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Gynecologic Oncology 05/2013; · 3.89 Impact Factor
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ABSTRACT: Measuring CA15.3 serum levels in the early breast cancer setting is not recommended by current ASCO guidelines. In this large single center study, we assess the prognostic value of preoperative (n = 3746), postoperative (n = 4049) and change in (n = 3252) CA15.3, also across different breast cancer phenotypes. Preoperative, postoperative and change in CA15.3 were all significant (p = 0.0348, p < 0.0001, p < 0.0001 respectively in multivariate analysis) predictors of distant metastasis free survival. For breast cancer specific survival, only postoperative and change in CA15.3 were significant predictors (p < 0.0001 both). Multivariate prognostic models did not improve by incorporating information on preoperative CA15.3, but did improve when introducing information on postoperative CA15.3 for distant metastasis (p = 0.0365) and on change in CA15.3 for breast cancer specific survival (p = 0.0291). Change in CA15.3 impacts on prognosis (distant metastasis) differently in different breast cancer phenotypes. A decrease in CA15.3 may be informative of improved prognosis in basal like and HER2 like breast cancer.
Breast (Edinburgh, Scotland) 04/2013; · 2.09 Impact Factor
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ABSTRACT: OBJECTIVE: Based on its expression profile, folate receptor alpha (FRA) is an attractive candidate for targeted diagnostics and therapeutics. However, applicability of these agents in residual or recurrent disease could be influenced by chemotherapy. We evaluated whether chemotherapy modified FRA expression in non-mucinous epithelial ovarian (EOC) and endometrial carcinoma (EC). METHODS: FRA staining was evaluated by immunohistochemistry, using MAb 26B3, in 81 patients (41 EOCs, 40 ECs) and 17 control tissues (5 benign ovarian cysts, 5 normal ovarian, 7 normal endometrial tissues). Chemotherapy effect was evaluated in 42 patients (30 paired samples at primary and interval debulking surgery, 12 from primary and recurrent disease). FRA expression was assessed using a semi-quantitative staining algorithm, the M-score (range 0-50). RESULTS: Median difference in M-score between tumor and control samples was 27.5 for EOC (95% CI 10.0 to 45.0) and 6.7 for EC (95% CI -6.7 to 21.7). Paired samples from both primary and interval debulking surgery did not differ in FRA expression in EOC (median difference of M-score between paired samples of 0.0 [95% CI -2.6 to 2.6]). Recurrent EOC tumors reflected FRA status at diagnosis (median difference of M-score between paired samples of 3.3 [95% CI -7.0 to 13.6]). CONCLUSIONS: This study shows no significant difference in FRA expression after chemotherapy, strengthening the rationale for FRA targeted diagnostics and therapeutics in FRA expressing tumors, whether newly diagnosed or at recurrence.
Gynecologic Oncology 04/2013; · 3.89 Impact Factor
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ABSTRACT: AIMS: Investigate the role of expansile versus infiltrative type of primary invasive intestinal type mucinous epithelial ovarian carcinoma (mEOC) in predicting recurrence and lymph node metastases. METHODS: Retrospective study. Differentiation was defined according to the Shimizu-Silverberg and expansile/infiltrative type according to the Lee-Scully criteria. RESULTS: Out of 104 patients with mucinous ovarian carcinomas, 44 primary invasive mucinous epithelial carcinomas of the intestinal type (mEOC) were identified. Patients with a mEOC of the expansile type are mainly diagnosed in stage I (21 out 23) and have an excellent prognosis (no relapses in 21 Stage I patients). Patients with mEOC tumours of the infiltrative type are less frequently diagnosed in stage I (12 out of 21) and 2 recurrences were noted out of 12 Stage I patients. Lymph node metastases were not observed in patients with apparent Stage I disease of the expansile type, but were present in 3 out 10 patients with infiltrative disease. Degree of differentiation did not predict recurrence or the presence of lymph node metastases. Prognosis was poor in patients with Stage II or higher disease, irrespective of type of infiltration. CONCLUSIONS: Expansile mEOC is mainly diagnosed in stage I and is not associated with lymph node metastases. Infiltrative mEOC has a worse prognosis and is associated with lymph node metastases. Degree of differentiation was unreliable in predicting recurrence or lymph node metastases.
European journal of cancer (Oxford, England: 1990) 01/2013; · 4.12 Impact Factor
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S E Bojesen,
K A Pooley,
S E Johnatty,
J Beesley,
K Michailidou,
J P Tyrer,
S L Edwards,
H A Pickett,
H C Shen,
C E Smart, [......],
P Hillemanns,
R Winqvist,
M Durst,
P Devilee,
I Runnebaum,
A Jakubowska,
J Lubinski,
A Mannermaa,
R Butzow,
others
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ABSTRACT: TERT-locus SNPs and leukocyte telomere measures are reportedly associated with risks of multiple cancers. Using the Illumina custom genotyping array iCOGs, we analyzed approximately 480 SNPs at the TERT locus in breast (n = 103,991), ovarian (n = 39,774) and BRCA1 mutation carrier (n = 11,705) cancer cases and controls. Leukocyte telomere measurements were also available for 53,724 participants. Most associations cluster into three independent peaks. The minor allele at the peak 1 SNP rs2736108 associates with longer telomeres (P = 5.8 x 10(-7)), lower risks for estrogen receptor (ER)-negative (P = 1.0 x 10(-8)) and BRCA1 mutation carrier (P = 1.1 x 10(-5)) breast cancers and altered promoter assay signal. The minor allele at the peak 2 SNP rs7705526 associates with longer telomeres (P = 2.3 x 10(-14)), higher risk of low-malignant-potential ovarian cancer (P = 1.3 x 10(-15)) and greater promoter activity. The minor alleles at the peak 3 SNPs rs10069690 and rs2242652 increase ER-negative (P = 1.2 x 10(-12)) and BRCA1 mutation carrier (P = 1.6 x 10(-14)) breast and invasive ovarian (P = 1.3 x 10(-11)) cancer risks but not via altered telomere length. The cancer risk alleles of rs2242652 and rs10069690, respectively, increase silencing and generate a truncated TERT splice variant.
01/2013: pages 371-84;
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ABSTRACT: BACKGROUND: Weekly paclitaxel/cisplatin is effective in platinum-resistant epithelial ovarian cancer (EOC). To reduce toxicity, paclitaxel/cisplatin was replaced by paclitaxel/carboplatin. PATIENTS AND METHODS: Patients with progressive EOC after prior 3-weekly paclitaxel/carboplatin were treated with six cycles weekly paclitaxel 90mg/m(2) and carboplatin area under the curve (AUC) 4mg/ml/min, followed by six cycles 3-weekly paclitaxel/carboplatin. End-points were progression free survival (PFS), overall survival (OS), response rate (RR) and toxicity. RESULTS: Median progression free interval after last platinum was 9 (0-81) months in 108 patients; 43 were platinum-resistant, of whom 13 started weekly paclitaxel/carboplatin <6months after progression. During 633 weekly cycles grade 3/4 toxicity included; thrombocytopenia 8%, neutropenia 30%, febrile neutropenia 0.5%. Non-haematologic toxicity was low. Treatment was delayed in 16%, and dose reduced in 2% of cycles. RR was 58% for platinum-resistant and 76% for platinum-sensitive patients, median PFS were 8 (range 1-21) and 13 (1-46) months, median OS 15 (1-69) and 26 (4-93) months, respectively. The 13 platinum-resistant patients with a platinum-therapy free interval <6months had a significant shorter PFS (4 versus 10months, p=0.035) and OS (9 versus 15months, p=0.002). CONCLUSION: Six cycles weekly paclitaxel/carboplatin followed by six 3-weekly cycles is well-tolerated and highly active in platinum-resistant and platinum-sensitive patients.
European journal of cancer (Oxford, England: 1990) 12/2012; · 4.12 Impact Factor
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E I Braicu,
C Fotopoulou,
T Van Gorp,
R Richter,
R Chekerov,
C Hall,
H Butz,
D Cacsire Castillo-Tong,
S Mahner,
R Zeillinger,
N Concin, I Vergote,
J Sehouli
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ABSTRACT: Epithelial ovarian cancer (EOC) is the major cause of death due to gynecological malignancies. The most important prognostic factors are residual tumor mass after surgery and platinum-response. No predictive biomarkers are available to identify patients who will benefit from standard treatment. Aim of our study was to analyse the role of HE4 in predicting surgical and clinical outcome in primary EOC. METHODS: In the European multicentric project "OVCAD", 275 consecutive patients with primary EOC were enrolled. Patients were eligible if radical cytoreductive surgery was performed and platinum-based chemotherapy was applied. Plasma and ascites samples were collected before or during surgery. HE4 and CA125 was determined using ELISA and Luminex technique, respectively. RESULTS: Median age at first diagnosis was 58years (range 18 - 85years). Most patients presented with advanced stage disease, FIGO III or IV (94.6%), grade II-III (96%) and serous histology (86.2%). In most cases a complete cytoreduction to no residual tumor mass was achieved (68.4%). Higher plasma HE4 levels correlated with poor surgery outcome in terms of macroscopically residual tumor mass (p<0.001) and platinum-resistance (p=0.009). Plasma CA125 and the risk index (HE4 and CA125) were independent predictive factor for surgical outcome (p=0.001, OR=3.37, 95%CI=1.61-7.06 and p<0.001, OR=6,041, 95%CI=2.33-15.65, respectively). FIGO stage III was independent predictive factor for platinum response (p=0.039, OR=0.436, 95%CI=0.198-0.960). CONCLUSIONS: The presented data are showing that the combination of HE4 and CA125 expression in plasma might predict the surgical outcome in EOC and by this may have prognostic impact on PFS and OS.
Gynecologic Oncology 11/2012; · 3.89 Impact Factor
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C K Lee,
R J Simes,
C Brown,
V Gebski,
J Pfisterer,
A-M Swart,
D Berton-Rigaud,
M Plante,
T Skeie-Jensen, I Vergote, [......],
J A Ledermann,
E Pujade-Lauraine,
J Bentley,
G Kristensen,
A Belau,
M Nankivell,
U Canzler,
S J Lord,
C Kurzeder,
M Friedlander
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ABSTRACT: Background
Patients with platinum-sensitive recurrent ovarian cancer have variable prognosis and survival. We extend previous work on prediction of progression-free survival by developing a nomogram to predict overall survival (OS) in these patients treated with platinum-based chemotherapy.Patients and methodsThe nomogram was developed using data from the CAELYX in Platinum-Sensitive Ovarian Patients (CALYPSO) trial. Multivariate proportional hazards models were generated based on pre-treatment characteristics to develop a nomogram that classifies patient prognosis based on OS outcome. We also developed two simpler models with fewer variables and conducted model validations in independent datasets from AGO-OVAR Study 2.5 and ICON 4. We compare the performance of the nomogram with the simpler models by examining the differences in the C-statistics and net reclassification index (NRI).ResultsThe nomogram included six significant predictors: interval from last platinum chemotherapy, performance status, size of the largest tumour, CA-125, haemoglobin and the number of organ sites of metastasis (C-statistic 0.67; 95% confidence interval 0.65-0.69). Among the CALPYSO patients, the median OS for good, intermediate and poor prognosis groups was 56.2, 31.0 and 20.8 months, respectively. When CA-125 was not included in the model, the C-statistics were 0.65 (CALYPSO) and 0.64 (AGO-OVAR 2.5). A simpler model (interval from last platinum chemotherapy, performance status and CA-125) produced a significant decrease of the C-statistic (0.63) and NRI (26.4%, P < 0.0001).Conclusions
This nomogram with six pre-treatment characteristics improves OS prediction in patients with platinum-sensitive ovarian cancer and is superior to models with fewer prognostic factors or platinum chemotherapy free interval alone. With independent validation, this nomogram could potentially be useful for improved stratification of patients in clinical trials and also for counselling patients.
Annals of Oncology 10/2012; · 6.43 Impact Factor
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ABSTRACT: In order to ensure that ovarian cancer patients access appropriate treatment to improve the outcome of this disease, accurate characterization before any surgery on ovarian pathology is essential. The International Ovarian Tumor Analysis (IOTA) collaboration has standardized the approach to the ultrasound description of adnexal pathology. A prospectively collected large database enabled both previously developed prediction models like the Risk of Malignancy Index (RMI) to be tested and novel prediction models to be developed and externally validated in order to determine the optimal approach to characterize adnexal pathology preoperatively. The main IOTA prediction models LR1 and LR2 have both shown excellent diagnostic performance (AUCs of 0.96 and 0.95, respectively) and outperform previous diagnostic algorithms. Their test performance almost matches subjective assessment by experienced examiners, which is accepted to be the best way to classify adnexal masses prior to surgery. A two-step strategy using the IOTA simple rules supplemented with subjective assessment of ultrasound findings when the rules do not apply also reached excellent diagnostic performance (sensitivity 90%, specificity 93%) and misclassified fewer malignancies than the RMI. An evidence-based approach to the preoperative characterization of ovarian and other adnexal masses should include the use of LR1, LR2, or IOTA simple rules and subjective assessment by an experienced examiner Copyright © 2012 ISUOG. Published by John Wiley & Sons, Ltd.
Ultrasound in Obstetrics and Gynecology 10/2012; · 3.01 Impact Factor
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M T M van Jaarsveld,
J Helleman,
A W M Boersma,
P F van Kuijk,
W F van Ijcken,
E Despierre, I Vergote,
R H J Mathijssen,
E M J J Berns,
J Verweij,
J Pothof,
E A C Wiemer
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ABSTRACT: Epithelial ovarian cancer is the most lethal gynecological malignancy in the Western world. A major impediment for the successful treatment is the development of drug resistance. The molecular processes that contribute to resistance have been extensively studied; however, there is not much known about regulation by microRNAs (miRNAs). We compared miRNA expression profiles of an isogenic cisplatin-sensitive and -resistant ovarian cancer cell line pair (A2780/A2780 DDP) and found 27 miRNAs to be differentially expressed (2-fold). Five of these, including the family members miR-141/200c, showed a correlation with cisplatin sensitivity in the NCI-60 panel. Overexpression of miR-141 resulted in enhanced resistance to cisplatin in ovarian cancer cell lines. We next correlated the expression level of miR-141 in 132 primary ovarian tumors (108 serous and 24 non-serous) with response to platinum-based chemotherapy. Although no differences were observed in the serous tumors, miR-141 levels were higher in non-serous ovarian tumors that did not respond well to therapy (platinum-free interval <6 months). We demonstrate that miR-141 directly targets KEAP1, and that downregulation of KEAP1 induces cisplatin resistance. Conversely, overexpression of KEAP1 significantly enhanced cisplatin sensitivity. Expression of KEAP1 with its 3'-UTR, and a 3'-UTR in which the miR-141 target site has been mutated, revealed that miR-141 regulates KEAP1 upon exposure to cisplatin. Finally, we show that the NF-κB pathway, which can be regulated by KEAP1, is activated upon miR-141 overexpression, and that inhibition of this pathway partially reverses miR-141-mediated cisplatin resistance. These findings demonstrate that the miR-141-mediated regulation of KEAP1 has a crucial role in the cellular response to cisplatin.Oncogene advance online publication, 8 October 2012; doi:10.1038/onc.2012.433.
Oncogene 10/2012; · 6.37 Impact Factor
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A Lintermans,
A Laenen,
B Van Calster,
M Van Hoydonck,
S Pans,
J Verhaeghe,
R Westhovens,
N L Henry,
H Wildiers,
R Paridaens,
A S Dieudonné,
K Leunen,
L Morales,
K Verschueren,
D Timmerman,
L De Smet, I Vergote,
M R Christiaens,
P Neven
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ABSTRACT: Background
Aromatase inhibitors (AIs) frequently lead to the AI-induced musculoskeletal syndrome (AIMSS). Looking into its pathophysiology, 6 months of AI therapy thickens the tendon sheath with intra-articular fluid (IAF) retention and loss of grip strength. We here report 24-month follow-up data.Patients and methodsA prospective cohort study of 33 postmenopausal breast cancer patients received adjuvant endocrine therapy; 27 received an AI and 6 received tamoxifen. At baseline, 6 and 24 months patients had a rheumatologic examination, including a grip strength test, and magnetic resonance imaging of both hands and wrists. The primary end point was tenosynovial changes; secondary end points were changes in morning stiffness, grip strength and IAF.ResultsTwenty-three AI and 5 tamoxifen patients completed all investigations. Between month 6 and 24, IAF further increased in AI users (P = 0.04) but not in tamoxifen users, and grip strength further decreased in both groups. The worsened tenosynovial changes were strongly correlated with a decrease in grip strength. At 24 months, morning stiffness continued to be present in over a third of AI users.ConclusionAIMSS represents a substantial problem in breast cancer patients. It is associated with tenosynovial changes, IAF retention, joint stiffness and loss of grip strength that do not improve with prolonged use.
Annals of Oncology 10/2012; · 6.43 Impact Factor
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U Wagner,
C Marth,
R Largillier,
J Kaern,
C Brown,
M Heywood,
T Bonaventura, I Vergote,
M C Piccirillo,
R Fossati,
V Gebski,
E P Lauraine
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ABSTRACT: The CALYPSO phase III trial compared CD (carboplatin-pegylated liposomal doxorubicin (PLD)) with CP (carboplatin-paclitaxel) in patients with platinum-sensitive recurrent ovarian cancer (ROC). Overall survival (OS) data are now mature.
Women with ROC relapsing > 6 months after first- or second-line therapy were randomised to CD or CP for six cycles in this international, open-label, non-inferiority trial. The primary endpoint was progression-free survival. The OS analysis is presented here.
A total of 976 patients were randomised (467 to CD and 509 to CP). With a median follow-up of 49 months, no statistically significant difference was observed between arms in OS (hazard ratio = 0.99 (95% confidence interval 0.85, 1.16); log-rank P = 0.94). Median survival times were 30.7 months (CD) and 33.0 months (CP). No statistically significant difference in OS was observed between arms in predetermined subgroups according to age, body mass index, treatment-free interval, measurable disease, number of lines of prior chemotherapy, or performance status. Post-study cross-over was imbalanced between arms, with a greater proportion of patients randomised to CP receiving post-study PLD (68%) than patients randomised to CD receiving post-study paclitaxel (43%; P < 0.001).
Carboplatin-PLD led to delayed progression and similar OS compared with carboplatin-paclitaxel in platinum-sensitive ROC.
British Journal of Cancer 07/2012; 107(4):588-91. · 5.04 Impact Factor
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K Lindemann,
R D Christensen, I Vergote,
G Stuart,
M A Izquierdo,
J Kærn,
H Havsteen,
E Eisenhauer,
M Ridderheim,
A B Lopez,
H Hirte,
E Aavall-Lundquvist,
E Vrdoljak,
J Green,
G B Kristensen
[show abstract]
[hide abstract]
ABSTRACT: Background The addition of anthracyclines to platinum-based chemotherapy may provide benefit in survival in ovarian cancer patients. We evaluated the effect on survival of adding epirubicin to standard carboplatin and paclitaxel. Patients and methods We carried out a prospectively randomized phase III study comparing carboplatin plus paclitaxel (TC; area under the curve 5 and 175 mg/m(2)) with the same combination and epirubicin (TEC; 75 mg/m(2) i.v.). Between March 1999 and August 2001, 887 patients with epithelial ovarian, tubal or peritoneal cancer International Federation of Gynecology and Obstetrics stages IIB-IV were randomized to receive either TC (442 patients) or TEC (445 patients). Results Median time to progression was 16.4 months in the TEC arm and 16.0 months in the TC arm (hazard ratio 0.99; 95% confidence interval [CI]: 0.9-1.2). Median overall survival time was 42.4 months for the TEC arm and 40.2 for the TC arm (hazard ratio 0.96; 95% CI: 0.8-1.1). Grade 3/4 hematologic toxic effects and most grade 3/4 non-hematologic toxic effects were more frequent in the TEC arm. Accordingly, a quality-of-life analysis showed inferiority of TEC versus TC. Conclusion The addition of epirubicin to standard carboplatin and paclitaxel treatment did not improve survival in patients with advanced ovarian, tubal or peritoneal cancer.
Annals of Oncology 04/2012; 23(10):2613-9. · 6.43 Impact Factor
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ABSTRACT: The aims of the study were (1) to increase the limited knowledge on molecular markers contributing to uterine leiomyosarcoma
(LMS) tumorigenesis and (2) to test the ability to predict the clinical course of smooth muscle tumors of low malignancy (SMTLM).
Retrospectively, 2,360 uterine smooth muscle tumors were classified according to the Stanford criteria. After central review,
the clinical course of the SMTLM was traced, and immunohistochemical stainings for p53, p16, p21, Rb, estrogen receptor, progesterone
receptor (PR), cyclin A, cyclin D1, vascular endothelial growth factor, WT-1, and Ki-67 were performed on paraffin-embedded
tissue of the primary tumor and recurrences. On the same tissues, fluorescence in situ hybridization (FISH) analysis was performed
to determine differences in HMGA2, p53, Rb, and 1p36 loci involvement. Five SMTLM were identified, of which two relapsed after 2 and 3years, respectively. Recurrence tumors
were surgically resected, and 3years later, both patients are alive and there is no evidence for progression of disease.
The age at diagnosis in the group with benign course was lower (39, 40, 43years) than that in the group that recurred (48,
53years). Both recurrent SMTLMs expressed less PR and, only quantitatively, more p53. One case expressed more cyclin D1 when
compared to its primary. p16 level was reduced in one recurrent SMTLM. FISH of both SMTLMs that recurred revealed homozygous
deletion of p53 and Rb loci in one of each primary and recurrent tumor. Loss of 1p36 loci was found in both recurrent SMTLMs, and in one case, this genetic imbalance was already present in the primary tumor.
The current data provide evidence that the age at diagnosis of SMTLM is a prognostic factor and that LMS originating from
SMTLM carries an overall better prognosis than primary LMS. Recurrent tumors showed decreased PR levels. Accumulation of genetic
losses, including p53, Rb, and 1p36 loci, may identify a subgroup of SMTLMs with a higher potential towards malignancy.
European Clinics in Obstetrics and Gynaecology 04/2012; 1(3):164-170.
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O Brouckaert,
A Laenen,
J Vanderhaegen,
H Wildiers,
K Leunen,
F Amant,
P Berteloot,
A Smeets,
R Paridaens,
M R Christiaens,
G Floris,
P Moerman,
E Van Limbergen,
S Peeters,
C Weltens, I Vergote,
P Neven
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ABSTRACT: Background Many easily measurable and readily available factors are now established as being prognostic in primary operable breast cancer. We here applied the 2011 St Gallen surrogate definition for breast cancer subclassification using tumor grade instead of Ki67. Patients and methods Four thousand three hundred and eighteen consecutive patients who had surgery for primary operable breast cancer (1 January 2000 and 31 December 2009) in UZ Leuven excluding primary metastastic male breast cancers and those receiving neoadjuvant therapy. Five different surrogate phenotypes were created using the combined expression of estrogen receptor, progesterone receptor, human epidermal growth factor receptor-2 together with tumor grade. Disease-free interval (DFI), distant metastastis-free interval (DMFI), locoregional relapse-free interval (LRRFI), breast cancer-specific survival (BCSS) and overall survival (OS) were calculated. Results Surrogate phenotypes present with significant differences in DFI, DMFI, LRRFI, BCSS and OS. 'Luminal A' tumors presented with the best outcome parameters but the effect weakened at longer follow-up. Conclusions The four surrogate markers, agreed upon by the 2011 St Gallen consensus, defined five prognostic surrogate phenotypes in a large series of consecutively treated breast cancer patients. Their prognostic value changed with longer follow-up. The added value of gene expression profile over classical pathological assessment remains to be defined.
Annals of Oncology 04/2012; 23(10):2578-84. · 6.43 Impact Factor
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K Haest,
A Kumar,
B Van Calster,
K Leunen,
A Smeets,
F Amant,
P Berteloot,
H Wildiers,
R Paridaens,
E Van Limbergen,
C Weltens,
H Janssen,
S Peeters,
J Menten, I Vergote,
B Morlion,
J Verhaeghe,
M R Christiaens,
P Neven
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[hide abstract]
ABSTRACT: We studied the stellate ganglion block (SGB) recently suggested for the treatment of severe vasomotor symptoms and sleep disturbances in breast cancer survivors. Following an initial pilot study, which focused on the acceptability and safety of SGB for this important problem, we evaluated its short- and long-term efficacy. Materials and methods: Postmenopausal breast cancer survivors with severe vasomotor symptoms resistant to standard nonhormonal pharmacological intervention were eligible. Diaries were used to measure daily hot flash scores (frequency and intensity) and sleep quality (Pittsburgh Sleep Quality Index) during scheduled visits at baseline, 1, 4, 12 and 24 weeks following the SGB. Efficacy data were analyzed using longitudinal regression models.
Thirty-four patients participated and none refused the SGB procedure. Most patients received more than one SGB. The pilot study found SGB to be safe. In the main study, hot flash scores were reduced from baseline by 64% [95% confidence interval (CI) -74% to -49%] and 47% (95% CI -62% to -27%) at weeks 1 and 24, respectively. The odds ratio of better sleep quality relative to baseline was 3.4 at week 1 (95% CI 1.6-7.2) and 4.3 at week 24 (95% CI 1.9-9.8).
In the short term, SGB appears to be an effective treatment with acceptable morbidity for some breast cancer survivors with therapy-resistant vasomotor symptoms and/or sleep disturbances. Although sleep quality was maintained out to 24 weeks the efficacy of SGB for hot flashes was reduced over time. A randomized controlled trial is needed to confirm these findings.
Annals of Oncology 03/2012; 23(6):1449-54. · 6.43 Impact Factor
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ABSTRACT: To compare guidelines from the Royal College of Obstetricians and Gynaecologists (RCOG) based on the Risk of Malignancy Index (RMI) with a protocol based on logistic regression model LR2 developed by the International Ovarian Tumour Analysis (IOTA) group for triaging women with an ovarian mass as low, moderate, or high risk of malignancy.
Observational diagnostic study conducted between 2005 and 2007 at 21 oncology referral centres, referral centres for ultrasonography and general hospitals.
In all, 1938 women undergoing surgery for an ovarian mass.
RCOG guidelines use the RMI to triage women as low (RMI < 25), moderate (25-250), or high (above >250) risk. The IOTA protocol uses LR2s estimated probability of malignancy (<0.05 indicates low risk, ≥ 0.05 but <0.25 moderate risk, and ≥ 0.25 high risk).
Percentages of benign, borderline and invasive tumours classified as low, moderate or high risk.
The IOTA and RCOG protocols classified 71.1% and 62.1% of benign tumours as low risk, respectively (difference 9.0; 95% CI 6.2-11.9, P < 0.0001). Of invasive tumours, 88.6% and 73.6% were labelled high risk (difference 15.0; 10.6-19.4, P < 0.0001), and 3.0% and 5.2% were labelled low risk (difference -2.2; -4.6 to 0.2, P = 0.07) respectively by each protocol. Similar results were found after stratification for menopausal status.
The IOTA protocol was more accurate for triage than the RCOG protocol. The IOTA protocol would avoid major surgery for more women with benign tumours while still appropriately referring more women with an invasive tumour to a gynaecological oncologist.
BJOG An International Journal of Obstetrics & Gynaecology 03/2012; 119(6):662-71. · 3.41 Impact Factor
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ABSTRACT: Although most patients with advanced gynaecologic malignancies respond to first-line treatment with platinum-taxane doublets, a significant proportion of patients relapse. Combining targeted agents that have non-overlapping mechanisms of action with chemotherapy may potentially increase the disease-free interval. Accordingly, this study evaluated the feasibility of combining pazopanib, an oral angiogenesis inhibitor, with paclitaxel and carboplatin.
This open-label, phase I/II study planned to evaluate the safety and efficacy of paclitaxel 175 mg m(-2) plus carboplatin (AUC5 (Arm A) or AUC6 (Arm B)) once in every 3 weeks for up to six cycles with either 800 or 400 mg per day pazopanib.
Dose-limiting toxicities (DLTs) were observed in two of the first six patients enrolled at pazopanib 800 mg plus paclitaxel 175 mg m(-2) plus carboplatin AUC5. Of the six patients enrolled in the next and lowest dosing level planned in the study, pazopanib 400 mg plus paclitaxel 175 mg m(-2) plus carboplatin AUC5, two patients also experienced DLTs and the study was terminated. Two of the 4 DLTs observed overall were gastrointestinal perforations. Severe myelotoxicity was reported in 6 of 12 patients.
Combining either 800 or 400 mg per day pazopanib with standard carboplatin/paclitaxel chemotherapy is not a feasible treatment option.
British Journal of Cancer 02/2012; 106(4):629-32. · 5.04 Impact Factor
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J Alexandre,
C Brown,
D Coeffic,
N Raban,
J Pfisterer,
J Mäenpää,
H Chalchal,
B Fitzharris,
B Volgger, I Vergote,
C Pisano,
A Ferrero,
E Pujade-Lauraine
[show abstract]
[hide abstract]
ABSTRACT: 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.
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.
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.
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.
British Journal of Cancer 02/2012; 106(4):633-7. · 5.04 Impact Factor
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S Bondong,
H Kiefel,
T Hielscher,
A G Zeimet,
R Zeillinger,
D Pils,
E Schuster,
D C Castillo-Tong,
I Cadron, I Vergote,
I Braicu,
J Sehouli,
S Mahner,
M Fogel,
P Altevogt
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ABSTRACT: Overexpression of L1-cell adhesion molecule (L1CAM) has been observed for various carcinomas and correlates with poor prognosis and late-stage disease. In vitro, L1CAM enhances proliferation, cell migration, adhesion and chemoresistance. We tested L1CAM and interleukin-1 beta (IL-1β) expression in tumor samples and ascitic fluid from ovarian carcinoma patients to examine its role as a prognostic marker.
We investigated tumor samples and ascitic fluid from 232 serous ovarian carcinoma patients for L1CAM by enzyme-linked immunosorbent assay. L1CAM expression was correlated with pathoclinical parameters and patients' outcome. IL-1β levels were measured in tumor cell lysates. Ovarian cancer cell lines were analyzed for the contribution of L1CAM to IL-1β production and nuclear factor 'kappa-light-chain-enhancer' of activated B-cells (NF-κB) activation.
We observed that L1CAM-expressing tumors show a highly invasive phenotype associated with restricted tumor resectability at primary debulking surgery and increased lymphogenic spread. Soluble L1CAM proved to be a marker for poor progression-free survival and chemoresistance. In ovarian carcinoma cell lines, the specific knock-down of L1CAM reduces IL-1β expression and NF-κB activity.
L1CAM expression contributes to the invasive and metastatic phenotype of serous ovarian carcinoma. L1CAM expression and shedding in the tumor microenvironment could contribute to enhanced invasion and tumor progression through increased IL-1β production and NF-κB activation.
Annals of Oncology 01/2012; 23(7):1795-802. · 6.43 Impact Factor
