Positive p16 Immunostaining Is an Independent Prognostic Variable for Disease-free Survival and Overall Survival in Patients With Squamous Cell Carcinoma of the Vulva Treated With Radical Surgery and Inguinofemoral Lymphadenectomy: An Italian Single Center Retrospective Study.

BACKGROUND/AIM: The expression of the cyclin-dependent kinase inhibitor p16 correlates with the presence of human papillomavirus. The purpose of this investigation was to assess the prognostic relevance of p16 expression in patients with vulvar squamous cell carcinoma (VSCC) treated with radical surgery followed by adjuvant (chemo) radiation in selected cases. PATIENTS AND METHODS: Seventy-eight patients were analyzed retrospectively. RESULTS: Positive p16 immunostaining was detected in 19 (24.4%) patients. Five-year disease-free survival (DFS) and 5-year overall survival (OS) were better in p16-positive compared to p16-negative patients (83.9% versus 37.3% p=0.002 and 91.7% versus 57.6%, p=0.003, respectively). p16 expression retained prognostic relevance at multivariate analysis for both DFS and OS. CONCLUSION: p16 expression was detected in 24.4% of patients with VSCC and was found to be an independent prognostic variable for both DFS and OS.

Perineural Invasion Correlates With Common Pathological Variables and Clinical Outcomes of Patients With Squamous Cell Carcinoma of the Vulva Treated With Primary Radical Surgery and Inguinal-femoral Lymphadenectomy.

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.

A narrative review of pregnancy after malignancies in young women that don't originate in the female genital organs or in the breast.

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.

Positron Emission Tomography/Computed Tomography in Platinum-sensitive Recurrent Ovarian Cancer: A Single-center Italian Study.

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.

Dose individualization can minimize nephrotoxicity due to carboplatin therapy in patients with ovarian cancer.

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.

Lymph-vascular space involvement and outer one-third myometrial invasion are strong predictors of distant haematogeneous failures in patients with stage I-II endometrioid-type endometrial cancer.

The aim of this retrospective study was to assess the predictive value of different clinicopathological variables (patient age, tumour size, FIGO grade, myometrial invasion, lymph-vascular space involvement [LVSI], invasion margins, peri-tumour phlogistic infiltrate and mitotic activity) for the risk of distant haematogenous recurrences in patients with endometrioid-type stage Ib-II endometrial cancer. Between August 1990 and April 2005, 259 patients had undergone laparotomy, peritoneal washing, total abdominal hysterectomy and bilateral salpingo-oophorectomy, with or without pelvic +/- para-aortic lymphadenectomy for endometrioid-type endometrial cancer. Thirty-six (13.9%) patients had developed recurrent disease after a median time of 17 months (range, 2-128 months). The relapse had been locoregional in 9, distant in 21 and both locoregional plus distant in 6 cases. This study assessed 12 patients with FIGO stage Ib-II disease who had developed distant haematogenous recurrences and 20 randomly chosen control patients with FIGO stage Ib-II disease who had remained recurrence-free after a median follow-up of 52 months (range, 37-66 months). Adjuvant therapy had been: no further treatment in 15 patients, external pelvic irradiation in 14 patients, adjuvant external pelvic irradiation plus brachytherapy in 2 patients and platinum-based chemotherapy followed by external pelvic irradiation in 1 patient. The site of distant failure had been the lung in 9 patients, liver in 2 patients and lung plus liver in 1 patient. A concomitant locoregional relapse (vagina or lymph nodes) had occurred in 3 patients. The median interval between surgery and the development of distant failure had been 16.5 months (range, 5-113 months). On univariate analysis, a higher incidence of FIGO grade 3 (50% versus 10%, p=0.0114), outer one-third myometrial invasion (91.7% versus 35.0%, p=0.0051) and LVSI (75.0.% versus 20.0%, p=0.0022) was found in the patients who had developed distant haematogeneous metastases compared to the recurrence-free women. Multivariate analysis showed that LVSI (p=0.0264) and deep myometrial invasion (p=0.0345) were independent predictive variables for the risk of distant haematogeneous failure. Patients with these pathological findings should be enrolled in randomised trials designed to assess the role of adjuvant chemotherapy alone or combined with sequential and/or concomitant external pelvic irradiation.

Molecular target therapies in endometrial cancer: from the basic research to the clinic.

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.

Brain recurrences in patients with ovarian cancer: report of 12 cases and review of the literature.

The aim of the investigation was to assess 12 cases of brain recurrences among ovarian cancer patients who had undergone surgery followed by platinum-based chemotherapy. Brain lesions were the first recurrence in 4 (33%) patients, the second recurrence in 7 (58%), and the fourth recurrence in one patient. The median time from ovarian cancer diagnosis to brain metastasis detection was 33.5 months (range, 13.5-86.5 months), brain metastases were multiple in 6 (50%) cases, and extra-cranial disease was present in 7 (58%) cases. Brain recurrence was symptomatic in 10 patients and the clinical presentation included impaired deambulation, extremity weakness, seizure, headache, nausea/vomiting and visual disturbance. Out of the 6 patients with single brain metastases, one underwent surgery, one had surgical excision followed by whole brain irradiation, 3 patients received stereotactic radiotherapy (followed by chemotherapy for coexistent extra-abdominal recurrence in one), and one had only symptomatic treatment. Out of the 6 patients with multiple brain metastases, four received whole brain irradiation (followed by chemotherapy for concomitant extra-cranial recurrence in one case), one patient had gamma-knife irradiation of three cerebral lesions (followed by chemotherapy for concurrent abdominal recurrence), and one patient had only symptomatic treatment. The median overall survival from diagnosis of brain metastasis was 8.3 months (range, 1-28 months), and it was not related to the number of brain metastases (multiple versus single), presence or absence of extra-cranial disease, or interval between ovarian cancer diagnosis and brain metastasis detection (<33.5 months versus > or =33.5 months). In conclusion, brain metastasis from ovarian cancer can represent a late manifestation of the disease, associated with a very poor prognosis.

Dose-dense Paclitaxel- and Carboplatin-based Neoadjuvant Chemotherapy Followed by Surgery or Concurrent Chemo-radiotherapy in Cervical Cancer: a Preliminary Analysis.

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.

Old and new perspectives in the management of high-risk, locally advanced or recurrent, and metastatic vulvar cancer.

During the last decades there has been a continuing evolution in the surgical approach of squamous cell carcinoma of the vulva that has been traditionally treated with radical vulvectomy and bilateral inguinal-femoral lymphadenectomy. Patients with T1 tumour are usually treated with radical local excision, if the lesion is unifocal and the remainder of the vulva is normal. Patients with T1a disease have no risk of groin metastases and do not need lymphadenectomy, whereas those with T1b disease need ipsilateral inguinal-femoral lymphadenectomy if the lesion is lateral, and bilateral lymphadenectomy if the lesion is midline. Modifications of the surgical technique of deep femoral lymphadenectomy and the mapping of sentinel node can offer new interesting therapeutic perspectives. Postoperative adjuvant pelvic and groin irradiation is warranted for patients with two or more or macroscopically involved groin nodes. Locally advanced squamous cell carcinoma of the vulva has been long surgically treated with en-block radical vulvectomy and bilateral inguinal-femoral lymphadenectomy plus partial resection of urethra, vagina or anum, or by exenteration, with severe postsurgical complications, poor quality of life, and unsatisfactory survival rates. 5-Fluorouracil [5-FU] or 5-FU- and cisplatin-based chemotherapy concurrent with irradiation followed by tailored surgery represents an attractive therapeutic option for advanced disease, planned to avoid such ultra-radical surgical procedures and, hopefully, to improve patient outcome. Chemotherapy has also been used in neoadjuvant setting, with contrasting and generally unsatisfactory results, and in palliative treatment of patients with distant metastases. Surgery is the primary treatment also for vulvar malignancies other than squamous cell carcinoma, whereas the clinical usefulness of adjuvant irradiation or chemotherapy is still to be defined. Primary chemoradiation can be also used for advanced carcinoma of the Bartholin gland or for advanced adenocarcinoma associated with extramammary Paget's disease. The drugs used for chemotherapy of metastatic melanomas or sarcomas of the vulva are the same employed for the melanomas or sarcomas developed in other sites.

Prognosis of Patients with Gestational Trophoblastic Neoplasia and Obstetric Outcomes of Those Conceiving After Chemotherapy.

AIM: To assess prognosis of gestational trophoblastic neoplasia (GTN) and obstetric outcome after chemotherapy. PATIENTS AND METHODS: 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. RESULTS: 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. CONCLUSION: 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.

Neutropenic enterocolitis in an advanced epithelial ovarian cancer patient treated with paclitaxel/platinum-based chemotherapy: a case report and review of the literature.

BACKGROUND: Literature data show that neutropenic enterocolitis is a rare but severe complication that can occur in cancer patients treated with chemotherapy and especially with taxanes. CASE REPORT: A 60-year-old woman with stage Illc epithelial ovarian cancer developed neutropenic fever, abdominal pain, severe diarrhoea, nausea, vomiting and oral mucositis one week after the first postoperative cycle of paclitaxel (175 mg/m2 3-hour infusion) plus carboplatin-based chemotherapy. Abdominal X-ray showed diffuse dilatation of the ileal and colonic loops with air/fluid. The patient soon recovered after intensive supportive care. For the second cycle the dose of paclitaxel was reduced by 20%, but nine days later the patient again developed severe neutropenia with fever, abdominal colicky pain, diarrhoea and vomiting. The culture of blood samples collected on admission was found to be positive for Escherichia coli, whereas stools resulted negative for both enteric rods and Clostridium difficile toxin. The patient recovered with intensive supportive care, and chemotherapy was continued with single-agent carboplatin. DISCUSSION: The increasing use of paclitaxel in first-line as well as in the salvage treatment of epithelial ovarian cancer could increase the occurrence of neutropenic enterocolitis in patients with this malignancy. The importance of symptoms such as neutropenic fever, abdominal pain and tenderness and severe diarrhoea should be stressed in patients who receive taxane-based chemotherapy, and intensive supportive care management should be started immediately.

Chemotherapy with epirubicin and paclitaxel for breast cancer during pregnancy: case report and review of the literature.

BACKGROUND: Breast cancer diagnosed during pregnancy is a challenging clinical situation. Little data are currently available about chemotherapy in pregnant women with this malignancy. CASE REPORT: We report the case of a 36-year-old pregnant woman with a T2N1M0 breast cancer who received sequential chemotherapy including epirubicin (120 mg/m2 every three weeks for four cycles) and paclitaxel (175 mg/m2 every three weeks for three cycles) from the 14th to the 32nd week of gestation. The patient delivered a normal female baby by caesarean section at the 36th week. The immunohistochemical examination of the placenta showed a diffuse, strong P-glycoprotein expression. Thirty-six months after the delivery, the mother was disease-free and the infant showed normal development and growth. DISCUSSION: Sequential chemotherapy including epirubicin and paclitaxel should be taken into consideration as adjuvant treatment for pregnant women with high-risk breast cancer. The strong placental expression of P-glycoprotein may play a major role in limiting fetal exposure to anthracyclines and taxanes.

Intratumoral microvessel density, response to chemotherapy and clinical outcome of patients with advanced ovarian carcinoma.

BACKGROUND: The aim of this study was to assess intratumoral microvessel density (IMD) in tissue samples from primary ovarian carcinomas, and to correlate this angiogenic parameter with the common clinico-pathological variables, response to chemotherapy and prognosis of patients with this malignancy. PATIENTS AND METHODS: The investigation was conducted on 64 patients who underwent initial surgery for FIGO stages I-IV ovarian carcinoma. Paraffin-embedded sections of primary tumor specimens were analyzed for IMD by immunohistochemistry using anti-CD34 antibodies. In detail, we assessed the 49 patients with advanced (FIGO stages II-IV) disease. Postoperative chemotherapy consisted of paclitaxel/platinum-based chemotherapy in 36 (73.5%) patients and platinum-based chemotherapy in 13. RESULTS: The IMD ranged from 6 to 115 microvessels/field, with a median value of 40, and correlated with none of the common clinico-pathological variables of ovarian carcinoma. As for the patients with advanced disease, women with elevated IMD (> or = 40 microvessels/field) had a higher chance of achieving a complete response to chemotherapy when compared to those with lower IMD (p = 0.0068). Multiple logistic regression showed that IMD was an independent predictor of complete response to chemotherapy (p = 0.0094). By log-rank test, patients with elevated IMD had a better progression-free survival (p = 0.0039) and a better overall survival (p = 0.0365) when compared to those with lower IMD. The Cox model showed that IMD was the only independent prognostic variable for both progression-free survival (p = 0.0112) and overall survival (p = 0.0296). DISCUSSION: The present retrospective analysis seems to show a positive association between IMD, response to chemotherapy, mainly represented by a paclitaxel/platinum-based regimen, and clinical outcome of patients with advanced ovarian carcinoma.

Vascular endothelial growth factor (VEGF) expression in primary tumors and peritoneal metastases from patients with advanced ovarian carcinoma.

BACKGROUND: Several experimental and clinical data suggest that vascular endothelial growth factor (VEGF) is involved in ovarian carcinogenesis. However, there are no conclusive data about the prognostic value of tissue VEGF expression in this malignancy. The aim of the present investigation was to compare VEGF immunostaining in primary tumors and peritoneal metastases from patients with advanced ovarian carcinoma and to assess whether this parameter has a predictive or prognostic relevance. MATERIALS AND METHODS: The investigation was conducted on 45 patients who underwent initial surgery followed by platinum-based or paclitaxel/platinum-based chemotherapy for advanced ovarian carcinoma. Both primary tumors and peritoneal metastases were immunohistochemically analyzed for VEGF expression. Intense staining score was assigned if more than 75% of the cells stained positive. RESULTS: Intense VEGF immunostaining was detected in 14 and 36 (31.1% versus 80.0%, p < 0.0001), respectively, of primary tumors and peritoneal metastases. Twenty-six (57.8%) patients showed an increased VEGF immunostaining in metastatic lesions compared with primary tumors. VEGF immunostaining in primary tumors, VEGF immunostaining in peritoneal metastases and change in VEGF immunostaining from the primary tumor to peritoneal metastatic lesion were related neither to the response to chemotherapy nor to progression-free survival. CONCLUSION: In patients with advanced ovarian carcinoma, intense VEGF immunostaining was more often detected in peritoneal metastases than in primary tumors. VEGF immunostaining in primary as well as in metastatic lesions correlated neither with the response to chemotherapy nor with the clinical outcome. Therefore the immunohistochemical detection of VEGF in tissue samples collected during primary surgery failed to have a predictive or prognostic relevance for patients with advanced ovarian carcinoma.

Patterns of failures in endometrial cancer: clinicopathological variables predictive of the risk of local, distant and retroperitoneal failure.

UNLABELLED: The aim of this study was to assess the pattern of failure and the outcome of endometrial cancer patients and to analyze the variables predictive of the risk of local, distant and retroperitoneal lymph node disease recurrence. PATIENTS AND METHODS: The authors assessed 511 patients who underwent primary surgery. The median follow-up of survivors was 74 months. Peritoneal, hematogenous and lymph node recurrences outside retroperitoneal area were considered as distant failures. RESULTS: Tumor relapsed in 83 (16.2%) patients. Median time to recurrence was 18.5 months (range, 3-129 months). The relapse was local in 13 cases, distant in 37, retroperitoneal in 22, and involved both distant and other sites in 11. Logistic regression showed that cervical involvement was the only independent predictor of local recurrence. Tumor grade, lymph-vascular space involvement (LVSI) and myometrial invasion were independent predictors of distant failure. Lymph node status and tumor grade were independent predictors of retroperitoneal recurrence. Five- and 10-year overall survival rates were 87.1% and 79.5%, respectively. Patient age, lymph node status, cervical involvement, tumor grade, LVSI and myometrial invasion were independent prognostic variables for overall survival. CONCLUSION: Cervical involvement was an independent predictor of local recurrence, LVSI and myometrial invasion were independent predictors of distant failure, lymph node status was an independent predictor of retroperitoneal relapse, and tumor grade was an independent predictor of both distant and retroperitoneal recurrence. The identification of risk factors for different patterns of failure can be useful in better tailoring adjuvant treatment.

Clinicopathological variables predictive of clinical outcome in patients with FIGO stage Ib2-IIb cervical cancer treated with cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy.

The aim of this retrospective investigation was to assess the prognostic relevance of some pre-treatment clinical variables and histological findings assessed on the surgical samples of 46 patients with stage Ib(2)-IIb cervical cancer treated with cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy. Seven patients achieved a pathologically documented complete response, 6 had an optimal partial response, 29 had a suboptimal partial response, and 4 had stable disease. As for histological findings on surgical samples, 7 (15.2%) patients had positive lymph nodes, 10 (21.7%) had lymph-vascular space involvement, and 10 (21.7%) had positive parametria and/ or surgical margins. After surgery, 38 patients received further treatment with chemotherapy and/or irradiation. The median follow-up of survivors was 53 months (range, 4-167 months).Thirteen (28.3%) patients developed recurrent tumour, 11 (23.9%) patients died of tumour and one patient died of ictus with no clinical evidence of tumour. Recurrence-free and overall survival were significantly related to tumour stage (Ib(2)-IIa versus IIb, p=0.01 and p=0.02, respectively), pathologically assessed lymph node status (negative versus positive, p=0.0009 and p=0.007), lymph-vascular space status (negative versus positive, p=0.01 and p=0.009), parametrial and/or surgical margin status (negative versus positive, p=0.0001 and p=0.0005), but not to haemoglobin level before chemotherapy, patient age, tumour grade or chemotherapy regimen. A platelet count before chemotherapy above the median value of 272,000/microl was associated with a trend for a shorter recurrence-free survival (p=0.06) and with a significantly shorter overall survival (p=0.04) when compared with a lower platelet count. In conclusion, FIGO stage, lymph node status, lymph-vascular space status, parametrial and/or surgical margin status and pre-treatment platelet count are predictors of clinical outcome in patients with FIGO stage Ib(2)-IIb cervical cancer undergoing cisplatin-based neoadjuvant chemotherapy followed by radical hysterectomy. A multivariate analysis on a larger series of homogeneously treated patients is warranted to better define the clinicopathological risk factors useful to adequately plan the therapeutic strategy.

Pattern of failures and clinical outcome of patients with locally advanced cervical cancer treated with a tailored integrated therapeutic approach.

AIM: To review a tailored treatment with concurrent chemoradiotherapy (CT/RT) or neoadjuvant chemotherapy (NACT) followed by radical hysterectomy in locally advanced cervical cancer. PATIENTS AND METHODS: One hundred and four patients were treated with a tailored therapeutic approach. CT/RT was the standard treatment for patients with stage Ib2-IIb disease aged more than 70 years, or with high surgical risk, as well as for those with stage III-IV disease. NACT followed by radical hysterectomy was the treatment of choice for patients with stage Ib(2)-IIb disease, maximum age of 70 years and good performance status. RESULTS: For the 61 women who underwent CT/RT, 5-year disease-free (DFS) survival and 5-year overall survival (OS) were 62% and 71%, respectively. Patient outcome was associated with the clinical response to CT/RT (complete responders versus others: 5-year DFS, 81% versus 19%, p<0.001; 5-year OS, 84% versus 37%, p=0.001). For the 43 women who underwent NACT, 5-year DFS and 5-year OS were 66% and 75%, respectively. Patient outcome was associated with the pathological response to chemotherapy (optimal responders versus others: 5-year DFS, 89% versus 62%, p=0.03; 5-year OS, 90% versus 72%, p=0.05). CONCLUSION: Tailored treatments obtained satisfactory clinical outcomes in locally advanced cervical cancer. Optimal pathological response to NACT has been found to be a surrogate endpoint of OS. The identification of biological variables able to predict response to NACT is strongly warranted for an accurate selection of patients who may really benefit from chemosurgical treatment.

Biochemical prognostic factors and risk of relapses in patients with cervical cancer.

No validated tumor marker is currently available for the management of patients with cervical cancer. However, some tumor-associated antigens have been measured in the sera from patients with this malignancy and have been related to the clinical course of disease. Squamous cell carcinoma antigen (SCC) is more sensitive than CYFRA 21-1 for squamous cell cervical cancer. Serum SCC levels are elevated in 28-88% of patients with this malignancy, and correlate with tumor stage, tumor size, cervical stromal invasion, lymph-vascular space involvement, and lymph node status. Some authors reported that pre-treatment serum SCC has no prognostic value, whereas others found that it is related to disease-free survival and/or overall survival at univariate analysis or at multivariate analysis. Serial SCC measurements correlate with tumor response to radiotherapy and/or chemotherapy and the clinical outcome of patients. Increasing serum SCC can precede the clinical diagnosis of relapse in 46-92% of cases, with a median lead time ranging from 2 to 8 months. According to some authors serum SCC assay during the follow-up does not improve the cure rate of patients who will ultimately develop a recurrence. However, it has been recently reported that the performance of a PET in asymptomatic patients with serum SCC elevation can sometimes allow an earlier diagnosis of relapse with a survival benefit. Serum CA 125 levels are raised in 20-75% of patients with cervical adenocarcinoma, and reflect tumor stage, tumor size, histological grade, cervical stromal invasion, lymph-vascular space involvement, and lymph node status. Pre-treatment CA 125 levels appear to have a prognostic value, and rising serum CA 125 may precede or be coincident with the clinical diagnosis of recurrent cervical adenocarcinoma.

Polycystic ovary syndrome and gynecological cancers: is there a link?

Polycystic ovary syndrome [PCOS] is the most common endocrinopathy of women in reproductive age. An association between PCOS and type-1 endometrial cancer has often been reported in the literature. The prolonged anovulation with consequent continued secretion of estrogen unopposed by progesterone may enhance the development and growth of this malignancy, particularly in young women. Hypersecretion of luteinizing hormone [LH], chronic hyperinsulinemia and increased serum insulin-like growth factor [IGF]-I levels may represent risk factors for endometrial cancer. However, data available in the literature do not allow a meta-analysis to be carried out to calculate an estimate of the relative risk of endometrial cancer in women with PCOS. Anecdotal cases of low-grade endometrial stromal sarcoma and carcinosarcoma have been reported in association with prolonged unopposed estrogen stimulation, and in particular with PCOS. A few studies have addressed the possibility of an association between PCOS and epithelial ovarian cancer risk, and the results are conflicting but generally reassuring, and similarly the few available data appear to exclude a strong association between PCOS and breast cancer.