Disease Progression In Women Research Articles

Parity Associated with Long-Term Disease Progression in Women with Multiple Sclerosis

Parity Associated with Long-Term Disease Progression in Women with Multiple Sclerosis

OS085. Decreased maternal circulating PLGF is a significant predictor of length of pregnancy in women with hypertensive disorders of pregnancy

Diagnosis of the presence of disease and prediction of the rate of progression of disease in women with hypertensive disorders of pregnancy remains a clinical problem. Better methods are needed to determine the magnitude of risk to support patient counseling and clinical management. To investigate whether the level of free PlGF is a significant predictor of length of pregnancy in women with hypertension. In this case-control study a single sample was taken between the 22nd and 34th completed gestational weeks from 130 pregnant women with a final diagnosis of: pre-eclampsia (PE), HELLP-syndrome, superimposed pre-eclampsia (SIPE), chronic hypertension (CHT), gestational hypertension (GHT), and normal healthy pregnancy (Control). Plasma was analysed for PlGF using the Triage® PlGF assay (Alere, San Diego). A positive PlGF test was defined as below the 5th centile of normal healthy pregnancy. Hazard ratios for length-of-pregnancy were calculated for a positive PlGF test in a multivariate Cox proportional hazards model adjusting for two covariates, the gestational age at sample collection and a final diagnosis of proteinuric hypertension (PE, HELLP, and SIPE). Median PlGF concentration was significantly lower in women with hypertension than in controls. Women with proteinuric hypertension had the lowest levels of PlGF. A positive PlGF test predicted delivery before 35 weeks in 93.7% women, and delivery before 37 weeks in 90.5% women. A positive PlGF test was associated with a significantly higher risk of imminent delivery. PlGF was a significant and independent predictor of women destined to deliver early because of maternal or fetal complication (adjusted Hazard Ratio of 3.43, 95%CI of 1.97 to 5.98). A positive PlGF test is significant predictor of length of pregnancy, independent of other diagnostic criteria. PlGF has the potential to identify increased risk without the limitation of non-specificity which exists with other diagnostic parameters.

PP056. Placental growth factor is a better predictor of preterm birth than uterine or umbilical artery doppler in hypertensive disorders of pregnancy

Diagnosis of the presence of disease and prediction of the rate of progression of disease in women with hypertensive disorders of pregnancy remains a clinical problem. Adequate placentation and placental development are important for normal pregnancy. We determined whether PlGF is a better predictor of delivery before 34+0 and 37+0 weeks than uterine artery and umbilical artery doppler. One hundred and four women presenting before the completed 34th week of pregnancy with hypertensive disorders of pregnancy were enrolled into the study. Final diagnosis was chronic hypertension (N=24), gestational hypertension (N=21), pre-eclampsia (N=24), HELLP-syndrome (N=15), superimposed preeclampsia (N=20). Blood draw occurred before the 34th week of pregnancy at the time of investigation for expedited delivery or expectant management. Plasma was analysed for PlGF by the Alere Triage® PlGF assay using fluorescently-labelled monoclonal antibodies against PlGF. A positive PlGF test was defined as below the 5th centile of normal healthy pregnancy. Of the 104 pregnant women, the level of PlGF was abnormal in 23 of 24 (96%) women with IUGR, compared to 10 of 24 (42%) and 14 of 24 (58%) for uterine artery doppler and umbilical artery doppler, respectively. In the case of pre-eclampsia, the level of PlGF was abnormal in 50 of 59 (85%), compared to 15 of 59 (25%) and 25 of 56 (45%) for uterine artery doppler and umbilical artery doppler, respectively. Forty four (42%) women required medical delivery before 34+0 weeks gestation and 68 (65%) before 37+0 weeks gestation (see Table). PlGF detected a higher number of women requiring early delivery than doppler. The new Triage® PlGF test provides useful information to inform clinical decisions in pregnancy-associated hypertensive disorders, before the 34th completed gestational week.

Angiogenesis inhibitors for the treatment of ovarian cancer.

Many women with ovarian cancer eventually develop resistance to conventional chemotherapy drugs, and so novel agents are being developed to target specific molecular pathways. One such class of drugs inhibits angiogenesis (the development of new blood vessels), which is essential for tumour growth. It is important to establish whether the addition of these new drugs to conventional chemotherapy regimens improves survival, and what the side-effects may be. To compare the effectiveness and toxicities of angiogenesis inhibitors in the treatment of ovarian cancer. We sought to identify completed randomised controlled trials (RCTs) by searching The Cochrane Gynaecological Cancer Review Group's Trial Register, The Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2010, Issue 10), MEDLINE and EMBASE (1990 to October 2010). We also searched registers of clinical trials, and contacted investigators of completed and ongoing trials for further information. Randomised controlled studies comparing angiogenesis inhibitors with either standard chemotherapy or no treatment, in women with ovarian cancer. Two independent authors carried out data collection and extraction. We used a random-effects model for pooling data. We did not find any fully-published, completed RCTs of angiogenesis inhibitors that met our inclusion criteria. We identified five abstracts of completed RCTs of four different angiogenesis-inhibiting agents, with a total of 3701 participants.Meta-analysis of two trials found no statistically significant difference in overall survival (OS) between women with newly-diagnosed advanced ovarian cancer who received concurrent and maintenance bevacizumab compared to those who received chemotherapy (carboplatin and paclitaxel) alone. However, women who received concurrent and maintenance bevacizumab had their risk of disease progression reduced by a quarter (hazard ratio (HR) 0.75, 95% confidence interval (CI) 0.68 to 0.83; P < 0.001); they also had a significantly increased risk of severe gastrointestinal adverse events, moderate or severe hypertension and severe bleeding.One trial also compared chemotherapy to concurrent (but not maintenance bevacizumab), and found no statistically significant difference in OS or progression-free survival (PFS). However, the women who received bevacizumab had a significantly higher risk of moderate or severe hypertension.A three-armed RCT, of paclitaxel alone or with low- or high-dose AMG 386, in women with recurrent ovarian cancer, found no statistically significant difference in OS. However, women who received low-dose AMG 386 had a third less risk of disease progression than those who received placebo (HR 0.57, 95% CI 0.36 to 0.91; P = 0.02). The trial found no evidence of increased adverse events in the intervention arms.Two relatively small RCTs (one of VEGF-Trap, the other of BIBF 1120) found no evidence of either significant survival benefit or increased severe adverse events, compared to placebo, but they both lacked statistical power.All five trials had unclear risk of bias, largely because they have only been published in abstract form, and thus many methodological details are unclear. We identified twelve suitable ongoing trials. There is, as yet, no fully-published RCT evidence for the efficacy or safety of angiogenesis inhibitors for the treatment of ovarian cancer, but some preliminary results are available from five trials. There is some evidence from a meta-analysis of two trials that the addition of concurrent and maintenance bevacizumab to standard chemotherapy may reduce the risk of disease progression, in women with newly-diagnosed advanced ovarian cancer. There is also some evidence from a single trial that low-dose AMG 386 may reduce the risk of disease progression in women with recurrent ovarian cancer. However, there is currently no evidence that angiogenesis inhibitors improve OS, nor is there enough evidence to justify the routine use of angiogenesis inhibitors in treating women with ovarian cancer. We eagerly await both the more detailed results of these five completed trials, and the preliminary results of the several ongoing trials.

Pegylated liposomal doxorubicin: appraisal of its current role in the management of epithelial ovarian cancer.

Pegylated liposomal doxorubicin (PLD) has become a major component in the routine management of epithelial ovarian cancer. The drug is frequently employed as a single agent in the platinum-resistant setting, and recently reported data reveal the superiority of the combination of PLD plus carboplatin, compared with the platinum drug plus paclitaxel, in delaying the time to disease progression in women with recurrent (potentially platinum-sensitive) disease. Current research efforts involving PLD in ovarian cancer are focusing on adding novel targeted drugs to this cytotoxic agent. The utility of such approaches in the platinum-resistant population, compared with the sequential administration of single agents active in this setting, remains to be determined.

Pegylated liposomal doxorubicin: appraisal of its current role in the management of epithelial ovarian cancer

Pegylated liposomal doxorubicin: appraisal of its current role in the management of epithelial ovarian cancer Maurie MarkmanCancer Treatment Centers of America, Eastern Regional Medical Center, Philadelphia, PA, USAAbstract: Pegylated liposomal doxorubicin (PLD) has become a major component in the routine management of epithelial ovarian cancer. The drug is frequently employed as a single agent in the platinum-resistant setting, and recently reported data reveal the superiority of the combination of PLD plus carboplatin, compared with the platinum drug plus paclitaxel, in delaying the time to disease progression in women with recurrent (potentially platinum-sensitive) disease. Current research efforts involving PLD in ovarian cancer are focusing on adding novel targeted drugs to this cytotoxic agent. The utility of such approaches in the platinum-resistant population, compared with the sequential administration of single agents active in this setting, remains to be determined.Keywords: PLD, carboplatin, paclitaxel, platinum-sensitive, platinum-resistant

The Cost-Effectiveness of Herpes Simplex Virus-2 Suppressive Therapy With Daily Aciclovir for Delaying HIV Disease Progression Among HIV-1-Infected Women in South Africa

The Partners in Prevention HSV/HIV transmission trial (Partners HSV/HIV Transmission Study) showed that herpes simplex virus-2 (HSV-2) suppressive therapy with daily aciclovir could decrease HIV disease progression amongst HIV-1/HSV-2 coinfected individuals. The cost-effectiveness of daily aciclovir for delaying HIV-1 disease progression in women not eligible for antiretroviral therapy (ART) is estimated. Resource use/cost data for delivering daily aciclovir at a primary health care HIV clinic were collected in Johannesburg. Effectiveness estimates were obtained from the Partners HSV/HIV Transmission Study trial and epidemiologic data from South Africa. A Markov model simulated the cost-effectiveness of daily aciclovir on HIV-1 disease progression in ART-naive women. Therapy was given to all HIV-1-infected women. Cost-effectiveness was compared against cost per life-year gained (∼US $1200 per LYG) of ART provision in South Africa. For an ART eligibility criteria of CD4 count <200 cells/μL and the cheapest internationally available aciclovir (US $0.026 per day for 2 × 400 mg aciclovir), the median cost per LYG is US $1023 (95% confidence interval [CI]: 537-2842), whereas it decreases to US $737 (95% CI: 373-2489) if the ART eligibility criteria is CD4 count <350 cells/μL. Both these projections compare favorably with the estimated cost-effectiveness of ART in South Africa (∼US $1200 per LYG). The cost per LYG increases dramatically for the current aciclovir cost in South Africa (US $0.14 per day), if salary costs are higher and if HSV-2 prevalence amongst HIV-1-infected women are lower. Projections suggest HSV-2 suppressive therapy could dramatically increase the proportion of women initiating ART. HSV-2 suppressive therapy could be an affordable strategy for reducing HIV-1 disease progression and retaining women in care before ART initiation, but cheaply available aciclovir is needed.

Vascular endothelial growth factor-D over-expressing tumor cells induce differential effects on uterine vasculature in a mouse model of endometrial cancer

BackgroundIt has been hypothesised that increased VEGF-D expression may be an independent prognostic factor for endometrial cancer progression and lymph node metastasis; however, the mechanism by which VEGF-D may promote disease progression in women with endometrial cancer has not been investigated. Our aim was to describe the distribution of lymphatic vessels in mouse uterus and to examine the effect of VEGF-D over-expression on these vessels in a model of endometrial cancer. We hypothesised that VEGF-D over-expression would stimulate growth of new lymphatic vessels into the endometrium, thereby contributing to cancer progression.MethodsWe initially described the distribution of lymphatic vessels (Lyve-1, podoplanin, VEGFR-3) and VEGF-D expression in the mouse uterus during the estrous cycle, early pregnancy and in response to estradiol-17beta and progesterone using immunohistochemistry. We also examined the effects of VEGF-D over-expression on uterine vasculature by inoculating uterine horns in NOD SCID mice with control or VEGF-D-expressing 293EBNA tumor cells.ResultsLymphatic vessels positive for the lymphatic endothelial cell markers Lyve-1, podoplanin and VEGFR-3 profiles were largely restricted to the connective tissue between the myometrial circular and longitudinal muscle layers; very few lymphatic vessel profiles were observed in the endometrium. VEGF-D immunostaining was present in all uterine compartments (epithelium, stroma, myometrium), although expression was generally low. VEGF-D immunoexpression was slightly but significantly higher in estrus relative to diestrus; and in estradiol-17beta treated mice relative to vehicle or progesterone treated mice. The presence of VEGF-D over-expressing tumor cells did not induce endometrial lymphangiogenesis, although changes were observed in existing vessel profiles. For myometrial lymphatic and endometrial blood vessels, the percentage of profiles containing proliferating endothelial cells, and the cross sectional area of vessel profiles were significantly increased in response to VEGF-D in comparison to control tumor cells. In contrast, no significant changes were noted in myometrial blood vessels. In addition, examples of invading cells or tumor emboli were observed in mice receiving VEGF-D expressing 293EBNA cells.ConclusionsThese results illustrate that VEGF-D over-expression has differential effects on the uterine vasculature. These effects may facilitate VEGF-D's ability to promote endometrial cancer metastasis and disease progression.

8049 Cisplatin-based combination chemotherapy (CTX) consisting of docetaxel and cisplatin (DP) is still effective for patients with relapsed ovarian carcinoma (ROC) resistant or refractory to carboplatin-based CTX (TC: taxol/carboplatin)

Carboplatin dosing for gynecologic malignancies is traditionally based on the Jelliffe formula that lacks dose adjustment for weight. Obese women may therefore receive a sub-therapeutic carboplatin dose. This study assessed the association between BMI and outcome for ovarian cancer patients treated with carboplatin-based chemotherapy.An analysis of patients treated with carboplatin and paclitaxel on Gynecologic Oncology Group (GOG) protocol 158 was performed. The dose of carboplatin for each patient was based on an area under the curve of 7.5 and a glomerular filtration rate (GFR) derived from the Jelliffe formula which is derived from age and serum creatinine. Patients were stratified based on body mass index (BMI).A total of 387 patients were included in the analysis. The patients were stratified into three groups: normal weight (BMI < 25.0, 50%), overweight (BMI 25–29.9, 32%) and obese (BMI ≥ 30.0, 18%). Compared to pretreatment values, the obese patients had a lower relative decrease in their platelet counts (− 25% for BMI ≥ 30 vs. − 61% for BMI < 25) (p = 0.01). Similar trends were noted for relative changes in hemoglobin (p = 0.006) and hematocrit (p = 0.002). Dose reductions were required in 34% of normal weight compared to 21% of the obese women (p = 0.004). There was a trend toward increased risk for disease progression in women with a BMI ≥ 30 (RR: 1.25, 95% CI: 0.93–1.69, p = 0.14).Obese ovarian cancer patients treated with carboplatin experience substantially less toxicity than normal weight women. The lower toxicity suggests that obese patients may be receiving a substandard drug dose.

Sex differences in the Toll-like receptor-mediated response of plasmacytoid dendritic cells to HIV-1.

Manifestations of viral infections can differ between women and men, and marked sex differences have been described in the course of HIV-1 disease. HIV-1-infected women tend to have lower viral loads early in HIV-1 infection but progress faster to AIDS for a given viral load than men. Here we show substantial sex differences in the response of plasmacytoid dendritic cells (pDCs) to HIV-1. pDCs derived from women produce markedly more interferon-alpha (IFN-alpha) in response to HIV-1-encoded Toll-like receptor 7 (TLR7) ligands than pDCs derived from men, resulting in stronger secondary activation of CD8(+) T cells. In line with these in vitro studies, treatment-naive women chronically infected with HIV-1 had considerably higher levels of CD8(+) T cell activation than men after adjusting for viral load. These data show that sex differences in TLR-mediated activation of pDCs may account for higher immune activation in women compared to men at a given HIV-1 viral load and provide a mechanism by which the same level of viral replication might result in faster HIV-1 disease progression in women compared to men. Modulation of the TLR7 pathway in pDCs may therefore represent a new approach to reduce HIV-1-associated pathology.

Circulating tumor cells and FDG-PET/CT: biological and functional methods for therapeutic monitoring in metastatic breast cancer.

Abstract Abstract #6052 Introduction: The combination of Computed Tomography (CT) and [18F] Fluorodeoxyglucose - Positron Emission Tomography (FDG-PET) scanning technologies provides a more complete picture of disease activity than CT alone. Circulating tumor cell (CTC) levels were shown to be more predictive than standard imaging (CT) when used to monitor disease progression in women with metastatic breast cancer (MBC). We performed a retrospective study to compare the ability of combined FDG-PET/CT to CTC to predict clinical outcomes in patients treated for MBC.&amp;#x2028; Methods: One hundred and two MBC patients with either measurable or evaluable disease starting a new line of therapy had CTC counts and FDG-PET/CT scans done at baseline (BL) and at mid-therapy. CTC: 7.5mL of blood collected in CellSave tubes at both time points was assayed for CTC using the FDA approved CellSearch® System. Patients were categorized as having a favorable (&amp;lt;5CTC) or unfavorable (≥5CTC) outcome. Imaging: non-contrast-enhanced CT images were acquired first, then FDG-PET/CT scans were performed after administering a mean dose of 555 MBq FDG (range 444-740 MBq) to fasting patients. CT, PET, and co-registered CT-PET images were reviewed independently by 2 radiologists. The highest recorded FDG uptake was semi-quantitatively analyzed and maximum standardized uptake value (SUV) calculated with response = SUV of &amp;lt;50% in target lesions and no response = SUV of &amp;gt;50%. Changes in CTC and SUV at mid-therapy were compared to progression free survival (PFS) and overall survival (OS).&amp;#x2028; Results: CTC: 50% (51/102) patients had ≥5 CTC at baseline (BL). At mid-therapy (median 2.5 months from BL), 21/102 progressed (≥5CTC) with a median PFS of 2.8 months vs. 7.8 months for those with no progression (&amp;lt;5CTC) (p&amp;lt;0.0001). OS was 10.0 months for patients with ≥5CTC at mid-therapy vs. 29.6 months for those with &amp;lt;5CTC (p&amp;lt;0.0001). PET/CT: 48% (49/102) patients showed no response at mid-therapy with median OS = 17.4 months vs. 29.6 months for those responding (p=0.0020). Overall, there was approximately 75% concordance in predicting outcomes between imaging and CTC assay changes [Table 1]. The majority of patients with discordant results had more advanced aggressive disease, i.e., &amp;gt;2nd line chemotherapy and triple-negative disease.&amp;#x2028; &amp;#x2028; Conclusion: ≥5 CTC and/or no response at FDG-PET/CT at mid-therapy accurately predicted significantly shorter OS. Citation Information: Cancer Res 2009;69(2 Suppl):Abstract nr 6052.

Prognostic significance of the detection of human papilloma virus L1 protein in smears of mild to moderate cervical intraepithelial lesions

Objective To investigate whether it is possible to use detection of the human papillomavirus (HPV) L1 capsid protein to predict the course of mild or moderate cervical intraepithelial neoplasia (CIN). Study design Pap smears from 279 women in whom CIN 1 and CIN 2 had been diagnosed by cytology and histology, who were known to have a high-risk HPV status and had a median follow-up of 25 months, were immunohistochemically stained for the HPV L1 protein. The staining results were correlated with the clinical course of the disease. Results HPV L1-positive patients showed regression in 49.1% of cases, stable disease in 41.5%, and progressive disease in 9.4%, whereas HPV L1-negative women had progression in 25.9% of cases (regression 33.3%, stable disease 40.7%; p = 0.001). The effect was clearest in the group under 30 years of age. HPV L1-negative patients experienced progression significantly more often than women with a positive HPV L1 test (odds ratio 3.391). Conclusions HPV L1-positivity was found to have prognostic significance in relation to disease progression in women with CIN 1 and CIN 2 and particularly in those less than 30 years of age.

Carboplatin dosing in obese women with ovarian cancer: A Gynecologic Oncology Group study

Background Carboplatin dosing for gynecologic malignancies is traditionally based on the Jelliffe formula that lacks dose adjustment for weight. Obese women may therefore receive a sub-therapeutic carboplatin dose. This study assessed the association between BMI and outcome for ovarian cancer patients treated with carboplatin-based chemotherapy. Methods An analysis of patients treated with carboplatin and paclitaxel on Gynecologic Oncology Group (GOG) protocol 158 was performed. The dose of carboplatin for each patient was based on an area under the curve of 7.5 and a glomerular filtration rate (GFR) derived from the Jelliffe formula which is derived from age and serum creatinine. Patients were stratified based on body mass index (BMI). Results A total of 387 patients were included in the analysis. The patients were stratified into three groups: normal weight (BMI < 25.0, 50%), overweight (BMI 25–29.9, 32%) and obese (BMI ≥ 30.0, 18%). Compared to pretreatment values, the obese patients had a lower relative decrease in their platelet counts (− 25% for BMI ≥ 30 vs. − 61% for BMI < 25) ( p = 0.01). Similar trends were noted for relative changes in hemoglobin ( p = 0.006) and hematocrit ( p = 0.002). Dose reductions were required in 34% of normal weight compared to 21% of the obese women ( p = 0.004). There was a trend toward increased risk for disease progression in women with a BMI ≥ 30 (RR: 1.25, 95% CI: 0.93–1.69, p = 0.14). Conclusion Obese ovarian cancer patients treated with carboplatin experience substantially less toxicity than normal weight women. The lower toxicity suggests that obese patients may be receiving a substandard drug dose.

Associations of Insulin‐Like Growth Factor (IGF)–I and IGF‐Binding Protein–3 with HIV Disease Progression in Women

The insulin-like growth factor (IGF) axis has been hypothesized to influence the rate of human immunodeficiency virus (HIV) disease progression. This premise is based largely on laboratory models showing that IGF-I stimulates thymic growth and increases lymphocyte numbers and that IGF-binding protein (IGFBP)-3 has an opposing effect, inhibiting hematopoietic stem cell development. We studied 1422 HIV-infected women enrolled in a large cohort that entailed semiannual follow-up (initiated in 1994). Baseline serum samples were tested for IGF-I and IGFBP-3 to determine their associations with incident clinical acquired immunodeficiency syndrome (AIDS) and CD4+ T cell count decline prior to April 1996 (before the era of highly active antiretroviral therapy [HAART]). Low IGF-I levels (Ptrend= .02) and high IGFBP-3 levels (Ptrend= .02) were associated with rapid CD4+ T cell count decline. Only IGFBP-3, however, was significantly associated with AIDS incidence (hazard ratio for highest vs. lowest quartile, 2.65 [95% confidence interval, 1.30-5.42]; Ptrend= .02) in multivariable models. These findings suggest that serum levels of IGFBP-3 (and possibly IGF-I) are associated with the rate of HIV disease progression in women and, more broadly, that interindividual heterogeneity in the IGF axis may influence HIV pathogenesis. If correct, the IGF axis could be a target for interventions to slow HIV disease progression and extend the time before use of HAART becomes necessary.

Tumor-derived CCL5 does not contribute to breast cancer progression

Besides functioning as a chemotactic factor, CCL5 has been associated with progression of disease in women with breast cancer, immune modulation and metastasis. Here we asked whether CCL5 produced by tumor cells contributed to growth or metastasis of breast cancer. For this purpose, we used two murine mammary carcinomas, the 4T1 tumor which is metastatic and constitutively expresses CCL5, and the 168 tumor which is not metastatic and does not constitutively express CCL5. RNA interference was used to inhibit CCL5 expression from the 4T1 tumor, and a CCL5 transgene was used to express CCL5 by the 168 tumor. Six different clones of 4T1 that exhibited stable reduction in CCL5 expression, and three different clones of 168 that exhibited stable CCL5 expression were compared to the parental tumors and vector transfected controls. Significantly, in both models, tumor-derived CCL5 expression did not correlate with MHC expression, growth rate, or metastatic ability of the tumors. These results show that tumor-derived CCL5 expression alone does not make a significant contribution to breast cancer progression.

Responsiveness to change due to supportive-expressive group therapy, improvement in mood and disease progression in women with metastatic breast cancer

Responsiveness to change due to supportive-expressive group therapy, improvement in mood and disease progression in women with metastatic breast cancer

Responsiveness to change to change due to supportive-expressive group therapy, improvement in mood and disease progression in women with metastatic breast cancer

To compare the responsiveness of six questionnaires using three hypotheses of change: (i) change due to supportive-expressive group therapy (SEGT), (ii) improved mood defined as a small effect size (.2) on Profile of Mood States (POMS) Total Mood Disturbance score and (iii) progression of disease. Data from the "Breast Expressive-Supportive Therapy" study, a multicentre randomized controlled trial of change due to SEGT versus standard of care in women with metastatic breast cancer were used. Questionnaires studied were: POMS, Impact of Event Scale, Psychosocial Adjustment to Illness Scale (PAIS), EORTC QLQ-C30, Mental Adjustment to Cancer and a Pain visual analog scale (VAS). Responsiveness to change was evaluated using the standardized response mean. POMS was used as the standard. POMS was the most responsive questionnaire to change due to SEGT. Questionnaires measuring psychosocial attributes were responsive to improvement in mood. EORTC QLQ-C30, PAIS, PAIN VAS and MAC were the most responsive to disease progression. More responsive questionnaires were associated with the smallest sample size required to detect an effect. Responsiveness to change is context specific. The POMS was the most responsive questionnaire to psychosocial therapy.

A randomized phase III comparative trial of immediate consolidation with high-dose chemotherapy and autologous peripheral blood progenitor cell support compared to observation with delayed consolidation in women with metastatic breast cancer and only bone metastases following intensive induction chemotherapy

The prognosis for patients with metastatic breast cancer remains poor. Metastatic breast cancer confined to the bones may have a better prognosis, especially hormone receptor-positive disease. We performed a prospective, randomized clinical trial to compare immediate consolidation with high-dose chemotherapy and hematopoietic support versus observation with high-dose consolidation at the time of disease progression in women with metastatic breast cancer and only bone metastases. The patients received chemotherapy with doxorubicin, 5-fluorouracil and methotrexate before randomization. In all, 85 patients were enrolled and 69 were randomized. The median follow-up is 8.1 years from randomization. The median event-free survival (EFS) for the immediate transplant arm is 12 months and for the observation arm is 4.3 months (P<0.0001). The median overall survival for the immediate transplant arm is 2.97 years and for the observation arm 1.81 years, a difference that is not statistically significant. Immediate high-dose chemotherapy and radiation therapy as consolidation offers a clinically and statistically significant improvement in EFS compared with radiation therapy alone following induction chemotherapy for women with metastatic breast cancer confined to the bones.

Neuropsychological functioning in a cohort of HIV- and hepatitis C virus-infected women

To evaluate the neurocognitive function in 220 women enrolled in the Women's Interagency HIV Study (WIHS), a study of disease progression in women living with HIV/AIDS and in HIV-negative controls. We evaluated the prevalence of abnormal neuropsychological (NP) results in hepatitis C virus (HCV)-positive compared with HCV-negative women in combination with HIV serostatus. NP impairment was significantly higher for HCV-positive women in comparison with HCV-negative women [odds ratio (OR), 2.03; 95% confidence interval (CI), 1.17-3.51]. Women co-infected with HCV and HIV demonstrated greater abnormal NP performance than those not infected with either, particularly if there was evidence of CD4 T-lymphocyte immunosuppression [> 200 x 10(6) CD4 cells/l (OR, 3.48; 95% CI, 1.49-8.15) and < or = 200 x 10(6) CD4 cells/l (OR, 5.38; 95% CI, 1.46-19.84)]. Women who were HCV-positive/HIV-positive and not taking antiretroviral therapy (ART) were more likely (OR, 7.03; 95% CI, 2.63-18.82) to demonstrate NP impairment than those who were HCV-negative/HIV-negative. In analyses controlling separately for education, intelligence quotient, depression, sedating drug use, head injury, ethnicity, and history of substance use, HCV continued to significantly predict NP impairment. The HCV effect did not reach significance when controlling for age in bivariate or multivariate analyses although the odds ratio for NP abnormalities in HCV-infected patients was only slightly reduced (ORs above 1.9). After testing for an interaction between age and infection status, we conducted age-stratified analysis and showed a significant effect of infection status for those aged under 40 years. The effect of aging on co-infected populations will require further study. This study has demonstrated the association of HCV with the risk of neurocognitive impairment in women living with HIV/AIDS and suggests that co-infection has an additive effect.

Examples of the marked variability in the relationship between the serum CA-125 antigen level and cancer-related symptoms in ovarian cancer

Objective. While the clinical utility of the serum CA-125 antigen level in demonstrating objective evidence of regression or progression of disease in women with ovarian cancer is well-established, the relationship between both the absolute value of this tumor maker, or its rate of change over time, and the short-term clinical course (e.g., development of cancer-related symptoms) in individual patients remains poorly defined. Case reports. Five women currently under the care of physicians in the Gynecologic Cancer program of the Cleveland Clinic demonstrate the marked variability in the correlation between the serum CA-125 antigen and the natural history of disease for individual patients with ovarian or primary peritoneal cancers. In these cases, persistent elevations (>100 units/ml for >2 years), rapid changes (<200 units/ml to >2000 units/ml over ≤2 months), or extremely high CA-125 values (>5000 units/ml) failed to accurately predict the presence, time to development, or severity of symptoms. Conclusion. In the second-line and palliative management of ovarian or primary peritoneal cancers, it is important to emphasize the critical need for clinical judgement in the decision to initiate or alter therapy in individual patients based solely on changes in the serum level of the CA-125 antigen.