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OBJECTIVE: To evaluate the prognostic impact of routinely use of staging laparoscopy (S-LPS) in patients with primary advanced epithelial ovarian cancer (AEOC). METHODS: All women were submitted to S-LPS before receiving primary debulking surgery (PDS) or neoadjuvant treatment (NACT). The surgical and survival outcome were evaluated by univariate and multivariate analysis. RESULTS: Among 300 consecutive patients submitted to S-LPS no complications related to the surgical procedure were registered. The laparoscopic evaluation showed that almost half of the patients (46.3%) had a high tumor load. One-hundred forty-eight (49.3%) women were considered suitable for PDS and the remaining 152 (50.7%) were submitted to NACT. The percentages of complete (residual tumor, RT=0) and optimal (RT<1cm) cytoreduction of PDS and interval debulking surgery (IDS) were 62.1% and 57.5%, 22.5% and 27.7%, respectively, p=0.07. The post-operative complications of NACT/IDS group were lower than PDS group (p=0.01). The median progression free survival in women with RT=0 at PDS was 25 months (95% CI, 15.1-34.8), which was statistically significant longer than in all other patients, irrespective of the type of treatment they received (p=0.0001). At multivariate analysis, residual disease (p=0.011) and performance status (p=0.016) maintained an independent association with the PFS. CONCLUSIONS: Including S-LPS in a tertiary referral center for the management AEOC does not appear to have a negative impact in terms of survival and it may be helpful to individualize the treatment avoiding unnecessary laparotomies and surgical complications.

OBJECTIVE: We evaluated the rates of response, operability and long term survival and toxicities in a large series of locally advanced cervical cancer (LACC) patients administered neoadjuvant chemotherapy (NACT) with paclitaxel, epirubicin and cisplatin (TEP) followed by radical surgery (RS). Patients and methods The study included 75 consecutive stages IB2-IVA patients administered NACT with paclitaxel (175mg/m(2)), epirubicin (100mg/m(2)) and cisplatin (100mg/m(2)) on day 1 of a 3-weekly cycle for 2-4cycles. Patients were evaluated for objective response by RECIST criteria and triaged to RS. Progression-free survival (PFS) and overall survival (OS) were calculated from the date of diagnosis to recurrence/progression of disease or death, respectively. RESULTS: Complete and partial clinical response was observed in 13 and 28 patients (56.1% objective responses); radical surgery was amenable in 52 patients (71.2%): 14 patients showed complete/microscopic response to treatment. Overall, recurrence/progression of disease was observed in 36 patients, and all of them experienced death of disease. In the whole series median PFS was 48months (5-year PFS=51.0%), and median OS was 72months (5-year OS=53.0%). Overall, 195 courses were administered; treatment was delayed in 6.7% of patients, while dose reduction was required in 36.5% of patients. Grade 3 leukopenia affected 22 patients (29.7%), while Grades 3 and 4 neutropenia was documented in 17 (22.9%) and 6 (8.1%) patients. In the whole series, we recorded 1 death whose relation with treatment-induced toxicity could not be ruled out. CONCLUSIONS: TEP provided favorable rates of response and operability in LACC patients, and allowed the obtainment of encouraging survival data without carrying out an excessive toxicity.

BACKGROUND: A long-term prospective assessment of QoL in cervical cancer patients is still lacking. Here, we provide the first 2-years prospective, longitudinal study evaluating emotional distress and QoL in early stage (ECC) and locally advanced (LACC) cervical cancer patients who remained disease-free 2-years from diagnosis. METHODS: The questionnaires: Hospital Anxiety and Depression Scale (HADS), Global Health Status items of EORTC QLQ-C30 (GHS), and EORTC QLQ-CX24 (CX24) have been administered by a dedicated team of psycho-oncologists, administered at baseline, and after 3, 6, 12 and 24 months from surgery The Generalized Linear Model for repeated measure was used to analyze modifications of QoL measures over time. RESULTS: In both groups, an early reduction of the percentage of patients with anxiety levels ≥11 was observed at the 3-month evaluation (ECC: 25.7% at baseline Vs 14.7% after 3 months, p value=0.001; LACC: 22.2% at baseline Vs 15.4% after 3 months, p value=0.001). Despite this favorable trend, after 2 years from diagnosis, 11.9% of ECC and 15.6% of LACC patients still showed an anxiety score ≥11. No significant changes over time were observed in term of Depression levels. Focusing on QoL issues, mean GHS and Sexual Activity scores showed an improvement over time in both groups compared to baseline (GHS: 5.7% difference for ECC, p value=0.001, and 11.0% in LACC, p value=0.001; SXA: 13.9% difference for ECC, p value=0.001; and 6.1% in LACC, p value=0.008). On the other hand, Body Image mean scores were significantly impaired by chemoradiation administration in LACC patients, without long-term recovery (7.5% difference, p value=0.001). Finally, in both groups, lymphedema (LY) and menopausal symptoms (MS) showed an early worsening which persisted 2-year after surgery (LY: 19.5% difference for ECC, p value=0.014, and 27.3% in LACC, p value=0.001; MS: 14.4% difference for ECC, p value=0.004, and 16.0% in LACC, p value=0.002). CONCLUSIONS: Despite a signif

OBJECTIVE: This prospective study aimed at analyzing the ability of ultrasound to evaluate the extension of the disease and to predict the likelihood of suboptimal cytoreduction in advanced ovarian cancer patients. METHODS: 147 patients with advanced ovarian cancer were consecutively enrolled. All patients underwent standard laparotomy, and maximal surgical effort was attempted. The sonographic parameters used to set up scoring system predicting suboptimal cytoreduction were: peritoneal carcinomatosis, bowel mesentery involvement, omental involvement, massive pelvic involvement, ascites, liver and/or spleen metastases. Sonographic parameters achieving a negative predictive value>50%, and a positive predictive value>50% in predicting suboptimal cytoreduction were included in the ultrasound score. RESULTS: Ultrasound offered a virtually conclusive diagnosis of massive pelvic involvement (sensitivity = 94%, specificity = 97%), parenchymal liver metastases any size (sensitivity = 93%, specificity = 98%) and ascites (sensitivity = 98%, specificity = 97%); a very reliable diagnosis of peritoneal carcinomatosis (sensitivity = 91%, specificity = 88%) and omental involvement (sensitivity = 94%, specificity = 90%), whereas it was not very good at excluding parenchymal spleen metastases or splenic hilus involvement (sensitivity = 75%, specificity= 98%) and bowel mesentery involvement (sensitivity= 67%, specificity = 88%). Ultrasound-assessed peritoneal carcinomatosis, bowel mesentery involvement, omental involvement, massive pelvic involvement and ascites were included in the ultrasound score (range from 0 to 6). With the selected cut-off value (>5), the sensitivity and specificity with regard to suboptimal cytoreduction of the ultrasound score were 31% (20/64) and 92% (46/50)". CONCLUSIONS: Ultrasound examination is able to assess intra-abdominal disease in advanced ovarian cancer with a satisfying concordance with laparotomic findings. Our ultrasound score can predict subopt

Non-puerperal uterine inversion due to uterine sarcomas represents a very rare event with no reliable estimate of frequency in the literature. Clinically, the diagnosis of inversion may be difficult, as far as imaging procedures are concerned, although ultrasonography may prove to be useful. However, some characteristics such as the indentation of the fundic area and a depressed longitudinal groove extending from the uterus to the center of the inverted portion are difficult to recognize. Moreover, there is no specific computed tomography feature accurate enough to aid in the differential diagnosis. Here, we report a case of uterine inversion due to Müllerian uterine adenosarcoma whose preoperative workup and diagnosis took advantage of the application of magnetic resonance imaging.

Madelung's disease or multiple symmetric lipomatosis (MSL) is a rare disorder of unknown etiology which typically presents symmetrically subcutaneous accumulation of non-encapsulated adipose tissue which slowly grows around the neck, upper part of the arms, pelvis, back and thigh. This disease is also frequently associated with hepatopathy, glucose intolerance, hyperuricemia, and malignant tumors of the upper airways. Nevertheless, only one description of malignant transformation of Madelung's disease has been presented in literature. Here, we report a case of liposarcomatous transformation of Madelung's disease in a 59-year-old Italian woman with a coincidental diagnosis of breast cancer. VIRTUAL SLIDE: The virtual slide for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/3480884087499351.

Stromal elements within a tumor interact with cancer cells to create a microenvironment that supports tumor growth and survival. Adrenomedullin (ADM) is an autocrine/paracrine factor produced by both stromal cells and cancer cells to create such a microenvironment. During differentiation of macrophages, ADM is produced in response to pro-inflammatory stimuli and hypoxia. In this study we investigated the role of ADM as a growth factor for ovarian cancer cells and as a modulator of macrophages. We also analyzed ADM expression levels in a retrospective clinical study using nanofluidic technology and assessment of ADM at the gene level in 220 ovarian cancer patients. To study the effects of ADM, ovarian cancer cell lines A2780, OVCAR-3, and HEY and their drug-resistant counterparts were used for proliferation assays, while monocytes from healthy donors were differentiated in vitro. ADM was a weak growth factor, as revealed by proliferation assays and cell cycle analysis. After culturing cancer cells under stressing conditions, such as serum starvation and/or hypoxia, ADM was found to be a survival factor in HEY but not in other cell lines. In macrophages, ADM showed activity on proliferation/differentiation, primarily in type 2 macrophages (M2). Unexpectedly, the clinical study revealed that high expression of ADM was linked to positive outcome and to cancer with low Ca125. In conclusion, although in vitro ADM was a potential factor in biological aggressiveness, this possibility was not confirmed in patients. Therefore, use of an ADM antagonist would be inappropriate in managing ovarian cancer patients.

OBJECTIVE:To report the Phase II study final results in terms of pathological complete response (pCR) and complications in locally advanced cervical carcinoma (LACC) patients treated with chemoradiation (CT/RT) regimen based on accelerated fractionation, nodal extended fields and adjuvant radical surgery. METHODS: The sample size was quantified according to published data which shows that CT/RT followed by radical surgery in LACC patients provides a pCR rate above 45%. The 2-stage design by Simon was used to test the null hypothesis that the true pCR would improve by above 20%. The chemoradiation regimen was considered active if >24/43 pCRs were recorded. 40 Gy/2 Gy fraction in 4 weeks was delivered to nodal volume extending up to L3 vertebra, concurrently with chemotherapy. 45 Gy in 20 fractions with a concomitant boost strategy was delivered to the macroscopic disease only. RESULTS: 47 patients were enrolled. Median follow-up was 26 months (3-52 months). Pathological response was assessed in 44/47 patients: 17/44 (38.6%) showed a pCR to treatment, and 9/44 cases (20.5%) showed microscopic disease. Pelvic nodal metastases were documented in 9/44 cases (20.5%). 87.5% of recurrences were extra pelvic. Five patients (11%) developed acute severe gastrointestinal toxicity. The actuarial cumulative 2-year incidence of G ≥ 2 late cutaneous, gastrointestinal, and genitourinary toxicity was 10.3%, 8.3% and 24.9%, respectively. The 3-year DFS was 77.1%, while the 3-year OS was 80.5%. CONCLUSIONS: Our results confirm the high tolerability and efficacy of this accelerated regimen. However, based on the study design, 45 Gy as a concomitant boost CT/RT delivered by a 3D technique does not seem sufficient to increase pCR rate.

BACKGROUND: The goal of this study was to prospectively analyze the diagnostic performances of magnetic resonance imaging (MRI) and positron emission tomography (PET)/computed tomography (CT) in predicting pathologically assessed residual disease in a large, single-institution series of locally advanced cervical cancer (LACC) patients triaged to neoadjuvant treatments followed by radical surgery. METHODS: Between April 2007 and March 2010, 96 patients with histologically documented cervical cancer (any histology) and FIGO stage IB2-IVA were enrolled. MRI and PET/CT were recommended to be performed within 4-6 weeks from the end of treatment, and histology was the reference standard. Sensitivity, specificity, and accuracy were compared using the McNemar test. RESULTS: For residual disease in the cervix, sensitivity was higher for MRI than for PET/CT (86.1% vs 63.1%; P = .002), while specificity was significantly higher for PET/CT compared with MRI (P = .002). There was no difference in accuracy values between the 2 imaging modalities. For MRI analysis of lymph node groups, sensitivity, specificity, and accuracy were 35.7%, 95.9%, and 88.0%, respectively. Conversely, sensitivity, specificity, and accuracy for PET/CT were 28.6%, 97.8%, and 88.7%, respectively. Absence of follicular structures replaced by prevalent sclerosis and/or sinus histiocytosis was the most frequently documented morphological pattern in false-positive cases. CONCLUSION: Neither MRI nor PET/CT accurately detected residual disease in LACC patients triaged to radical surgery after neoadjuvant treatment, disallowing the option of avoiding or modulating completion surgery.

This prospective, longitudinal study investigates QoL issues and emotional distress in early stage cervical cancer (ECC) patients undergoing radical surgery (RS) and in locally advanced cervical cancer (LACC) patients triaged to chemoradiation (CT/RT) followed by RS.

PURPOSE: To define the maximum tolerated dose of a conformal short-course accelerated radiotherapy in patients with symptomatic advanced pelvic cancer. METHODS AND MATERIALS: A phase I trial in 3 dose-escalation steps was designed: 14 Gy (3.5-Gy fractions), 16 Gy (4-Gy fractions), and 18 Gy (4.5-Gy fractions). The eligibility criteria included locally advanced and/or metastatic pelvic cancer and Eastern Cooperative Oncology Group performance status of ≤3. Treatment was delivered in 2 days with twice-daily fractionation and at least an 8-hour interval. Patients were treated in cohorts of 6-12 to define the maximum tolerated dose. The dose-limiting toxicity was defined as any acute toxicity of grade 3 or greater, using the Radiation Therapy Oncology Group scale. Pain was recorded using a visual analog scale. The effect on quality of life was evaluated according to Cancer Linear Analog Scale (CLAS). RESULTS: Of the 27 enrolled patients, 11 were male and 16 were female, with a median age of 72 years (range 47-86). The primary tumor sites were gynecologic (48%), colorectal (33.5%), and genitourinary (18.5%). The most frequent baseline symptoms were bleeding (48%) and pain (33%). Only grade 1-2 acute toxicities were recorded. No patients experienced dose-limiting toxicity. With a median follow-up time of 6 months (range 3-28), no late toxicities were observed. The overall (complete plus partial) symptom remission was 88.9% (95% confidence interval 66.0%-97.8%). Five patients (41.7%) had complete pain relief, and six (50%) showed >30% visual analog scale reduction. The overall response rate for pain was 91.67% (95% confidence interval 52.4%-99.9%). CONCLUSIONS: Conformal short course radiotherapy in twice-daily fractions for 2 consecutive days was well tolerated up to a total dose of 18 Gy. A phase II study is ongoing to confirm the efficacy on symptom control and quality of life indexes.

Objective: The aim of this study was to evaluate the role of bilateral mammography undertaken before adjuvant radiotherapy in patients with conservatively managed invasive carcinoma of the breast.Methods: Patients with invasive breast cancer referred to the Radiotherapy Department of the Catholic University in Campobasso, Italy, between March 2002 and September 2006 were retrospectively reviewed. Patients were referred to our facility from other local and regional hospitals where they received breast-conserving surgery and adjuvant chemotherapy. They presented to our department for post-operative whole-breast radiotherapy. All patients underwent physical examination and bilateral mammography prior to adjuvant irradiation.Results: 201 patients met the selection criteria as delineated. Of these 201 patients who underwent pre-radiotherapy mammography, 3 had suspicious findings on mammography. In 2 of those cases, the histopathological examination confirmed the presence of residual disease within the residual mammary gland. In one case, the pre-radiotherapy mammogram allowed for the detection of disease persistence which was not otherwise appreciated on physical exam. In the other case, the diagnostic imaging confirmed only the findings of the physical exam. In both cases of residual disease, the tumour was found elsewhere in the breast and not at the primary site. In one patient, the radiological re-assessment led to a false-positive result. No cases of contralateral synchronous breast cancer were observed. The overall adjunctive cost of this strategy including a routine mammography besides the clinical visit was €7012 for all patients.Conclusions: No clear recommendation exists regarding post-operative mammography before adjuvant radiotherapy. In our experience, this strategy allowed for the detection of gross disease persistence after surgery which was not appreciated at clinical examination in 1 case out of 201. In this patient, adjuvant radiotherapy up to a total d

A phase I-II prospective clinical trial of adjuvant accelerated radiation therapy (ADA-RT-1 trial) was set up in order to investigate the feasibility and efficacy of a pelvic conformal radiotherapy technique with concomitant boost (CB technique) to the vaginal vault in high-risk uterine cancers.

The purpose was to compare the dosimetric results observed in 201 breast cancer patients submitted to tangential forward intensity-modulated radiation therapy (IMRT) with those observed in 131 patients treated with a standard wedged 3D technique for postoperative treatment of whole breast, according to breast size and supraclavicular node irradiation. Following dosimetric parameters were used for the comparison: D(max), D(min), D(mean), V(95%) and V(107%) for the irradiated volume; D(max), D(mean), V(80%) and V(95%) for the ipsilateral lung; D(max), D(mean), V(80%) and V(95%) for the heart. Stratification was made according to breast size and supraclavicular (SCV) nodal irradiation. As respect to irradiated volume, a significant reduction of V(107%) (mean values: 7.0 ± 6.6 versus 2.4 ± 3.7, p < 0.001) and D(max) (mean % values: 111.2 ± 2.7 versus 107.7 ± 6.3, p < 0.001), and an increase of D(min) (mean % values: 65.0 ± 17.4 versus 74.9 ± 12.9, p < 0.001) were observed with forward IMRT. The homogeneity of dose distribution to target volume significantly improved with forward IMRT in all patient groups, irrespective of breast size or supraclavicular nodal irradiation. When patients treated with supraclavicular nodal irradiation were excluded from the analysis, forward IMRT slightly reduced V(80%) (mean values: 3.7 ± 2.6 versus 3.0 ± 2.4, p = 0.03) and V(95%) (mean values 1.9 ± 1.8 versus 1.2%± 1.5; p = 0.001) of the ipsilateral lung. The dose to the heart tended to be lower with IMRT but this difference was not statistically significant. Tangential forward IMRT in postoperative treatment of whole breast improved dosimetric parameters in terms of homogeneity of dose distribution to the target in a large sample of patients, independent of breast size or supraclavicular nodal irradiation. Lung irradiation was slightly reduced in patients not undergoing to supraclavicular irradiation.

We describe successful operative management of a solitary breast cancer metastasis in the chest wall after complete response with concomitant non-pegylated liposomal doxorubicin (NPLD) and docetaxel followed by sternal rib resection with prosthetic reconstruction. We report a case of a 41-year-old woman who had a breast cancer recurrence infiltrating neighboring osteo-cartilage of the left sternal body, the cartilaginous portion of the third and fourth ipsilateral ribs and was inseparable from the rear side pectoral reaching deep into contiguity with the pericardium. After 6 cycles of chemotherapy with NPLD plus docetaxel, sternal rib resection with prosthetic reconstruction was performed. Histological examination did not show any evidence of residual tumor. At 9 months of follow-up, the patient appears free of disease. Our case demonstrates that a multimodal approach in patients with chest wall recurrence of breast cancer without distant metastasis, may be safe and effective for maintaining a good quality of life.

The purpose was to compare the dosimetric results observed in 201 breast cancer patients submitted to tangential forward intensity-modulated radiation therapy (IMRT) with those observed in 131 patients treated with a standard wedged 3D technique for postoperative treatment of whole breast, according to breast size and supraclavicular node irradiation. Following dosimetric parameters were used for the comparison: D(max), D(min), D(mean), V(95%) and V(107%) for the irradiated volume; D(max), D(mean), V(80%) and V(95%) for the ipsilateral lung; D(max), D(mean), V(80%) and V(95%) for the heart. Stratification was made according to breast size and supraclavicular (SCV) nodal irradiation. As respect to irradiated volume, a significant reduction of V(107%) (mean values: 7.0 ± 6.6 versus 2.4 ± 3.7, p < 0.001) and D(max) (mean % values: 111.2 ± 2.7 versus 107.7 ± 6.3, p < 0.001), and an increase of D(min) (mean % values: 65.0 ± 17.4 versus 74.9 ± 12.9, p < 0.001) were observed with forward IMRT. The homogeneity of dose distribution to target volume significantly improved with forward IMRT in all patient groups, irrespective of breast size or supraclavicular nodal irradiation. When patients treated with supraclavicular nodal irradiation were excluded from the analysis, forward IMRT slightly reduced V(80%) (mean values: 3.7 ± 2.6 versus 3.0 ± 2.4, p = 0.03) and V(95%) (mean values 1.9 ± 1.8 versus 1.2%± 1.5; p = 0.001) of the ipsilateral lung. The dose to the heart tended to be lower with IMRT but this difference was not statistically significant. Tangential forward IMRT in postoperative treatment of whole breast improved dosimetric parameters in terms of homogeneity of dose distribution to the target in a large sample of patients, independent of breast size or supraclavicular nodal irradiation. Lung irradiation was slightly reduced in patients not undergoing to supraclavicular irradiation.

OBJECTIVES: To analyze in advanced ovarian cancer patients the ability of ultrasound to evaluate the extent of intra-abdominal disease and to predict the likelihood of suboptimal cytoreduction. METHODS: Into this prospective study, 147 patients with advanced ovarian cancer were enrolled consecutively between January 2005 and October 2008. All patients underwent standard laparotomy and maximal surgical effort was attempted. To create a new scoring system to predict suboptimal cytoreduction we considered the following sonographic parameters: peritoneal carcinomatosis, bowel mesentery involvement, omental involvement, massive pelvic involvement, ascites and liver and/or spleen metastases. Those parameters achieving a negative predictive value ≥ 50% and a positive predictive value ≥ 50% in predicting suboptimal cytoreduction were included in the ultrasound scoring system, which was then calculated for each patient. RESULTS: Ultrasound allowed a virtually conclusive diagnosis of massive pelvic involvement (sensitivity, 94%; specificity, 97%), parenchymal liver metastases of any size (sensitivity, 93%; specificity, 98%) and ascites (sensitivity, 98%; specificity, 97%) and a very reliable diagnosis of peritoneal carcinomatosis (sensitivity, 91%; specificity, 88%) and omental involvement (sensitivity, 94%; specificity, 90%), whereas it was not very good at excluding parenchymal spleen metastases or splenic hilum involvement (sensitivity, 75%; specificity, 98%) and bowel mesentery involvement (sensitivity, 67%; specificity, 88%). Ultrasound-assessed peritoneal carcinomatosis, bowel mesentery involvement, omental involvement, massive pelvic involvement and ascites were included in our ultrasound score (which had a range of 0-6 points). With a cut-off value of > 5, the sensitivity and specificity of the ultrasound score with regard to prediction of suboptimal cytoreduction were 31% (20/64) and 92% (46/50), respectively. CONCLUSIONS: Ultrasound examination is able to assess int

Minimal deviation adenocarcinoma (MDA) is a very rare variant of cervical adenocarcinoma. This pathological entity is composed of mucinous very-well-differentiated glands deeply invading cervical stroma, and often surrounded by a desmoplastic reaction. Despite its benign histological appearance, MDA is typically characterized by aggressive clinical behavior and by relevant difficulties in achieving a final diagnosis. Moreover, the intrinsic chemotherapy resistance, as well as the frequent failure of radiotherapy approaches has raised the need to investigate the efficacy of multimodal strategies for the treatment of MDA patients. Here, we report a case of locally advanced MDA of the uterine cervix in a very young woman, who was successfully treated with concomitant chemoradiation followed by radical surgery.

Cyclooxygenase-2 overexpression is associated with poor outcome and resistance to platinum-based chemotherapy in ovarian cancer. We evaluated the antitumor activity and safety of the combination carboplatin plus the COX-2 inhibitor celecoxib in recurrent heavily-treated OC patients.

We describe successful operative management of a solitary breast cancer metastasis in the chest wall after complete response with concomitant non-pegylated liposomal doxorubicin (NPLD) and docetaxel followed by sternal rib resection with prosthetic reconstruction. We report a case of a 41-year-old woman who had a breast cancer recurrence infiltrating neighboring osteo-cartilage of the left sternal body, the cartilaginous portion of the third and fourth ipsilateral ribs and was inseparable from the rear side pectoral reaching deep into contiguity with the pericardium. After 6 cycles of chemotherapy with NPLD plus docetaxel, sternal rib resection with prosthetic reconstruction was performed. Histological examination did not show any evidence of residual tumor. At 9 months of follow-up, the patient appears free of disease. Our case demonstrates that a multimodal approach in patients with chest wall recurrence of breast cancer without distant metastasis, may be safe and effective for maintaining a good quality of life.

The economic evaluation of any human papillomavirus (HPV) vaccination strategy requires the measurement of clinical benefits (quality-adjusted life-years [QALY]) gained to reflect both the increase in life expectancy and the economic benefits associated with an effective intervention.

Carboplatin/paclitaxel is the standard first-line chemotherapy for patients with advanced ovarian cancer. Multicentre Italian Trials in Ovarian Cancer-2 (MITO-2), an academic multicenter phase III trial, tested whether carboplatin/pegylated liposomal doxorubicin (PLD) was more effective than standard chemotherapy.

AIMS: The study aimed at describing the prevalence, and pattern of comorbidities, as well as their clinical role in a large series of locally advanced cervical cancer (LACC) patients triaged to preoperative chemoradiation. METHODS: The Charlson index (CCI), and the ACE27 index were used to retrospectively evaluate comorbidities in 258 LACC patients: life tables were computed by the Kaplan-Meier method; multivariate analysis was performed by Cox's regression model. RESULTS: A CCI score = 0 was documented in 225 patients (87.2%), while 24 patients (9.3%) had a CCI score = 1, and only 9 patients (3.5%) had a CCI score ≥ 2. An ACE27 score = 0 was documented in 170 patients (65.9%), and was 1 in 59 patients (22.8%), 2 in 24 patients (9.3%) and 3 in 5 patients (2%). There was no association between the presence of comorbidities and clinico-pathological variables with the exception of a direct association with older age. There was no difference in the distribution of comorbid cases according to the extent of hysterectomy and lymphadenectomy. DFS or OS curves did not differ in patients with or without comorbidities according to both indexes. No difference in the distribution of patients with comorbidities according to presence of complications was documented. CONCLUSIONS: The role of comorbidities in the decision-making process relative to the enrollment of LACC patients into this trimodal therapeutic strategy needs to be established in specifically designed prospective trials

OBJECTIVES: To determine the agreement between ultrasonographic and histological examination of the cervix in patients with early stage cervical cancer with regard to tumor size and local extent of the disease. METHODS: Eighteen patients with histologically proven cervical cancer stage IB1-IIA according to traditional clinical staging (FIGO 1988) and scheduled for radical surgery underwent a standardized transvaginal ultrasound examination: the maximum tumor length, anterior-posterior tumor diameter, tumor width, tumor area, depth of cervical stroma invasion, and the minimal thickness of tumor free cervical stroma on sagittal and transverse planes through the cervix were measured, and the local extent of the disease into the parametria and vagina was evaluated. The surgical specimens were examined using a dedicated method of histopathological examination. The results of the ultrasound and histopathological examinations were compared. RESULTS: Limits of agreement were wide and the Inter-Class Correlation Coefficient (Inter-CC) was low (0.51 to 0.58) for three of the four measurements taken to represent the minimal depth of tumor free cervical stroma, i.e. the results for the measurements taken posteriorly and laterally. The limits of agreement were smaller and the Inter-CC values were higher (0.74 - 0.92) for the depth of cervical stroma invasion and for the tumor size measurements. Histological examination revealed parametrial cancer infiltration in four patients. All these cases were detected at ultrasound examination with no false positive results.

The supply of oxygen and nutrients to solid tumors is inefficient because cancer tissues have an inadequate number of microvessels, thus inducing the selective growth of the most aggressive cancer cells. This explains why many of the factors underlying a poor prognosis are induced in hypoxic/hypoglycemic conditions. Among these factors, a prominent role in several solid tumors is played by the class III beta-tubulin gene (TUBB3). The study described here reveals that glucose deprivation enhances TUBB3 expression at both the gene and protein levels in A2780 ovarian cancer cells. In silico analysis of TUBB3 mRNA sequence predicted a putative binding site for the RNA-binding protein Hu antigen (HuR) in the 3' flanking untranslated region. A hypoglycemic-dependent engagement of this site was shown using RNA pull-down and ribonucleoimmunoprecipitation techniques. Thereafter, HuR gene silencing revealed that TUBB3 translation is HuR dependent in hypoglycemia because HuR silencing inhibited the entry of TUBB3 mRNA into cytoskeletal and free polysomes. Finally, the clinical value of this finding was assessed in a clinical cohort of 46 ovarian cancer patients in whom it was found that HuR cytoplasmic staining was associated with high levels of TUBB3 and poor survival

The full clinical relevance of the expression pattern of HER family of type I receptor tyrosine kinases in laryngeal squamous cell carcinoma remains to be elucidated. We evaluated the clinical relevance of such parameter in our population.

Primary: To investigate whether S-LPS could contribute to a better identification of patients to submit to IDS. Secondary: To identify the most appropriate level of laparoscopic index value (PIV) to identify inoperable patients in this subset of patients.

BACKGROUND: We report the first case of isolated pancreatic lymph node recurrence in a locally advanced breast cancer patient. CASE: A 41-year old woman underwent radical mastectomy according to Madden and removal of axillary lymph nodes for multicentric infiltrating ductal carcinoma pathologically staged as pT2N2M0. After six years from primary diagnosis, and four years from the diagnosis of lung recurrence, she developed an isolated metastatic lesion to pancreatic lymph node. After surgical excision of metastasis, hormone therapy with Exemestane was begun. At 16 months of follow-up, the patient appears free of disease. CONCLUSION: Because metastatization to visceral organ carries a very unfavorable prognosis, we think that the clinical significance of the elevation of CA 15.3 serum levels in the early detection of recurrence and in monitoring metastatic disease during follow-up, should be not underestimated.

A longitudinal, retrospective, cohort study was designed to assess the mean treatment cost of invasive cervical cancer, cross-linking clinical and administrative databases. The study was performed from the Italian NHS perspective. Costs were estimated using DRG charges. All patients with histological diagnosis of invasive cervical cancer admitted to Gynecologic Oncology centres of the Catholic University of the Sacred Heart between 2000 and 2007 were enrolled.

The objective of the study was to estimate the antitumor activity of pemetrexed in patients with advanced/recurrent carcinoma of the cervix and to determine the nature and degree of toxicity.

OBJECTIVE: Preoperative chemoradiation (CT/RT) has been shown to achieve encouraging results in terms of clinical outcome in locally advanced cervical cancer (LACC). The study aims at analyzing the long-term results of this multimodal approach in a single institution series of 184 cases. METHODS: Patients underwent whole pelvic irradiation combined with cisplatin and 5-fluorouracil. After evaluation of clinical response, patients were triaged to surgery. Surgical morbidity was classified according to Chassagne grading system. Univariate and multivariate analyses were used to assess the prognostic and predictive role of clinicopathological parameters. RESULTS: Clinical response was observed in 96.1% of cases. A total of 174 cases were submitted to radical surgery: 124 patients (71.3%) showed complete/microscopic pathological response. In multivariate analysis, clinical response, stage of disease, and histotype predicted response to CT/RT. With a median follow-up of 58 months, recurrence and death of disease were observed in 42 and 40 patients, respectively. The 5-year DFS was 75.5%, while the 5-year OS was 77.4%. Patients with no residual disease showed a significant longer DFS than patients with microscopic (p value = 0.0128), and macroscopic (p value = 0.0001) residual tumor after treatment. In multivariate analysis, residual tumor and stage of disease were the two most relevant prognostic factors for DFS and OS. As far as long-term toxicity is concerned, 8 out of 22 complications were grade 3/4. CONCLUSION: Preoperative CT/RT is worth further investigation in LACC patients, providing encouraging survival outcomes and a favourable long-term toxicity profile.

To determine the maximum tolerated dose of short-course radiotherapy (intensity-modulated radiotherapy technique) to the upper two thirds of the vagina in endometrial cancers with low risk of local recurrence. PATIENTS AND METHODS: A Phase I clinical trial was performed. Eligible patients had low-risk resected primary endometrial adenocarcinomas. Radiotherapy was delivered in 5 fractions over 1 week. The planning target volume was the clinical target volume plus 5 mm. The clinical target volume was defined as the upper two thirds of the vagina as evidenced at CT simulation by a vaginal radio-opaque device. The planning target volume was irradiated by a seven-field intensity-modulated radiotherapy technique, planned by the Plato Sunrise inverse planning system. A first cohort of 6 patients received 25 Gy (5-Gy fractions), and a subsequent cohort received 30 Gy (6-Gy fractions). The Common Toxicity Criteria scale, version 3.0, was used to score toxicity. RESULTS: Twelve patients with endometrial cancer were enrolled. Median age was 58 years (range, 49-74 years). Pathologic stage was IB (83.3%) and IC (16.7%). Median tumor size was 30 mm (range, 15-50 mm). All patients completed the prescribed radiotherapy. No patient experienced a dose-limiting toxicity at the first level, and the radiotherapy dose was escalated from 25 to 30 Gy. No patients at the second dose level experienced dose-limiting toxicity. The most common Grade 2 toxicity was gastrointestinal, which was tolerable and manageable. CONCLUSIONS: The maximum tolerated dose of short-course radiotherapy was 30 Gy at 6 Gy per fraction. On the basis of this result, we are conducting a Phase II study with radiotherapy delivered at 30 Gy.

The malignant transformation of endometriosis is a very uncommon event but can occur in 0.7% to 1% of all cases. Any histological type of tumor found in the endometrium might also occur in endometriosis. Most malignant tumors that originate from endometriosis are endometrioid adenocarcinomas and also clear-cell type carcinomas. On the other hand, sarcomas, especially endometrial stromal sarcoma (ESS), are extremely unusual representing 12% of all cases. ESS is an uncommon neoplasm and accounts for 0.2% of the uterine malignances. Malignant tumors arising from endometriosis can derive from the uterine wall as well as from extra-uterine sites. The most frequent extrauterine location is the ovary (78.7%), followed by the pelvic peritoneum (5.7%), the rectovaginal septum (4.3%), the colon (4.3%) and the vagina (2%), representing the majority of extragonadal sites. ESSs arising from the extrauterine and extraovarian endometriosis sites in the absence of a primary uterine lesion are extremely rare and the treatment options are not clear. Surgical debulking seems to be the best treatment. Adjuvant therapy, such as radiation, hormonal therapy and chemotherapy are not yet proven to be effective. Molecular target therapy could be a future possibility of treatment. A systematic review of English Medical Literature about incidence, treatment and prognosis of extrauterine ESS arising from endometriosis foci was performed. The selected articles on which this review is based are the following: 9 literature reviews, 8 retrospective studies, 7 case series, 1 prospective trial and 11 case reports.

Background: Varied deformities of the upper arm are common after massive weight loss. Brachioplasty techniques have been successively modified to improve aesthetic outcomes and avoid complications, especially lymphedema and sensory damage. Objectives: The authors evaluated lymphatic drainage and sensory function of the upper limbs after brachioplasty performed with a double-ellipse marking technique, a medial incision, superficial undermining, and posterior arm liposuction. Methods: This prospective study included 12 women who underwent brachioplasty after bariatric surgery and massive weight loss. Lymphatic drainage was evaluated by forearm volumetry and indocyanine green lymphography of the entire limb. Cutaneous sensitivity thresholds were determined with Semmes-Weinstein monofilaments. Results: Patients received postoperative follow up for 12 months. Complications included a small dehiscence for 1 patient and hypertrophic scarring for 2 patients. Cutaneous sensitivity and forearm volumetry were unchanged after brachioplasty for all patients. Results of indocyanine green lymphography indicated that all patients had normal linear lymphatic patterns pre- and postoperatively. Conclusions: Results of the study support the belief that this type of brachioplasty does not disrupt sensory or lymphatic function of the limb.

Introduction To identify a subset of cervical cancer (CC) patients administered chemoradiation (CT/RT) plus radical surgery (RS), who can be spared lymphadenectomy, and complications. Patients and methods 430 Stage IB2-IIB patients without LN involvement at imaging were accrued (March 1996–December 2015) at Gynecologic Oncology Unit of the Catholic University of Rome/Campobasso. CT/RT consisted of pelvic irradiation plus cisplatin based chemotherapy. Objective response was evaluated according to RECIST criteria; radical hysterectomy and pelvic ± aortic lymphadenectomy was attempted in patients achieving response or stable disease. Surgical morbidity was classified according to the Chassagne grading system. Results 421 cases underwent RS; metastatic pelvic and aortic LNs were documented in 10.7%, and 8.8% of cases, respectively. In patients without residual tumor in the cervix, there was only 1 case (0.53%) with positive pelvic LNs, and 1 case (2.3%) with metastatic aortic LNs. Analysis of patients according to pre- and post-CT/RT imaging was able to select cases without any metastatic LNs: in patients with negative pelvic LNs at pre- and post-CT/RT imaging, none of cases without residual disease in the cervix had metastatic pelvic or aortic LNs. Of 149 early complications, 76 (51.0%) were lymphovascular. The most frequent late complications were lymphovascular (N = 25/61, 41.0%). Conclusion Lymphadenectomy could be avoided in stage IB2-IIB CC patients undergoing preoperative CT/RT, when a careful evaluation of pre- and post-CT/RT imaging and histological assessment of no residual disease in the cervix is made. This approach may avoid lymphadenectomy in 40% of patients with a favourable impact on lymphovascular morbidity.

Along with their role in the maintenance of nuclear architecture, nuclear lamins also control genomic stability, DNA damage repair, transcription, cell proliferation, differentiation and senescence. Recent reports reveal that prelamin A-processing defects play a role in cancer development by impacting on transcription of key players in the maintenance of the genome stability, including RAD51. Here, we performed a 'proof of concept' study evaluating the role of prelamin A and RAD51 expression in clinical outcome of cervical cancer patients. We analyzed biomarker expression by immunohistochemistry in tumor material from locally advanced cervical cancer (LACC) patients (n=66) and correlated data with clinicopathological parameters and with response to neoadjuvant chemoradiation (CT/RT). In LACC patients who underwent neoadjuvant CT/RT the percentage of cases showing high prelamin A levels was greater in patients who completely responded to treatment (25 of 40, 62.5%) than in patients with macroscopic residual tumor (6 of 26, 23.1%, p=0.0024). Conversely, patients showing high RAD51 expression were less likely to respond to treatment (14 of 26, 53.8%) than were those with low protein levels (12 of 40, 30%, p=0.072). Only prelamin A retained an independent role in predicting response to treatment (p=0.003), while RAD51 approached statistical significance (p=0.07). Notably, high RAD51 expression highly significantly predicted poor outcome, emerging as an independent prognostic factor for disease free survival (p=0.038), while approaching statistical significance for overall survival (p=0.09). Our findings provide a framework for future prospective studies investigating molecular predictors of response to neoadjuvant chemoradiotherapy in LACC patients.

INTRODUCTION: Optimal management of recurrent ovarian cancer (ROC) remains an area of uncertainty. An estimated 85% of patients with epithelial ovarian cancer who achieve a full remission following first-line therapy will develop recurrent disease and median survival for these patients' ranges from 12Â months to 24Â months. Many patients receive several lines of treatment following recurrence and, although each subsequent line of therapy is characterized by shorter disease-free intervals, decisions about the most appropriate treatment is complex. Areas covered: This review focuses on chemotherapy, surgery and emerging biologic agents that present a therapeutic option for patients with ROC. Expert commentary: Recurrent ovarian cancer is not curable. The goals of therapy should focus on palliation of cancer-related symptoms, extension of life, and maintenance of quality of life. Patients with platinum-sensitive ovarian cancer should have their recurrence treated with a platinum-based agent. For patients whose cancer progresses after platinum retreatment and for those with platinum-resistant disease, numerous other non-platinum combination and targeted therapies have been shown to be effective in palliating cancer-related symptoms and extending life.

Purpose Platinum-based chemotherapy (PBC) for patients with progressing ovarian cancer (OC) is more effective with a longer time interval from previous platinum treatment (platinum-free interval [PFI]). In 1999, it was hypothesized that prolonging PFI with single-agent non-PBC (NPBC) may offer a strategy to improve overall outcome. MITO-8 aimed to verify this hypothesis commonly used in clinical practice although it has not been prospectively tested. Methods MITO-8 is an open-label, prospective, randomized, superiority trial. Patients with OC who experienced disease progression 6 to 12 months after their last platinum treatment were randomly assigned 1:1 to the experimental sequence of NPBC followed by PBC at subsequent relapse or the standard reverse treatment sequence. Overall survival (OS) was the primary end point. Results Two hundred fifteen patients were enrolled (standard arm [n = 108]; experimental arm [n = 107]). The trial ended before planned because of slow enrollment. PFI was prolonged in the experimental arm(median, 7.8 v 0.01 months). Therewas no OS benefit in the experimental arm(median, 21.8 v 24.5 months; hazard ratio, 1.38; 95% CI, 0.99 to 1.94; P = .06). Progression-free survival after the sequence was significantly shorter in the experimental arm (median, 12.8 v 16.4 months; hazard ratio, 1.41; 95% CI, 1.04 to 1.92; P = .025). Global quality-of-life change after three cycles was worse in the experimental arm. Slight differences were observed in the incidence of adverse effects. Conclusion MITO-8 supports the recommendation that PBC not be delayed in favor of an NPBC in patients with partially platinum-sensitive OC. PBC should be used as a control arm in future trials of new drugs in this setting.

Study Objective: To analyze the feasibility and safety of laparoscopic secondary cytoreductive surgery in a retrospective series of patients with platinum-sensitive recurrent ovarian cancer. Design: Retrospective cohort study (Canadian Task Force classification II-2). Setting: Catholic University of the Sacred Heart, Rome, Italy. Patients: Between October 2010 and October 2016, 58 patients with recurrent ovarian cancer were selected for a retrospective analysis of data. Interventions: All patients underwent a laparoscopic secondary cytoreduction with single or multiple procedures. Results: The most frequent pattern of recurrence was peritoneal (48.3%); 6 patients (10.3%) experienced parenchymal disease (spleen, n = 5; liver, n = 1), and 24 patients (41.4%) had lymph node recurrence. Complete debulking was achieved in all patients. The median operative time was 204 minutes (range, 55-448 minutes), median estimated blood loss was 70 mL (range, 20-300 mL), and the median length of hospital stay was 4 days (range, 1-21 days). Four patients (6.8%) experienced intraoperative complications. Early postoperative complications were documented in 6 patients (10.3%), but only 1 G3 complication was noted. The median duration of follow-up since secondary cytoreduction was 24 months (range, 9-71 months). Twenty-one patients (36.2%) experienced a second disease relapse. The median progression-free survival (PFS) was 28 months, and the 2-year PFS was 58.7%. Five patients died (8.6%); the 2-year overall survival was 90.7%. Conclusions: For selected patients, laparoscopy is a feasible and safe approach to optimal cytoreduction for patients with recurrent ovarian cancer.

This article discusses the current use of volumetric modulated arc therapy (VMAT) techniques in clinical practice and reviews the available data from clinical outcome studies in different clinical settings. An overview of available literature about clinical outcomes with VMAT stereotactic/radiosurgical treatment is also reported. Materials and methods: All published manuscripts reporting the use of VMAT in a clinical setting from 2009 to November 2016 were identified. The search was carried out in December 2016 using the National Library of Medicine (PubMed/Medline). The following words were searched: â volumetric arc therapyâ [All Fields] OR â vmatâ [All Fields] OR â rapidarcâ [All Fields], AND â radiotherapyâ [All Fields] AND â Clinical Trialâ [All Fields]. Results: Overall, 37 studies (21 prospective and 16 retrospective) fulfilling inclusion criteria and thus included in the review evaluated 2,029 patients treated with VMAT; of these patients, ~30.8% had genitourinary (GU) tumors (81% prostate, 19% endometrial), 26.2% head-and-neck cancer (H&NC), 13.9% oligometastases, 11.2% had anorectal cancer, 10.6% thoracic neoplasms (81% breast, 19% lung), and 7.0% brain metastases (BMs). Six different clinical scenarios for VMAT use were identified: 1) BMs, 2) H&NC, 3) thoracic neoplasms, 4) GU cancer, 5) anorectal tumor, and 6) stereotactic body radiation therapy (SBRT) performed by VMAT technique in the oligometastatic patient setting. Conclusion: The literature addressing the clinical appropriateness of VMAT is scarce. Current literature suggests that VMAT, especially when used as simultaneous integrated boost or SBRT strategy, is an effective safe modality for all cancer types.

Background: The study aimed too investigate the rate of hepatoceliac lymph node (HCLN) involvement, as well as its association with clinicopathologic features, together with morbidity of HCLN resection and the prognostic impact of metastatic HCLN status on patients with advanced ovarian cancer (OC) undergoing cytoreductive surgery. Methods: All consecutive patients with stages 3c to 4 epithelial OC who underwent HCLN surgery from January 2010 to September 2016 were analyzed for surgical procedures, pathology, and oncologic outcomes. Results: During the study period, 85 patients underwent HCLN resection. Absence of visible tumor at the end of surgery was documented for 73 of the patients (85.9%). The median number of HCLNs removed was 6 (range 1–18). Histopathologic evaluation was able to identify HCLN metastasis in 45 (52.9%) of the 85 cases. No difference in the rate of surgical morbidity according to pathologic status of HCLN was observed. As of December 2016, the median follow-up period was 36 months (range 6–54 months). Recurrence of disease was observed in 35 (41.2%) of the 85 cases. Relapse of disease most frequently occurred for the patients with metastatic HCLN involvement (65.7%) compared with the patients who had no HCLN involvement (34.3%) (p = 0.048). The median progression-free survival values were 16 months (95% confidence interval [CI], 12–19 months) for the patients with metastatic HCLNs and 22 months (95% CI, 12–19 months) for the patients with no HCLN involvement (p = 0.035). Conclusions: The study confirmed that HCLN surgery is feasible with acceptable morbidities for patients with advanced OC. Metastatic HCLNs are a marker of disease severity associated with worst oncologic outcome.

Background and Objective: There is no available evidence to recommend gonadotropin-releasing hormone (GnRH) analogue-based ovarian suppression versus bilateral salpingo-oophorectomy (BSO) in the adjuvant treatment of early breast cancer, since the two approaches are considered equivalent in terms of oncologic outcome. The role of surgical ovarian ablation has been revitalized based on the advances of minimally invasive surgery, and a better understanding of clinical and molecular basis of hereditary breast/ovarian cancer syndromes. The aim of this study is to analyze the cost-effectiveness of laparoscopic BSO and GnRH analogue administration in patients aged 40–49 years with hormone-sensitive breast cancer. Methods: A probabilistic decision tree model was developed to evaluate costs and outcomes of ovarian ablation through laparoscopic BSO, or ovarian suppression through monthly injections of GnRH analogue. Results were expressed as incremental costs per quality-adjusted life years (QALYs) gained. Results: Laparoscopic BSO strategy was associated with a lower mean total cost per patient than GnRH treatment, and considering the difference in terms of QALYs, the incremental effectiveness did not demonstrate a notable difference between the two approaches. From the National Health Service perspective, and for a time horizon of 5 years, laparoscopic BSO was the dominant option compared to GnRH treatment; laparoscopic BSO was less expensive than GnRH, €2385 [95% confidence interval (CI) = 2044, 2753] vs €7093 (95% CI = 3409, 12,105), respectively, and more effective. Conclusion: Surgical ovarian ablation is more cost-effective than GnRH administration in the adjuvant treatment of hormone-sensitive breast cancer patients aged 40–49 years, and the advantage of preventing ovarian cancer through laparoscopic BSO should be considered.

Background Trabectedin (T) plus pegylated liposomal doxorubicin (PLD) is approved for treatment of platinum-sensitive recurrent ovarian cancer (ROC). Despite the recommendations and guidelines, variations in managing T/PLD administration in routine clinical practice cannot be excluded. We aimed at setting up an Italian survey collecting data about management of T/PLD administration in ROC patients. Methods We carried out the development of a questionnaire-based survey on routine clinical practice in the management of ROC patients administered T/PLD. The survey registered the physicians' approach to modification/discontinuation of treatment, type of modifications, reasons why, and so on. The survey was transmitted to medical oncologists and gynecologic oncologists practicing in national centers/institutions. Results Fifty-eight Italian centers/institutions returned the compiled questionnaire; participants practiced at community cancer centers or hospitals (56.9%), academic institutions (36.2%), and other settings (private clinics, etc) (6.9%). There was no statistically significant difference in the distribution of practice setting according to geographic areas. Most responders were medical oncologists (84.5%) and were members (82.8%) of at least 1 scientific society or cooperative group. Almost 31.5% of responders reported interruption of the whole treatment, mostly because of toxicity (41.2%), followed by patients' choice (29.4%), or achievement of clinical benefit (23.5%). Dose reduction was referred by 47.4% of responders. Reduction of dose for both drugs was referred by 88.5% of responders, and the extent of dose reduction ranged between 10% and 30%. Conclusions This survey highlights the gaps in transposing evidence-based or consensus guidelines in the real-world management of T/PLD administration; these findings could be useful in order to focus the attention on specific knowledge and/or experience gaps and plan pertinent educational programs.

Objective Low-grade serous ovarian carcinomas (LGSOCs) are a histological subtype of epithelial ovarian tumors, accounting for fewer than 5% of all cases of ovarian carcinoma. Due to the chemoresistant nature of this subtype a search for more effective systemic therapies is actively ongoing, hormonal therapy showing some degree of activity in this clinical setting. The present study ought to investigate the hormone receptor status of LGSOCs, as a strategy to provide molecular support for patient-tailored hormonal treatments. Methods Estrogen receptor α (ERα), ERÎ2 isoforms (i.e. ERÎ21, ERÎ22 and ERÎ25), progesterone and androgen receptor (PR, AR) expression was evaluated by immunohistochemistry in 25 untreated LGSOC primary tumors, 6 matched metastases and 6 micropapillary variant of serous borderline tumors (micropapillary SBOTs). In vitro cellular models were used to provide insights into clinical observations. Results Our results showed prominent expression of nuclear ERα, ERÎ22, ERÎ25 and PR in LGSOC primary tissues, while metastatic lesions also exhibit considerable cytoplasmic ERÎ22 levels. Notably, a higher expression of ERÎ21 protein was determined in micropapillary SBOTs compared to LGSOCs. In vitro experiments on LGSOC cell lines (i.e. HOC-7 and VOA-1056) revealed low/absent ERα, PR and AR protein expression, whereas the three ERÎ2 isoforms were all present. Proliferation of HOC-7 and VOA-1056 was not modulated by either the endogenous or the selective synthetic ligands. Conclusions These novel findings highlight the need of assessing relative levels of ERα and ERÎ2 isoforms in the total receptor pool in future clinical studies investigating molecular predictors of response to hormonal therapy in LGSOC.

Background Few data are available on the outcome of surgery after a bevacizumab-containing regimen. The MITO 16A- MaNGO OV2A phase 4 trial evaluates the outcomes of first-line CPB in a clinical-practice-like setting. Here we present the results of the subgroup of patients undergoing IDS after neoadjuvant treatment or suboptimal primary surgery. Methods 400 chemonaà ̄ve epithelial ovarian cancer patients, age ≥ 18, ECOG PS 0–2 were eligible to receive C (AUC 5 d1, q21) plus P (175 mg/m2d1, q21) and B (15 mg/kg d1 q21) for 6 cycles followed by B maintenance until cycle 22nd. Results 79 patients (20%) underwent IDS. Overall, 74 patients received at least one administration of B before IDS. Median age was 61.2, 70% of the patients had FIGO IIIC disease. The median number of cycles before IDS was 3 both for chemotherapy and bevacizumab respectively. A residual disease ≤ 1 cm was achieved in 64 patients (86.5%). Four percent of the patients experienced fever and 4% required blood transfusion after surgery. Surgical wound infection and/or dehiscence, pelvic abscess, intestinal sub-occlusion and fistula were experienced by one patient each. Conclusions In the MITO16A-MaNGO OV2A phase 4 trial, combined chemotherapy and bevacizumab did not hamper IDS and the rate of perioperative complications was similar to what expected without bevacizumab. These data support the hypothesis that adding bevacizumab to first line chemotherapy for ovarian cancer might not be denied to patients for whom IDS is planned.

Background: Sentinel lymph node (SLN) biopsy has emerged as one of the most appreciated techniques for reducing the rate of complete lymph node dissection (LND) performed in patients with early-stage cervical cancer (ECC). However, its performances are still a matter of debate and, to improve them, international guidelines recommend performing at least unilateral LND in case of SLN mapping. In a prior study, we identified a group of patients without evidence of lymph node metastasis (LNM). Our objective is to define a precise risk of LNM for each ECC patient in order to significantly tailor surgery for ECC. Methods: Clinical and pathological data of ECC patients were retrospectively collected by eight Italian institutions. Chi-square test or Fisher’s exact test along with logistic regression analysis was used to determine the association of each variable between patients with or without LNM. Results of logistic regression have been used as a basis to calculate the probability to harboring LNM. Results: A total of 463 ECC patients were identified. No LNM was detected among the 161 (34.8%) patients who met the criteria and were defined as Very Low Risk. In the other 302 patients, the precise risk of LNM was calculated, and it was <1% in 31 (10.3%) patients. Conclusions: Defining the precise risk of LNM could lead to proper selection of patients in whom any lymph nodal procedure, including SLN, could be avoided.

To demonstrate the efficacy and feasibility of preoperative chemoradiation followed by radical surgery in a consecutive series of patients with stage IIIB cervical cancer. METHODS: Between October 1997 and July 2007, 39 patients with International Federation of Gynecology and Obstetrics stage IIIB cervical cancer were consecutively staged and treated at the Catholic University of Rome and Campobasso and at the National Cancer Institute of Milan. Radical surgery was performed 5 to 6 weeks after the end of the cisplatinum-based neoadjuvant chemoradiation. RESULTS: Clinical responses were observed in 35 patients (92.1%): 6 (15.8%) complete and 29 (76.3.8%) partial. Radical surgery was performed in 35 patients (89.7%). According to Chassagne classification, we observed 7 (20.0%) grade 3, 17 (48.6%) grade 2, and 28 (80%) grade 1 surgical complications. At pathological examination, 12 patients (34.3%) showed complete response, 7 patients (20.0%) had only a microscopic disease, 8 patients (22.8%) had a partial response, and the last 8 patients (22.8%) had no change in disease. We registered 11 (31.4%) operative and 4 (11.4%) early postoperative complications. Median follow-up was 33 months (range, 3-80 months). The percentages of 3-year disease-free survival and overall survival were 67.6% and 70.0%, respectively. Patients with complete response and microscopic disease showed better prognosis than patients with partial response and no change (3-year disease-free survival, 100% vs 31%; and 3-year overall survival, 100% vs 39%). CONCLUSIONS: Chemoradiation followed by radical hysterectomy could be administered in patients with stage IIIB cervical cancer with an acceptable rate of complications and with a survival outcome similar to that of chemoradiotherapy, allowing the assessment of pathological response with its implication on clinical outcomes.