical outcome of cervical cancer patients who underwent neoadjuvant chemotherapy [NACT] to surgery. Methods This study was conducted on 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent NACT to surgery with pelvic lymphadenectomy. The median follow-up was 66.5 months (range, 8-212 months). Overall optimal response rate was the sum of complete and optimal partial response rates. Results An overall optimal response was obtained in 64 patients (19.2%). As for the 220 sub-optimal responders (66.1%), 127 patients had negative nodes and negative parametria and/or surgical margins, 75 patients had positive nodes with positive or negative parametria and/or surgical margins, and 18 patients had positive parametria and/or surgical margins with negative nodes. At the time of the present analysis, 79 (23.7%) of the 333 patients had a recurrence after a median time of 14.9 months (range, 4.5-123 months). Recurrent disease was pelvic in 50 (63.3%), extra-pelvic in 22 (27.9%), and both in 7 (8.8%). On multivariate analysis, pathological response to NACT was an independent prognostic variable for recurrence-free and overall survival. Patients who did not achieve an overall optimal response had a 2.757-fold higher risk of recurrence and a 5.413-fold higher risk of death than those who obtained an overall optimal response. Conclusions Results appear to suggest that the chemo-surgical approach is an effective therapeutic option for patients with stage Ib2-IIb cervical cancer and that pathological response to NACT is the strongest prognostic factor for the outcome. © 2013 Elsevier Inc.

To assess prognosis of gestational trophoblastic neoplasia (GTN) and obstetric outcome after chemotherapy.Sixty-six patients had diagnosis of hydatiform mole on curettage and 18 developed GTN. Two patients were referred with pathological diagnosis of GTN. Chemotherapy was tailored according to International Federation of Gynecology and Obstetrics risk scoring system.All patients with GTN but one, were recovered by chemotherapy and had no evidence of disease after a median follow-up of 80 months. Only the patient with epithelioid trophoblastic tumor died of disease. Seven out of the eight women who tried to conceive after chemotherapy became pregnant. Ten conceptions occurred, resulting in no molar pregnancy, three miscarriages and seven term-live healthy births (70.0%). All seven babies showed normal development and growth after a median follow-up of 38 months.The prognosis of women with GTN is very good, and obstetric outcomes of those who conceive after chemotherapy are similar to those of the general population.

High-risk human papillomaviruses (HPVs) are involved in the etiopathogenesis of cervical intraepithelial neoplasia (CIN) and cervical cancer. After taking HPV into account, smoking habit appears to be the most significant environmental risk factor, and the risk of this malignancy increases significantly with intensity and duration of smoking. Women with human immunodeficiency virus (HIV) infection experience a higher incidence of CIN and invasive cervical cancer. Among HIV+ women, the highly active antiretroviral therapy increases the regression rate of CIN, but the majority of these lesions do not regress to normal. As far as oral contraceptives (OCs), a systematic review of 28 studies found that, compared with never pill users, the relative risk (RR) of cervical cancer increased with increasing duration of OC use. The results were similar for squamous cell carcinoma and adenocarcinoma, and the RRs decreased after pill discontinuation. However, by weighing risks and benefits, the World Health Organization does not recommend any change in OC practice. There is no correlation between hormone replacement therapy and cervical cancer. Experimental data have shown that estradiol and progesterone can modulate the host immune response to HPV16. Prophylactic vaccination in conjunction with cervical screening is the best prevention strategy for cervical cancer.

BRCA1 and BRCA2 mutation carriers have a 54-85% and 45% lifetime risk of developing breast cancer, respectively, and a 18-60% and 11-27% lifetime risk of developing ovarian cancer, respectively. Oral contraceptives (OCs) significantly reduce the risk of ovarian cancer also in BRCA1/BRCA2 mutation carriers. The association between OC use and breast cancer risk in these women is controversial. Some studies showed a modestly increased risk especially among BRCA1 mutation carriers. The risk appears to be greater for women who took OCs for at least 5 years and who took OCs before the age of 30 years. Other studies reported that duration of use before first full-term pregnancy has a positive association with breast cancer risk. Salpingo-oophorectomy reduces the risk of coelomic epithelial cancer of 80-95% and the risk of breast cancer of approximately 50%. BRCA1 and BRCA2 mutation carriers should be encouraged to undergo prophylactic bilateral salpingo-oophorectomy at the age of 35-40 years or when childbearing is complete. Short-term use of hormone replacement therapy may relieve menopausal symptoms and does not appear to affect the breast cancer risk reduction obtained with salpingo-oophorectomy.

Major extensive surgery still represents a cornstone of therapy of gynaecological cancer, and the adoption of implemented clinical guidelines for perioperative management can significantly decrease patient morbidity and mortality and reduce hospital stay. The overall risk of deep venous thrombosis in patients undergoing gynaecological surgery ranges from 7% to 45%, and fatal pulmonary embolism occurs in approximately 1% of these women. A meta-analyses of randomised trials showed a significant decrease in deep venous thrombosis in women receiving unfractioned heparin [UFH] compared with controls, and revealed no significant difference in deep venous thrombosis and pulmonary embolism between patients who received UFH and those who received low-molecular weight heparin [LMWH]. Potential advantages favouring LMWH over UFH include once-daily versus repeated daily injections and a lower risk of heparin-induced thrombocytopenia. All patients undergoing major surgical operations should receive LMWH that should be started preoperatively and then given for 7-10 days at least and prolonged for up to 4 weeks in high-risk cases. Antithrombotic mechanical methods can be added to pharmacological agents, but should not been used alone. Cephalosporins and amoxicillin-clavulanic acid have been widely used in gynaecological surgery prophylaxis. Both amoxicillin-clavulanic acid and cefazolin have good in vitro activity against the microbes more frequently involved in postoperative infections, such as Gram-negative bacilli, but amoxicillin-clavulanic acid is more effective against anaerobes. A single dose of antibiotics has been shown to be as effective as multiple doses in many trials that have compared a single-dose regimen with a multiple-dose regimen. Amoxicillin-clavulanic acid prophylaxis at the induction of anaesthesia can be suggested for gynaecological cancer patients undergoing major gynaecological surgery with or without colorectal resection. An additional antibiotic dose is recommended for prolonged operations or when intraoperative blood loss is important. Cephalosporins can be administered to women with a history of penicillin allergy not manifested by an immediate hypersensitivity reaction, whereas tigecyclin should be reserved to patients with a prior anaphylactic reaction to beta-lactams. Recent meta-analyses of randomised trials on patients undergoing elective colorectal surgery found more anastomotic leakages in patients who had preoperative mechanical bowel preparation with oral administration of different solutions than in those who had not, whereas there were no significant differences between the two arms as for wound infections, other septic complications, and non-septic complications. Therefore, preoperative mechanical bowel cleansing is not warranted for gynaecological cancer patients scheduled for surgery that may involve colon-rectum. After major abdominal gynaecological surgery, early oral feeding (within the first 24h regardless of the resolution of postoperative ileus) appears to be associated with increased nausea, shorter time to the presence of bowel sound, shorter time to first solid diet, and a trend toward shorter hospital stay when compared with delayed feeding. Since early oral feeding is safe but associated with increased nausea, the decision whether to adopt this postoperative regimen should be individualised. Decision making processes about thromboprophylaxis, antibiotic prophylaxis, bowel preparation for surgery that may involve colon-rectum, and timing of postoperative oral feeding will become more and more relevant for improved safety and quality of life of women with gynaecological cancer.

The surveillance of ovarian cancer patients after initial treatment is a challenging question in clinical practice. Serum CA 125 assay, physical examination, and imaging examinations have been employed with different time schedules for the follow-up of asymptomatic patients. Rising serum CA 125 levels may precede the clinical detection of relapse in 56-94% of cases with a median lead time of 3-5 months. An ongoing randomised phase III European trial is comparing the benefits of early administration of chemotherapy based on serum CA 125 assay alone versus delaying treatment until clinical or radiological detection of recurrent disease. Physical examination, with or without ultrasound, is very useful for the surveillance of these patients, since approximately 25-50% of relapses involve the pelvis. Additional radiological imaging techniques, such as computed tomography (CT) and magnetic resonance imaging (MRI), are usually performed in asymptomatic patients with rising CA 125 levels as well as in patients with suspicious symptoms or signs. Integrated positron emission tomography (PET) and CT scanners (PET/CT) can identify recurrent disease in tissues that appear normal at CT imaging as well as metastatic lesions intimately associated with the bowel wall that are difficult to detect with CT or MRI, so that in most series PET/CT has a higher diagnostic reliability than that of conventional imaging techniques. Moreover, PET/CT can disclose unusual supra-diaphragmatic spreading of the disease and may be very helpful for treatment planning, especially for the selection of patients suitable for secondary surgical cytoreduction. A prospective, randomised trial of therapeutic interventions based on stratification by PET/CT disease status could elucidate the real impact of this diagnostic procedure in the management of patients with recurrent ovarian cancer.

The aim of this retrospective investigation was to assess the pattern of failures of 412 patients with recurrent ovarian cancer followed up with different surveillance protocols.Time to recurrence was less than 6 months in 98 women (23.8%), 6 to 12 months in 102 women (24.7%), and more than 12 months in 212 women (51.5%). Symptoms at relapse were referred by 81 women (19.7%). Among the 331 asymptomatic patients, the surveillance procedure that raised the suspect of recurrent disease was clinical examination in 49 (14.8%), imaging technique in 90 (27.2%), serum CA 125 in 77 (23.3%), and both serum CA 125 and imaging technique in 115 (34.7%). At univariate analysis, survival from initial diagnosis was related to stage (P = 0.004), residual disease after initial surgery (P < 0.0001), time to recurrence (P < 0.0001), site of relapse (P = 0.04), and treatment at recurrence (P < 0.0001), and survival after recurrence was related to stage (P = 0.01), residual disease (P < 0.0001), time to recurrence (P < 0.0001), and treatment at recurrence (P < 0.0001). Conversely, symptoms at recurrence had no prognostic relevance. Cox proportional hazards model showed that residual disease and time to recurrence were the only independent prognostic variables for both survival from initial diagnosis (P < 0.0001) and survival after recurrence (P < 0.0001). In conclusion, there was no survival difference between asymptomatic and symptomatic patients at the time of relapse, and therefore, the diagnostic anticipation allowed by a scheduled follow-up protocol did not seem to improve the clinical outcome of patients who ultimately developed recurrent disease.

Carboplatin (Carbo-Pt), an alkylating agent cleared from the plasma through glomerular filtration, is commonly used for the treatment of ovarian cancer. When administered at high dosage or to patients with reduced renal function, Carbo-Pt may be nephrotoxic. The dose of Carbo-Pt is calculated with Calvert formula, using the value of 24-hour creatinine clearance (24h Ccr) as an estimate of glomerular filtration rate (GFR). The aim of this study was to evaluate the possibility of individualizing the dose of Carbo-Pt using an alternative method to estimate GFR, based on body composition analysis, and then to assess the nephrotoxicity of Carbo-Pt therapy individualized with this new method. First, we evaluated the agreement between GFR (renal clearance of diethylene triamine pentaacetic acid (99mTc-DTPA)), 24h Ccr, and the new estimate of GFR (BCMGFR) calculated on the basis of individual values of body cell mass (BCM) and plasma creatinine. BCMGFR gave a better estimate of GFR than 24h Ccr. Then, we evaluated the nephrotoxicity of a combination chemotherapy based on Carbo-Pt (AUC(5-6)) in 23 patients affected by ovarian cancer. The dose of Carbo-Pt was adjusted to residual renal function of patients, evaluated as BCMGFR. No case of acute renal failure was observed with this treatment regimen. Urinary excretion of proteins (albumin, beta2-microglobulin, and retinol-binding protein) and tubular enzymes, measured as markers of tubular damage, increased significantly and transiently only in the first days after chemotherapy, whereas no evidence of chronic nephrotoxic effect was documented. Dose individualization, using the value of BCMGFR, may minimize nephrotoxicity due to Carbo-Pt therapy.

Molecular targeted therapies represent an interesting field of pharmacological research in endometrial cancer. The loss of PTEN (phosphatase and tensin homolog deleted on chromosome 10) function, with consequent activation of the PI3K (phosphatidylinositol-3-kinase)-AKT (serine/threonine-specific protein kinase)-mTOR (mammalian target of rapamycin) signaling pathway, occurs in 32-83% of endometrioid-type endometrial carcinomas, thus suggesting a role for mTOR inhibition in this malignancy. Some analogues of rapamycin (CCI-799, RAD-001, AP-23573) have been developed and tested in different tumors including endometrioid-type endometrial carcinoma. For example, AP-23573 achieved a clinical benefit response in 33% of 27 heavily pretreated patients, and CCI-799 obtained a 26% partial response rate and a 63% stable disease rate in 19 patients. Overexpression of ErbB-2 (epidermal growth factor type II receptor) has been detected in 18-80% of uterine papillary serous carcinomas (UPSCs), thus providing a biological rationale for the use of trastuzumab in these aggressive tumors. UPSC often overexpresses claudin-3 and claudin-4, which represent the epithelial receptors for Clostridium perfringens enterotoxin (CPE). CPE-mediated therapy might be a novel treatment modality for UPSC resistant to chemotherapy. A better understanding of the signaling transduction pathways that are dysregulated in endometrioid-type endometrial carcinoma and UPSC will allow the development of novel molecular targeted therapies.

Gestational trophoblastic disease includes complete hydatidiform mole (CHM) or partial hydatidiform mole (PHM) and gestational trophoblastic neoplasia (GTN). Given the very high-curability rate of trophoblastic disease, the risk of further molar pregnancy after CHM or PHM as well as the risk of second primary tumors and fertility compromise after chemotherapy for GTN represent major concerns. The incidence of subsequent molar pregnancy ranges from 0.7 to 2.6% after one CHM or PHM, and is approximately 10% after two previous CHMs. Among patients who have received chemotherapy, there is an increased risk of myeloid leukemia which is mainly related to the cumulative dose of etoposide. Resumption of normal menses occurs in approximately 95% of women treated with chemotherapy, but menopause occurs 3 years earlier compared with those non-treated with chemotherapy. Term live birth rates higher than 70% without increased risk of congenital abnormalities have been reported in these women, and pregnancy outcomes are comparable to those of general population, except a slightly increased risk of stillbirth. Fertility-sparing treatment for placental site trophoblastic tumor is a therapeutic option reserved to highly selected, young women who do not present markedly enlarged uterus or diffuse multifocal disease within the uterus.

To correlate CA125 levels after platinum- and paclitaxel-based chemotherapy with progression-free survival (PFS) and overall survival (OS) in advanced ovarian carcinoma following primary cytoreduction.The study was conducted on 247 patients.By log-rank test, PFS and OS were related to performance status (PS) (p=0.04 and p=0.00002), residual disease (p=0.00002 and p=0.001), ascites (p=0.00001 and p=0.0003) and post-chemotherapy CA125 using 10.8 U/ml as cut-off (p=0.0001 and p=0.01). PFS was related to post-chemotherapy CA125 assay (cut-off values of 7.1 U/ml (p=0.02), 18.5 U/ml (p0.000001) and 35.0 U/ml (p=0.0001)). OS was related to FIGO stage (p=0.02). On multivariate analysis, residual disease, ascites and post-chemotherapy CA125 with any selected cut-off were independent prognostic variables for PFS, whereas residual disease, PS and post-chemotherapy CA125 (10.8 U/ml as cut-off) were independent prognostic variables for OS.Post-operative CA125 using 10.8 U/ml as cut-off was an independent prognostic variable for both PFS and OS.

Objective : To investigate the prevalence of renal impairment in patients with ovarian cancer at the time of the diagnosis. Study design : Creatinine clearance was estimated according to Cockcroft and Gault (C&G Ccr), glomerular filtration rate (GFR) was determined as renal clearance of 99mTc-DTPA, and renal ultrasound was performed in 60 consecutive patients with newly diagnosed ovarian cancer. Results : A 28% of the total population studied had a GFR 2 . A moderate/severe dilation of the upper urinary tract was found in 12% of patients. The length of kidneys ranged between 9.0 and 13.5cm, and a statistically significant correlation was found between kidney length and values of GFR. Conclusion : A reduction in renal function and a moderate to severe dilation of upper urinary tract frequently occur in patients with ovarian cancer at the time of the diagnosis.

Objectives The purpose of this retrospective study was to assess the clinical outcome of patients with high-risk, early-stage endometrioid endometrial cancer (stage Ib or II with myometrial invasion > 50%, grade 2-3). Methods We assessed 192 patients who underwent hysterectomy, bilateral salpingo-oophorectomy and pelvic lymphadenectomy, had histologically negative pelvic nodes, and had negative CT findings for aortic node involvement. Results Tumor relapsed in 36 patients after a median time of 21.2 months. The recurrence was vaginal in 7 (19.4%), distant in 16 (44.4%), aortic in 8 (22.2%), and involved multiple sites in 5 (13.9%). There was a trend to a lower vaginal recurrence rate in the 143 patients who received adjuvant radiotherapy (+ chemotherapy) compared with the 46 who did not (2.1% versus 8.7%). Distant or aortic recurrences were lower in the 37 patients who received adjuvant chemotherapy (+ radiotherapy) than in the 152 who did not (2.7% versus 18.4%, p = 0.02). Of the 29 patients who received sequential adjuvant chemotherapy and radiotherapy, none developed local recurrence and only one had distant recurrence. There was a trend for a better 5-year progression-free survival and overall survival for the patients who received chemotherapy (+ radiotherapy) compared with those who did not (86.0% versus 71.3%, and 92.3% versus 75.6%, respectively). Conclusions Our data appear to suggest that adjuvant chemotherapy reduces the risk of distant or aortic recurrences and that sequential adjuvant chemotherapy and radiotherapy achieve an excellent local and distant control of disease in these clinical settings. © 2014 Published by Elsevier Inc.

Purpose Neoadjuvant chemotherapy [NACT] followed by radical hysterectomy is an alternative therapeutic option to concurrent chemotherapy-radiotherapy for locally advanced cervical cancer. However there are very few data about the effectiveness of any post-operative treatment in this clinical setting. The purpose of this study was to correlate the patterns of recurrence and the clinical outcomes of cervical cancer patients who received NACT, with postoperative adjuvant treatment. Patients and methods This retrospective multicenter study included 333 patients with FIGO stage Ib2-IIb cervical cancer who underwent platinum-based NACT followed by radical surgery. Pathological responses were retrospectively assessed as complete; optimal partial; and suboptimal response. Overall optimal response rate was the sum of complete and optimal partial response rates. Results On the whole series, recurrence-free survival was significantly longer in patients who achieved an overall optimal response than in those who did not (p < 0.0001), and in patients who received adjuvant chemotherapy compared to those who did not (p = 0.0001). On multivariate analysis, consolidation therapy (p = 0.0012) was the only independent prognostic variable for recurrence-free survival; whereas FIGO stage (p = 0.0169) and consolidation therapy (p = 0.0016) were independent prognostic variables for overall survival. Conclusion Optimal responders after chemo-surgical treatment for FIGO stage Ib2-IIb cervical cancer do not need any further treatment. Additional cycles of chemotherapy could be of benefit for patients with suboptimal response and intra-cervical residual disease. Both adjuvant chemotherapy and adjuvant radiation treatments do not seem to improve the clinical outcome of patients with extra-cervical residual disease compared to no further treatment. © 2014 Elsevier Inc.

Objective. The objective of this retrospective multicenter study was to assess the pattern of failures and survival of patients with primary carcinoma of the fallopian tube. Methods. The hospital records of 88 patients with primary carcinoma of the fallopian tube were reviewed. Surgery was the initial therapy for all patients. Tumor stage was I in 21 (23.9%), II in 21 (23.9%), III in 43 (48.8%), and IV in 3 (3.4%) patients. Postoperative treatment was given without well-defined protocols. The median follow-up of survivors was 55 months (range, 7-182). Results. Of the 21 patients with stage I disease, 10 had no postoperative treatment and 11 had platinum-based chemotherapy. Five (23.8%) patients recurred after a median of 29 months (range, 8-93) from initial surgery. Of the 21 patients with stage II disease, 2 had no postoperative treatment, 2 underwent external pelvic irradiation, 16 received platinum-based chemotherapy, and 1 patient had oral melphalan. Eight (38.1%) patients recurred after a median of 25.5 months (range, 7-57). Of the 46 patients with stage III-IV disease, 1 patient refused chemotherapy and died after 19 months and 45 patients received platinum-based chemotherapy. A clinical complete response was obtained in 29 (64.4%) patients and a partial response in 8 (17.8%). A second-look laparotomy was performed in 14 of the 29 clinically complete responders: 12 patients were found to be in pathological complete response and 2 had persistent disease. Six (50.0%) of the former recurred after a median of 22 months (range, 13-101) from initial surgery. The two patients with persistent disease developed tumor progression after 15 and 11 months, respectively. Fifteen clinically complete responders did not undergo second-look, and 7 (46.7%) of them had a recurrence after a median of 18 months (range, 9-41). For the whole series, 5-year survival was 57%. By log-rank test, survival was related to FIGO stage (III-IV vs I-II, P = 0.0001), tumor grade (G3 vs G1 + G2, P = 0.0038), and patient age (>58.5 years vs

Gadducci A, Ferdeghini M, Cosio S, Fanucchi A, Cristofani R, Genazzani AR. The clinical relevance of serum CYFRA 21-1 assay in patients with ovarian cancer.CYFRA 21-1 assay, which detects serum fragments of cytokeratin 19, has been widely assessed as a serum marker of several malignancies. Preoperative serum CYFRA 21-1 levels were retrospectively measured in 60 patients with ovarian cancer and in 59 control patients with benign ovarian disease. CYFRA 21-1 levels were also serially measured in 90 serum samples drawn from patients with advanced (FIGO stage III-IV) ovarian cancer followed after surgery and chemotherapy. Preoperative serum CYFRA 21-1 levels were higher in patients with ovarian cancer compared with controls (median, range = 2.6, 0.1–51.4 ng/ml versus 0.4, 0.0–3.6 ng/ml, P < 0.0001), and among the former, antigen values were higher in the 39 patients with advanced-stage than in the 21 patients with early (FIGO stage I-II) disease (P < 0.0001). In advanced ovarian cancer patients, the 25%, 50%, and 75% quantiles of preoperative CYFRA 21-1 levels were 1.9, 4.8 and 14.4 ng/ml, respectively. Preoperative CYFRA 21-1 levels were lower in the 11 patients who achieved a pathologic complete response at second-look compared with those who had clinically or surgically detectable persistent disease after first-line chemotherapy (median, range 1.9, 0.6–9.2 ng/ml versus 10.2, 0.1–51.4 ng/ml, P = 0.007). The pathologic complete response rate was significantly greater in patients with low preoperative CYFRA 21-1 levels compared with those with elevated CYFRA 21-1 levels at any cut-off limit for the antigen (1.9, 4.8 and 14.4 ng/ml). However, Cox regression analysis failed to detect a significant association between preoperative CYFRA 21-1 assay and survival. As for the follow-up of advanced ovarian cancer patients, CYFRA 21-1 levels were higher in the 42 samples drawn from patients with clinically detectable disease compared with the 48 specimens collected from patients with no clinical evidence of disease (median, range = 1.15, 0.3–40.7 ng/ml versus 0.4, 0.1–9.1 ng/ml, P < 0.0001). In conclusion, preoperative serum CYFRA 21-1 assay appears to be predictive of response to chemotherapy, but not prognostic of survival, for patients with advanced ovarian cancer. Moreover, the serial measurement of CYFRA 21-1 levels might have a potential clinical relevance for the assessment of disease status in patients followed after surgery and chemotherapy.