Long-term significance of urinary neopterin in ovarian cancer: a study by the Austrian Association for Gynecologic Oncology (AGO).

BACKGROUND: Neopterin is produced by activated macrophages upon stimulation with interferon-γ (IFN-γ) and thus, elevated neopterin concentrations in patients indicate cellular inate immune response. Most studies in patients with malignant diseases found an association between higher neopterin concentrations and reduced survival and impaired prognosis. Nevertheless, neopterin is not a classical tumor marker since it is not produced by the cancer cells themselves. PATIENTS AND METHODS: In a study conducted by the Austrian Gynecologic Oncology Group (AGO) in 114 patients with ovarian cystadenomas and 223 patients with invasive ovarian cancer, patients' urinary neopterin was determined before and after primary therapy. The relevance of neopterin in long-term median follow-up was assessed. RESULTS: Elevated levels (cut-off 250 µmol/mol creatinine) were found less frequently in women with benign ovarian cystadenomas (24%) than in patients with malignant disease (58%). After 10 years, only 57% of ovarian cancer patients with elevated urinary neopterin levels survived without disease progression following primary therapy when compared with 86% of women with normal levels (P < 0.001). Along with residual tumor, FIGO stage, age and histological type, neopterin was significantly associated with overall survival (OS) and progression-free survival (PFS). The median PFS was 52 and 12 months and the median OS was 81 and 24 months for patients with normal and elevated neopterin, respectively, P < 0.001. In a multivariate Cox regression analysis, only residual tumor, neopterin and age were independently associated with OS, while only residual tumor was predictive for PFS. Thirty patients with early-stage invasive ovarian cancer (FIGO I and II) were analyzed separately. Of 3 patients with elevated neopterin, 2 died of disease in contrast to 2 out of 27 patients with normal neopterin (P = 0.004). CONCLUSION: In ovarian cancer, the negative impact of elevated urinary neopterin levels indicates a detrimental effect of cancer-associated inflammatory reaction.

CA-125 can be part of the tumour evaluation criteria in ovarian cancer trials: experience of the GCIG CALYPSO trial.

BACKGROUND: CA-125 as a tumour progression criterion in relapsing ovarian cancer (ROC) trials remains controversial. CALYPSO is a large randomised trial incorporating CA-125 (GCIG criteria) and symptomatic deterioration in addition to Response Evaluation Criteria in Solid Tumours (RECIST) criteria (radiological) to determine progression. METHODS: In all, 976 patients with platinum-sensitive ROC were randomised to carboplatin-paclitaxel (C-P) or carboplatin-pegylated liposomal doxorubicin (C-PLD). CT-scan and CA-125 were performed every 3 months until progression. RESULTS: In all, 832 patients (85%) progressed, with 60% experiencing a first radiological progression, 10% symptomatic progression, and 28% CA-125 progression without evidence of radiological or symptomatic progression. The benefit of C-PLD vs C-P in progression-free survival was not influenced by type of first progression (hazard ratio 0.85 (95% confidence interval (CI): 0.66-1.10) and 0.84 (95% CI: 0.72-0.98) for CA-125 and RECIST, respectively). In patients with CA-125 first progression who subsequently progressed radiologically, a delay of 2.3 months was observed between the two progression types. After CA-125 first progression, median time to new treatment was 2.0 months. In all, 81%of the patients with CA-125 or radiological first progression and 60% with symptomatic first progression received subsequent treatment. CONCLUSION: CA-125 and radiological tests performed similarly in determining progression with C-PLD or C-P. Additional follow-up with CA-125 measurements was not associated with overtreatment.

Combined PEG liposomal doxorubicin and gemcitabine are active and have acceptable toxicity in patients with platinum-refractory and -resistant ovarian cancer after previous platinum-taxane therapy: a phase II Austrian AGO study.

OBJECTIVES: Platinum resistance is a significant problem in patients with ovarian cancer. The aim of this phase II study was to define the response rates, the progression-free survival and the toxicity profile of the combination of PEG liposomal doxorubicin (L-DXR) and gemcitabine (GEM). MATERIAL AND METHODS: Thirty one patients with histologically confirmed platinum-refractory or -resistant epithelial ovarian cancer were scheduled to receive 6 cycles of L-DXR 30 mg/m(2) on day 1 as well as GEM 650 mg/m(2) on days 1 and 8 every 28 days. RESULTS: The median number of chemotherapy cycles given was 4. The mean dose intensity for L-DXR and GEM on day 1 was 96% and 97%, respectively. The mean dose intensity for GEM on day 8 was 93%. The overall response rate was 33% (10 of 30 evaluable patients; 20% complete responses). The median progression-free survival was 3.8 months, and the median overall survival was 15.8 months, respectively. Toxicity was acceptable. One quarter of patients developed grade 3 or 4 neutropenia, but none developed febrile neutropenia. Palmoplantar erythrodysesthesia (PPE) grades 2 and 3 occurred in 13% and 3% only, respectively, and no grade 4 PPE was observed. Grades 1 to 3 stomatitis was found in 58% of patients (10% grade 3). CONCLUSION: The combination of L-DXR and GEM is an active and acceptably tolerated option in the treatment of patients with platinum-resistant and -refractory ovarian cancer. Dose reductions seem advisable in the case of > or =grade 2 stomatitis and/or PPE > or =grade 2.

Spontaneous regression of CIN and delayed-type hypersensitivity to HPV-16 oncoprotein E7.

We investigated delayed-type hypersensitivity to human papillomavirus (HPV) in women with cervical dysplasia or cancer. Women were challenged by skin tests with synthetic HPV-16 E7 oncoprotein peptides. 11 women were regressors (cleared disease without treatment) and 37 were progressors (required surgery). Antibodies to early antigens (markers for progression) were detectable in a higher proportion of cancer patients than all other patients, particularly progressors with cervical intraepithelial neoplasia (CIN). By contrast, cellular immunity to HPV-16 E7, measured by skin test, was significantly (p=0.0001) associated with clinical and cytological resolution of HPV-induced CIN, indicating that E7-specific T-helper cells have a role in control of HPV.

DNA ploidy determination of early molar pregnancies by image analysis: comparison to histologic classification.

BACKGROUND: To improve histologic diagnosis of molar pregnancies, updated guidelines have been proposed recently. These guidelines take into account that less developed molar gestations differ from their fully developed counterparts. OBJECTIVE: To test the validity of these criteria by correlating histologic diagnosis with ploidy determination accomplished by means of image analysis. DESIGN: Fifty archival cases of early molar pregnancy were reclassified according to the new criteria. The diagnosis had to be changed from partial to complete hydatidiform mole (PM to CM, respectively) in 9 cases and from CM to PM in 4 cases. DNA image cytometry could be performed in 40 cases (CM, n = 21; PM, n = 19). RESULTS: There was 100% agreement between histologic diagnosis and a diploid or polyploid histogram in CM and 79% agreement between triploidy and PM, when the updated diagnostic criteria were used. This represents an improvement compared with diagnoses made with former criteria. Nevertheless, problems of correct classification remain: In 3 cases classified as PMs, fetal remnants were accompanied by the histologic appearance of a CM. These 3 cases could represent either a true embryonic development in CM or a twin gestation with one normal pregnancy and one mole, or they could belong to a (very rare) third type of mole. All of them show the same risk of persistent trophoblastic disease observed in classic CM. CONCLUSIONS: As the groups at risk for developing persistent trophoblastic disease can be identified by their DNA histograms, ploidy analysis would be desirable in addition to histologic examination.

Fulminant course of a microinvasive vulvar carcinoma in an immunosuppressed woman.

Iatrogenic immune suppression following renal transplantation is frequently associated with certain neoplasms, including vulvar carcinoma. We describe a patient with a vulvar carcinoma less than 1 mm depth of invasion and less than 3 mm superficial spread 12 years after renal transplantation. A simple vulvectomy was performed but 4 months later disease recurred in the inguinal nodes. The patient died 20 months later with progressive disease in the retroperitoneum and liver metastases.

[Ultrasound morphologic evaluation of the postmenopausal endometrium. A prospective study]. / Sonomorphologische Beurteilung des postmenopausalen Endometriums. Eine prospektive Studie.

OBJECTIVE: The measurement of the endometrial thickness by means of transvaginal sonography has been discussed as a tool for cancer screening. The aim of the study was to evaluate such a sonomorphological characterization of the endometrium performed by physicians in training. METHODS: A transvaginal sonography was performed in 400 patients before histological examination (dilatation and curettage or hysterectomy). The endometrial thickness measured as double layer and the sonographic patterns were determined. RESULTS: The endometrial thickness correlated with the histological findings: the median thickness was 6 mm for the normal endometrium and increased to 9 mm for polypiform hyperplasias 9.5 for cervical mucous polyps, and to 14 mm for glandular-cystic hyperplasias and carcinomas (p < 0.001 vs. normal). The sonomorphological grading score was also associated with the histology. For the sonomorphological grading, the sensitivity decreased to 80%, but the specificity increased to 62%. CONCLUSIONS: The sonomorphological pattern is superior to the sole determination of the endometrial thickness. This method is practicable under routine conditions performed by physicians in training. However, the specificity of both methods is too low to recommend them for cancer screening.