Evaluation of dyskerin expression and the Cajal body protein WRAP53ß as potential prognostic markers for patients with primary vaginal carcinoma.

Primary vaginal cancer (PVC) is a rare gynaecological malignancy, which, at present, lacks appropriate biomarkers for prognosis. The proteins dyskerin and WD repeat containing antisense to TP53 (WRAP53ß), both of which exert their functions in the telomerase holoenzyme complex, have been shown to be upregulated in different cancer types. These proteins have also been proposed as prognostic markers in some types of cancer. The aim of the present study was to examine the expression patterns of dyskerin and WRAP53ß in patients with PVC. Moreover, as part of a search for effective biomarkers to evaluate prognosis in PVC, the expression of these two proteins and their potential association with clinical variables and survival were also evaluated. The expression of dyskerin and WRAP53ß was assessed in PVC tumour samples from 68 patients using immunohistochemistry. The majority of tumour samples showed low and moderate expression levels of dyskerin. Upregulation of dyskerin in tumour samples was significantly associated with a shorter survival time and a poorer cancer-specific survival rate. WRAP53ß was also expressed in most of the cells but was not significantly associated with clinical variables or survival. This study demonstrates that upregulation of dyskerin is significantly associated with poor prognosis. Thus, dyskerin may serve as a promising prognostic marker and a potential putative therapeutic target in PVC.

Combined external pelvic chemoradiotherapy and image-guided adaptive brachytherapy in treatment of advanced cervical carcinoma: experience from a single institution.

PURPOSE: External pelvic chemoradiotherapy and image-guided adaptive brachytherapy (IGABT) were studied in advanced cervical carcinomas. Treatment modalities were defined and related to outcomes and side effects. MATERIAL AND METHODS: From a single cancer center, 138 patients with advanced cervical cancer were recruited. All patients were treated with external radiotherapy and IGABT. A dosimetric study was performed and related to treatment outcome and side effects. Toxicity of the organs at risk was evaluated by the CTCAE-grading system. RESULTS: The median follow-up was 44 months. More than 60% of the tumors were FIGO stage IIB-IIIB and 82% were squamous cell carcinomas. Largest tumor size (width) was in mean 41 mm and 27% had lymph node spread. The mean total external dose was 51 Gy, and the mean total dose to the high-risk clinical target volume (HRCTV) was 88 Gy. In 130 patients (94%), weekly cisplatin was given in 4-6 cycles. The median number of brachytherapy fractions was four, and in 86 patients, interstitial needles were applied. The primary local control was 97% and 94% after four local recurrences. The overall pelvic control was 89%. The overall recurrence rate was 25% and distant metastases rate was 22%. The overall 5-year survival rate was 65% and cancer-specific survival rate was 69%. Prognostic factors were FIGO stage and total brachytherapy dose (D90) to HRCTV. Late serious toxicity of the bladder and intestine were rare, occurring in only 3% of patients. CONCLUSIONS: The local and pelvic control rates were excellent in this series. The IGABT was an important part of the treatment schedule and could probably not be replaced by increasing the external pelvic dose. Adenocarcinomas seemed to benefit from the addition of interstitial needles. Late serious toxicity was rare.

HPV-negative Tumors in a Swedish Cohort of Cervical Cancer.

Despite the common perception that the human papilloma virus (HPV) is a requirement for the development of cervical cancer (CC), a considerable number of CCs test HPV negative. Presently, many countries are shifting to HPV primary CC screening, and it is of importance to increase the knowledge about the group of CCs that test HPV negative. The aim of this study was to reinvestigate a proportion of cervical tumors with a primary negative or invalid test result. Reinvestigation with repeated genotyping (targeting L1) was followed by analysis with an alternative target method (targeting E6/E7) on existing or additional tumor material. Consistently negative tumors were histologically evaluated, and cases with low or lacking tumor cell content, consistent invalid test results, or with suspicion of other than cervical origin were excluded. HPV-negative cases were thereafter subjected to immunohistochemistry (Cytokeratin 5, pan cytokeratin, protein 63, P16, and P53). The HPV-negative proportion could after reinvestigation be reduced by one-half (14%-7%). Additional positive samples were often detected in late polymerase chain reaction cycles, with an alternative (E6/E7) or the same (L1) target, or with a method using shorter amplicon lengths. Confirmed HPV negativity was significantly associated with worse prognosis, high patient age, longer storage time, and adenocarcinoma histology. Some of the HPV-negative cases showed strong/diffuse p16 immunoreactivity, indicating some remaining false-negative cases. False HPV negativity in this cohort was mainly linked to methodological limitations in the analysis of stored CC material. The small proportion of presumably true HPV-negative adenocarcinomas is not a reason for hesitation in revision to CC screening with primary HPV testing.

Quality Indicators and Survival Outcome in Stage IIIB-IVB Epithelial Ovarian Cancer Treated at a Single Institution.

BACKGROUND/AIM: To investigate the overall survival rate, quality indicators and treatment outcome in FIGO stage IIIB-IVB epithelial ovarian cancer at a University Hospital in Sweden between 2006 and 2015. MATERIALS AND METHODS: A cohort of 110 patients was followed-up for 3-12 years after cancer diagnosis. Three main groups (primary surgery, neoadjuvant chemotherapy, palliative treatment), and six subgroups were defined according to treatment modality. RESULTS: The mean age was 65 years. Patients were observed for a mean of 50 months. The total resection frequency was 83%. Significant differences in overall survival at 5 years were observed between the groups varying from 60% to 12%. CONCLUSION: Patient age, tumor stage and complete tumor removal at surgery were significant, independent prognostic factors of overall survival. Complication rate was a significant adverse prognostic factor in univariate analysis. Data discrepancy was observed between public quality reports and locally obtained data.

HPV16 viral characteristics in primary, recurrent and metastatic vulvar carcinoma.

Vulvar carcinoma is the fourth most common gynecological malignancy. Two separate carcinogenic pathways are suggested, where one is associated with the human papillomavirus (HPV) and HPV16 the most common genotype. The aim of this study was to evaluate HPV-markers in a set of primary tumors, metastases and recurrent lesions of vulvar squamous cell carcinomas (VSCC). Ten HPV16-positive VSCC with metastatic regional lymph nodes, distant lymphoid/hematogenous metastases or local recurrent lesions were investigated for HPV genotype, HPV16 variant, HPV16 viral load, HPV16 integration and HPV16 E2BS3 and 4 methylation. In all 10 analyzed case series, the same HPV genotype (HPV16), HPV16 variant and level of viral load were detected in all lesions within a patient case. Primary tumors with a high E2/E6 ratio were found to have fewer vulvar recurrences and/or metastases after diagnosis and treatment. Also, a significantly lower viral load was evident in regional lymph nodes compared to primary tumors. The data presented strengthens the evidence for a clonal HPV-induced pathway for vulvar carcinoma.

Findings of multiple HPV genotypes in cervical carcinoma are associated with poor cancer-specific survival in a Swedish cohort of cervical cancer primarily treated with radiotherapy.

Cervical cancer (CC) is one of the most common cancers in women and virtually all cases of CC are a result of a persistent infection of human papillomavirus (HPV). For disease detected in early stages there is curing treatment but when diagnosed late with recurring disease and metastasis there are limited possibilities. Here we evaluate HPV impact on treatment resistance and metastatic disease progression. Prevalence and distribution of HPV genotypes and HPV16 variants in a Swedish CC patient cohort (n=209) was evaluated, as well as HPV influence on patient prognosis. Tumor samples suitable for analysis (n=204) were genotyped using two different real-time PCR methods. HPV16 variant analysis was made using pyrosequencing. Results showed that HPV prevalence in the total series was 93%. Of the HPV-positive samples, 13% contained multiple infections, typically with two high-risk HPV together. Primary cure rate for the complete series was 95%. Recurrence rate of the complete series was 28% and distant recurrences were most frequent (20%). Patients with tumors containing multiple HPV-strains and particularly HPV genotypes belonging to the alpha 7 and 9 species together had a significantly higher rate of distant tumor recurrences and worse cancer-specific survival rate.

Expression of LRIG proteins as possible prognostic factors in primary vaginal carcinoma.

BACKGROUND: Primary vaginal carcinoma (PVC) is a rare malignancy. Established prognostic factors include tumour stage and age at diagnosis. The leucine-rich repeats and immunoglobuline-like domains (LRIG)-1 protein functions as a tumour suppressor, but less is known about the functions of LRIG2 and LRIG3. The present study aimed to evaluate the expression of LRIG proteins and analyse their possible associations with clinical characteristics and survival in a cohort of PVC patients. METHODS: We used immunohistochemistry to investigate LRIG1, LRIG2, and LRIG3 expression in tumour samples from a consecutive cohort of 70 PVC patients. The association between LRIG protein expression and clinical characteristics and cancer-specific survival was investigated using univariate and multivariate analyses. RESULTS: The majority of PVC patients (72%) had >50% LRIG1- and LRIG2-positive cells, and no or low LRIG3-positive cells. HPV status was significantly correlated with LRIG1 expression (p = 0.0047). Having high LRIG1 expression was significantly correlated with superior cancer-specific survival in univariate and multivariate analyses. LRIG2 and LRIG3 expression did not significantly correlate with clinical characteristics or survival. CONCLUSION: LRIG1 expression might be of interest as a prognostic marker in PVC patients, whereas the role of LRIG2 and LRIG3 expression remains to be clarified.

Does p53 codon 72 polymorphism have a prognostic value in carcinoma of the vulva and vagina?

Human papilloma virus (HPV) is considered to be responsible for a large part of vaginal and vulvar carcinomas, and the p53 codon 72 polymorphism has been implicated in susceptibility to cancer induced by this virus, but with contradicting results. In this study, we have investigated the prognostic value of the codon 72 polymorphism by real-time PCR (qPCR) in two cohorts of vaginal (n = 66) and vulvar (n = 123) carcinomas. In vaginal carcinoma, arginine homozygous patients were significantly associated with a higher primary cure rate (p = 0.023) but also associated with a higher recurrence rate (p = 0.073), significant at distant locations (p = 0.009). No significant differences were found in overall survival rate (p = 0.499) or cancer-specific survival rate (p = 0.222). A higher frequency of arginine homozygosity was noted in HPV-positive tumors (p = 0.190) in comparison with HPV-negative tumors. In vulvar carcinoma, the genotype homozygous for arginine was significantly associated with a larger tumor size at diagnosis in the entire cohort (p = 0.015) and a lower cancer-specific survival rate (p = 0.024) compared with heterozygous (arginine/proline) in HPV-negative tumors. Our results indicate that the relation between HPV and the p53 codon 72 polymorphism is complex and the significance and mechanisms responsible for this relationship need to be further elucidated.

Epigenetic changes as prognostic predictors in endometrial carcinomas.

Endometrial carcinoma is one of the most frequent gynecological malignancies of the female. The diagnostic and prognostic markers for the high-risk subgroups with unfavorable prognosis are under intense debate worldwide, and, therefore, the aim of this study was to identify new potential DNA methylation markers for the high-risk groups. We used the Illumina Infinium HumanMethylation450 BeadChip to analyze the DNA methylation pattern and investigated its association with clinicopathological features important for defining the high-risk (FIGO-grade 3) and low-risk (FIGO-grade 1) groups of patients with endometrial cancer (n = 31 and n = 39, respectively). We identified specific DNA methylation signature in high-risk endometrial tumors, and potential molecular biomarker genes (TBX2, CHST11, and NID2) associated with unfavorable clinical predictive and prognostic factors.

Differences in outcome for cervical cancer patients treated with or without brachytherapy.

PURPOSE: To compare the clinical outcome of cervical cancer patients treated with primary radiotherapy with and without the addition of brachytherapy. METHODS AND MATERIALS: In all, 220 patients with cervical cancer stage I-IV treated between 1993 and 2009 were included. Three or five 6.0 Gy fractions of brachytherapy were given in addition to the external beam radiotherapy to 134 patients, whereas 86 patients received external beam radiotherapy alone (EBRTA). In the EBRTA group, the patients received external boost instead of brachytherapy with a total dose to the tumor of 64-72 Gy. RESULTS: The 5-year overall survival and cancer-specific survival rates of the complete series were 42.5% and 55.5%, respectively. The rates of primary complete remission, 5-year cancer-specific survival, and recurrence were 92.5%, 68.5%, and 31.3% for the brachytherapy group vs. 73.3%, 35.4%, and 37.2% for the EBRTA group. The survival (all types) of the patients receiving brachytherapy was significantly (p < 0.0001) better than for the patients treated with external boost, but the difference was most pronounced in FIGO stage II tumors. Higher FIGO stage, nonsquamous cell carcinoma histology, treatment with EBRTA, and lower total equal 2-Gy (EQD2) external dose were significantly associated with poorer survival, lower rate of remission, and higher recurrence rate in multivariate models. CONCLUSIONS: Primary tumor remission rate, recurrence rate, and all types of survival rates were improved in the brachytherapy group. Brachytherapy is important to achieve sufficient doses to the periphery and central part of the tumor and should always be considered in treatment of cervical carcinomas.

Prognostic impact of the expression of Wnt-signaling proteins in cervical carcinoma FIGO stage I-IV treated with radiotherapy or chemoradiotherapy.

Wnt signaling proteins were assessed in patients with primary cervical carcinomas who received chemoradiation. The associations between three Wnt signaling proteins and prognosis were assessed. Specimens from 122 patients with cervical carcinomas (FIGO stage I-IV) were immunohistochemically (IHC) analyzed for ß-catenin, APC and axin protein expression. Associations between these Wnt-protein expressions, clinicopathological factors, and clinical outcome data were examined.Positive IHC staining for the ß-catenin protein (cell-membranes, cytoplasm and nuclei) was recorded in 88%, 58% and 5%, respectively. There was a strong association between ß-catenin staining of the cell-membranes and prediction of recurrences and prognosis (p = 0. 002). Tumors with > 5% of nuclear ß-catenin staining were associated with inferior cancer-specific survival (p = 0.048) compared with no staining. The overall recurrence rate was significantly higher in the group with increased nuclear staining (67%) compared with the group with no staining (33%). Nuclear APC staining of high intensity was associated with a significantly worse cancer-specific survival and increased overall recurrence rate compared to tumors with weak staining. Distant recurrences were recorded in 29% of cases with intense staining and in 14% of cases with low staining.The Wnt signaling pathway seems to be of importance in the process of cervical oncogenesis. A predictive and prognostic value was found for ß-catenin, where strong cell-membrane staining was favorable, and > 5% positive nuclear staining was associated with poorer cancer-specific survival and overall recurrence rate. Nuclear APC staining intensity was also associated with a less favorable prognosis.

Prognostic importance of DNA ploidy in non-endometrioid, high-risk endometrial carcinomas.

The present study investigated the predictive and prognostic impact of DNA ploidy together with other well-known prognostic factors in a series of non-endometrioid, high-risk endometrial carcinomas. From a complete consecutive series of 4,543 endometrial carcinomas of International Federation of Gynecology and Obstetrics (FIGO) stages I-IV, 94 serous carcinomas, 48 clear cell carcinomas and 231 carcinosarcomas were selected as a non-endometrioid, high-risk group for further studies regarding prognosis. The impact of DNA ploidy, as assessed by flow cytometry, was of particular focus. The age of the patients, FIGO stage, depth of myometrial infiltration and tumor expression of p53 were also included in the analyses (univariate and multivariate). In the complete series of cases, the recurrence rate was 37%, and the 5-year overall survival rate was 39% with no difference between the three histological subtypes. The primary cure rate (78%) was also similar for all tumor types studied. DNA ploidy was a significant predictive factor (on univariate analysis) for primary tumor cure rate, and a prognostic factor for survival rate (on univariate and multivariate analyses). The predictive and prognostic impact of DNA ploidy was higher in carcinosarcomas than in serous and clear cell carcinomas. In the majority of multivariate analyses, FIGO stage and depth of myometrial infiltration were the most important predictive (tumor recurrence) and prognostic (survival rate) factors. DNA ploidy status is a less important predictive and prognostic factor in non-endometrioid, high-risk endometrial carcinomas than in the common endometrioid carcinomas, in which FIGO and nuclear grade also are highly significant and important factors.

Viral load, integration and methylation of E2BS3 and 4 in human papilloma virus (HPV) 16-positive vaginal and vulvar carcinomas.

OBJECTIVE: To investigate if viral load, integration and methylation of E2BS3 and 4 represent different ways of tumor transformation in vaginal and vulvar carcinoma and to elucidate its clinical impact. METHODS: Fifty-seven samples, positive for HPV16, were selected for the study. Detection of viral load was made with realtime-PCR using copy numbers of E6 and integration was calculated from comparing E2 to E6-copies. Methylation of E2BS3 and 4 was analysed using bisulphite treatment of tumor DNA, followed by PCR and pyrosequencing. RESULTS: Vaginal tumors were found to have a higher viral load (p = 0.024) compared to vulvar tumors but a high copy number (> median value, 15,000) as well as high methylation (>50%) was significantly (p = 0.010 and p = 0.045) associated with a worse cancer-specific survival rate in vulvar carcinoma, but not in vaginal carcinoma. Four groups could be defined for the complete series using a Cluster Two step analysis; (1) tumors holding episomal viral DNA, viral load below 150,000 copies not highly methylated (n = 25, 46.3%); (2) tumors harboring episomal viral DNA and being highly methylated (>50%; n = 6, 11.1%); (3) tumors with viral DNA fully integrated (n = 11, 20.4%), and (4) tumors harboring episomal viral DNA and being medium- or unmethylated (<50%) and having a high viral load (> total mean value 150,000; n = 12, 22.2%). The completely integrated tumors were found to be distinct group, whilst some overlap between the groups with high methylation and high viral load was observed. CONCLUSION: HPV16- related integration, methylation in E2BS3 and 4 and viral load may represent different viral characteristics driving vaginal and vulvar carcinogenesis. HPV16- related parameters were found to be of clinical importance in the vulvar series only.

Natural history of recurrences in endometrial carcinoma.

The aim of the present study was to evaluate the natural history of endometrial cancer recurrences with regard to predictive and prognostic factors. Between 1990 and 1999, 100 patients were treated for recurrences of endometrial carcinoma (all FIGO stages). Overall, 90 tumors were of endometrioid type. A total of 82 patients were treated with surgery, 41 patients received adjuvant external irradiation and 91 patients received vaginal brachytherapy. The median time to recurrence (TTR) was 32 months. The recurrences were treated using a combination of high-dose-rate brachytherapy and external pelvic irradiation in 35 cases. In addition, 44 patients were treated with chemotherapy and 21 patients received other types of therapy. The complete remission rate was 29% and the overall response rate was 44%. Among patients treated with radiotherapy, the response rate was 88% and, for those treated with chemotherapy, the rate was 33%. The local control of vaginal recurrences treated with combined radiotherapy was 93%. In 45 patients (45%) a second recurrence was identified and a third recurrence occurred in 12 patients. The overall five-year survival rate was 44%. Age, FIGO grade, nuclear grade, TTR and response to treatment were found to be independent and significant prognostic factors for overall survival rate. Locoregional recurrences were associated with a generalized extra-pelvic disease in 63% of the cases.

Combined external and intracavitary irradiation in treatment of advanced cervical carcinomas: predictive factors for treatment outcome and early and late radiation reactions.

OBJECTIVE: The objective of this study was to find out predictive factors of tumor control as well as acute and late radiation reactions in treatment of advanced cervical carcinomas. METHODS: In a series of 134 primary cervical carcinomas in International Federation of Gynecology and Obstetrics stages I to IV treated with combined external pelvic and intraluminal cervical-vaginal brachytherapy, predictive and prognostic factors were analyzed with regard to tumor control, recurrences, survival data, and adverse effects. Concomitant chemotherapy was given to 48 patients (35.8%). The external beam therapy was given with a 4-field technique (50-60 Gy) and brachytherapy was given with a high-dose rate (iridium-192) afterloading technique using a ring applicator set. A computed tomographically based 3-dimensional dose-planning system was used for the external beam therapy and for the brachytherapy planning. The mean age of the patients was 65 years. A total of 110 tumors were squamous cell carcinomas and 24 were adenocarcinomas or adenosquamous carcinomas. A total of 111 tumors were in International Federation of Gynecology and Obstetrics stages I to II; 23 tumors, in stages III to IV. RESULTS: The primary control rate of the complete series was 92.5%. Tumor size, the brachytherapy dose, the combined external and brachytherapy dose, as well as the number of days of interruption (delay) of irradiation were all significant predictive factors for local tumor control. Forty recurrences (30%) were recorded. Early radiation reactions were recorded in 67% (mostly grade 1) and were associated with the widths of the anterior-posterior and lateral pelvic fields. Serious late radiations reactions (grade 3-4) were noted in 11%. CONCLUSIONS: The width of the lateral pelvic fields, left point A and B doses, dose to the rectal reference point, as well as asymmetry of the dose distribution were associated with late severe reactions. Prior abdominal and pelvic surgery was also a high-risk factor for late tissue reactions. Concomitant chemotherapy did not increase the risk for acute or late toxicity.

Prognostic impact of the expression of Hedgehog proteins in cervical carcinoma FIGO stages I-IV treated with radiotherapy or chemoradiotherapy.

OBJECTIVE: Hedgehog signaling proteins were assessed in patients with cervical carcinoma receiving chemoradiation. Associations between five Hedgehog proteins and prognosis were studied. METHODS: In all, 131 cases of cervical carcinomas (FIGO stages I-IV) were immunohistochemically (IHC) analyzed for Patched (PTCH), Smoothened (SMO), and GLI1, GLI2 and GLI3 protein expression. Associations between Hedgehog protein expressions, clinicopathological factors, and clinical outcome data were examined. RESULTS: Positive IHC staining for the five Hedgehog proteins was recorded in 8% to 37% of the tumor cells. The highest frequency was noted for SMO and the lowest for GLI1. There was a significant association between low SMO- and GLI2-expression and KRAS-mutation. Tumors with overexpressed SMO had a higher frequency of residual tumor or local recurrences than tumors with low SMO expression. Patients with tumors expressing PTCH in more than 75% of the cells had significantly (P=0.023) better recurrence-free survival than patients with tumors with low expression. The opposite situation was true for SMO. For GLI2, there was a statistically significant difference with regard to overall (P=0.004) and distant (P=0.015) relapse rate for groups with expression of GLI2 in the range of 5-25% compared to higher rates. CONCLUSIONS: A predictive and prognostic value was found for PTCH, SMO, and GLI2 with regard to residual carcinoma, local recurrences, and for GLI2 distant relapses. The Hedgehog signaling pathway also seems to play an important role in cervical carcinogenesis together with HPV16-infection and KRAS-mutation.

Whole genome expression profiling of blood cells in ovarian cancer patients -prognostic impact of the CYP1B1, MTSS1, NCALD, and NOP14.

Ovarian cancer patients with different tumor stages and cell differentiation might be distinguished from each other by gene expression profiles in whole blood cell mRNA by the Affymetrix Human Gene 1.0 ST Array. We also examined if there is any association with other clinical variables, response to therapy, and residual tumor burden after surgery. Patients were divided into two groups, one with poor prognosis, advanced stage and poorly differentiated tumors (n = 22), and one group with good prognosis, early stage and well- to medium differentiated tumors (n = 11). Six genes were found to be differentially expressed: the PDIA3, LYAR, NOP14, NCALD and MTSS1 genes were down-regulated and the CYP1B1 gene expression was up-regulated in the poor prognosis group, all with p value <0.05, adjusted for mass comparison. In survival analyses, CYP1B1, MTSS1, NCALD and NOP14 remained significantly different (p<0.05). Patient groups did not differ in any transcript related to acute phase or immune responses. This minimal gene expression signature of prognostic ovarian cancer-related genes opens up an avenue for more practicable monitoring of ovarian cancer patients by simple peripheral blood tests, which may evolve into a tool to guide selection of curative and postoperative supportive therapies.

Lived experiences of women with recurring ovarian cancer.

BACKGROUND: Women with recurring ovarian cancer are living longer, due to advances in treatment options. They are now often outpatients, experiencing rapid encounters on treatment days. Whether this shift in care meets women's needs has been scarcely explored scientifically. PURPOSE OF THE STUDY: This study aimed to illuminate the phenomenon of living with recurring ovarian cancer as experienced by women in that condition. METHODS AND SAMPLE: A descriptive phenomenological method was used. Eight open-ended interviews with four women were performed approximately three and five years after the first recurrence of ovarian cancer. During these years the women had repeated clinically and radiologically verified recurrence requiring chemotherapy. KEY RESULTS: The phenomenon of living with recurring ovarian cancer meant that the women felt forced to pay attention to the failing body in order to avoid a potential breakdown. The growing limitation of their intermittent strength meant that strength had to be captured and protected. Sharing their lives with others was difficult, due to the different living conditions. The women found no space to mediate their experiences, either in close relationships or with health care professionals. But, the circumstances they lived under also generated a gratitude for the unexpected extra time. CONCLUSIONS: The findings revealed that the four women were grateful to live a while longer, but needed to share their state of being. The findings are indeed directed to health care professionals, who need to provide a more patient-centred care to meet the women's needs.

A study of docetaxel weekly or every three weeks in combination with carboplatin as first line chemotherapy in epithelial ovarian cancer: Hematological and non-hematological toxicity profiles.

The purpose of this study was to compare the toxicity profiles of docetaxel administered on a weekly schedule and the standard three-week schedule in the treatment of advanced primary ovarian carcinoma. Eligible patients were treated with intravenous docetaxel (30 mg/m2) on days 1, 8 and 15, and carboplatin (AUC 5) on day 1 or with docetaxel (75 mg/m2) and carboplatin (AUC 5) on day 1; Q21 days for 6 cycles. This study was a pooled study of two primary phase II studies. A total of 108 patients received the weekly schedule and 59 patients received the three-week schedule. All patients were evaluated for toxicity. The overall response rate was 79% and the biochemical response 93% for the weekly schedule. The median overall survival rate was 35.3 months. Neutropenia was significantly more common (ANOVA; p<0.0001) in the three-week group than in the weekly group during all six courses of chemotherapy. Fever and infections were also more common in this group. Thrombocytopenia and anemia were slightly more common in the weekly group. Fatigue, epiphora, nail changes and taste disturbances were specific side-effects following weekly docetaxel. Peripheral sensory neuropathy (grade 1-2) increased with every cycle of treatment, but in a similar manner in the two groups. Grade 3-4 neuropathy was not recorded. Oral mucositis and myalgia were two side-effects associated with the three-week schedule. Nausea and vomiting, diarrhea and dyspnea were a limited problem in both groups. Cardiac toxicity was rare and did not differ between the two docetaxel schedules. The weekly administration was favored due to the lower rates of neutropenia, fever, infections, oral mucositis and myalgia. However, epiphora and nail changes were specific side-effects of the weekly treatment. Both regimens appeared to be rather well tolerated with similar compliance (66 and 70%) with regard to completion of the planned six courses of chemotherapy.

A population-based series of ovarian carcinosarcomas with long-term follow-up.

AIM: The aim of the present study was to evaluate a consecutive series of ovarian carcinosarcomas with regard to prognosis, treatment and prognostic factors. PATIENTS AND METHODS: A consecutive series of 81 ovarian carcinosarcomas from two well-defined geographic regions were studied with regard to survival, type of primary and adjuvant therapy and prognostic factors. All patients but one underwent primary surgery and some patients also received adjuvant chemotherapy (platinum-based) alone or in combination with radiotherapy. Univariate and multivariate Cox proportional regression analysis was used. Survival was analyzed by the Kaplan-Meier technique and differences were assessed by the log-rank test. RESULTS: The mean age of the patients was 73 years. Fifty-one patients received adjuvant chemotherapy and nine patients pelvic irradiation. The 5-year overall survival rate was 10%. Adjuvant therapy (any type) and six completed cycles of chemotherapy were highly significant factors with regard to improved overall survival rate. The only significant tumor-associated prognostic factor was the International Federation of Gynecology and Obstetrics (FIGO) grade of the tumor. FIGO stage, site of metastatic spread, tumor size, histology, DNA ploidy, and tumor necrosis were non-significant factors. Therapy was rather well-tolerated and 29 patients (57%) completed at least six cycles of adjuvant chemotherapy. CONCLUSION: Adjuvant and completed chemotherapy according to the treatment plan were the most important prognostic factors. FIGO grade (grade 3 vs. 1-2) of the epithelial component of the tumor was also a significant prognostic factor in multivariate Cox analysis.