Predictors of the use of complementary and alternative medicine (CAM) by women at high risk for breast cancer

BackgroundFew data exist regarding the use of complementary and alternative medicine (CAM) by unaffected women at high risk of breast cancer.MethodsSelf-reported CAM use by women from multiple-case breast cancer families was obtained by questionnaire. Factors associated with CAM use were assessed using multiple logistic regression.ResultsOf 892 women, 55% (n = 489) used CAM, 6% (n = 53) specifically to prevent cancer. CAM use was independently associated with tertiary education level (OR 2.56, 95% CI 1.83–3.58, p < 0.001), greater physical activity (OR 1.05 per hour of physical activity/week, 95% CI 1.00–1.10, p = 0.049), greater anxiety (OR 1.92, 95% CI 1.16–3.16, p = 0.01), not currently smoking (OR 0.64, 95% CI 0.42–0.97, p = 0.037) and lower perceived BC risk (OR 0.82 per 20 percentage points, 95% CI 0.72–0.94, p = 0.005).ConclusionsThe majority of high-risk women use CAM, but mostly for reasons other than cancer prevention. Most predictors of CAM use are consistent with the limited literature for women at high risk for cancer.     

The efficacy of zoledronic acid in breast cancer adjuvant therapy: a meta-analysis of randomised controlled trials

BackgroundThe effect of zoledronic acid in breast cancer adjuvant therapy concerning improvement of patient survival has yet to be confirmed. We performed a meta-analysis of published and unpublished randomised controlled trials with the aim of accurate evaluation between clinical outcome and the association of the addition of zoledronic acid to adjuvant therapy.MethodsWe searched PubMed (from 1966 to present) and online abstracts from the proceeding Annual Meetings of the American Society of Clinical Oncology (ASCO) (years 1992–2010) and online abstracts from San Antonio Breast Cancer Symposium (years 2004–2010). A total of five eligible studies including 3676 subjects and 3678 controls met our search criteria and were evaluated. Random and fixed-effects meta-analytical models were used where indicated, and between-study heterogeneity was assessed. The primary study end-points were the disease free survival (DFS). Secondary end-points were overall survival (OS), distant or loco-regional recurrence free survival and bone metastasis free survival.FindingsCompared with the control arm, adjuvant breast cancer treatment with zoledronic acid did not significantly improve overall survival, disease free survival, bone metastasis free survival, distant and locoregional recurrence free survival. However, in the postmenopausal subgroup, the addition of zoledronic acid to standard therapy could significantly improve DFS (relative risk (RR) = 0.763, 95% confidence interval (CI) 0.658–0.884, p < 0.001) and reduce the risk of distant (RR = 0.744, 95% CI 0.611–0.906, p = 0.003) and locoregional recurrence (RR = 0.508, 95% CI 0.340–0.760, p = 0.001).InterpretationAdjuvant zoledronic acid did not significantly improve the prognosis of breast cancer patients. Due to the highly variable definitions of menopause utilised in different studies, we hypothesise that zoledronic acid may have a potential effect on postmenopausal patients. Additional studies are needed to evaluate the value of adjuvant treatment of zoledronic acid in premenopausal counterparts, differing disease stages and various pathological types of breast cancer.     

Alterations in the p53 pathway and prognosis in advanced ovarian cancer: a multi-factorial analysis of the EORTC Gynaecological Cancer group (study 55865)

PurposeThe study was designed to determine independent prognostic variables in suboptimally debulked advanced ovarian cancer patients entered in the randomised phase III study EORTC 55865.Experimental designRetrospectively collected paraffin blocks from 169 patients with stages IIb–IV epithelial ovarian cancer, taken at primary debulking surgery, were analysed. All patients were treated with cyclophosphamide and cisplatin (CP), and followed up for a median of 10 years. Expression of p53, bcl-2, P21, Ki-67 and HER-2 status was assessed by immunohistochemistry (IHC).ResultsExpression of p21, a downstream effector of the p53 gene, was found to be a favourable prognostic factor for survival (HR 0.58, CI 0.36–0.94, p = 0.025) in addition to FIGO stage (HR 1.54, CI 1.08–2.21, p = < 0.02). For progression free survival (PFS), both p21 (HR 0.52) and Ki-67 (HR 0.6) were significant factors.ConclusionP21 overexpression is a positive prognostic factor for survival and PFS in advanced ovarian carcinoma with residual lesions of more than 1 cm.     

Gemcitabine versus gemcitabine plus dalteparin thromboprophylaxis in pancreatic cancer

BackgroundAnnualised figures show an up to 7-fold higher incidence of vascular thromboembolism (VTE) in patients with advanced pancreatic cancer (APC) compared to other common malignancies. Concurrent VTE has been shown to confer a worse overall prognosis in APC.MethodsOne hundred and twenty three APC patients were randomised to receive either gemcitabine 1000 mg/m² or the same with weight-adjusted dalteparin (WAD) for 12 weeks. Primary end-point was the reduction of all-type VTE during the study period. NCT00462852, ISRCTN: 76464767.FindingsThe incidence of all-type VTE during the WAD treatment period (<100 days from randomisation) was reduced from 23% to 3.4% (p = 0.002), with a risk ratio (RR)of 0.145, 95% confidence interval (CI) (0.035–0.612) and an 85% risk reduction. All-type VTE throughout the whole follow-up period was reduced from 28% to 12% (p = 0.039), RR = 0.419, 95% CI (0.187–0.935) and a 58% risk reduction. Lethal VTE <100 days was seen only in the control arm, 8.3% compared to 0% (p = 0.057), RR = 0.092, 95% CI (0.005–1.635).InterpretationWeight adjusted dalteparin used as primary prophylaxis for 12 weeks is safe and produces a highly significant reduction of all-type VTE during the prophylaxis period. The benefit is maintained after dalteparin withdrawal although decreases with time.     

The risk of skin rash and stomatitis with the mammalian target of rapamycin inhibitor temsirolimus: a systematic review of the literature and meta-analysis

ObjectiveWe conducted a systematic review of the literature and performed a meta-analysis to determine the risk of developing skin rash and stomatitis among patients receiving temsirolimus.MethodsDatabases from PubMed and Web of Science from January, 1998 until June, 2011 and abstracts presented at the American Society of Clinical Oncology annual meetings from 2004 through 2011 were searched to identify relevant studies. The incidence and relative risk (RR) of skin rash and stomatitis were calculated using random-effects or fixed-effects model depending on the heterogeneity of included studies.ResultsA total of 779 patients from 10 clinical trials were included in this analysis. The overall incidence of all-grade rash was 45.8% (95% confidence interval (CI): 35.6–56.3%), with a RR of 7.6 (95% CI: 4.4–13.3; p < 0.001). The overall incidence of high-grade rash was 3.3% (95% CI: 1.9–5.6%), with a RR of 13.70 (95% CI: 0.82–227.50, p = 0.07). The overall incidence of all-grade stomatitis was 44.3% (CI: 32.1–57.1%), with a RR of 11.10, 95% CI: 5.60–22.00; p < 0.001). The overall incidence of high-grade stomatitis was 3.2% (95% CI: 1.9–5.4%), with a RR of 13.2 (95% CI: 0.80–218.50, p = 0.07).ConclusionThere is a significant risk of developing skin rash and stomatitis in cancer patients receiving temsirolimus. The risk is independent of underlying tumour. Adequate monitoring and early intervention are recommended to prevent debilitating toxicity and suboptimal dosing.     

Lack of TIMP-1 tumour cell immunoreactivity predicts effect of adjuvant anthracycline-based chemotherapy in patients (n = 647) with primary breast cancer. A Danish Breast Cancer Cooperative Group Study

PurposeA number of prospective studies have shown that adjuvant CEF significantly improves disease-free and overall survival as compared to CMF in breast cancer patients. Our aim was to determine whether the benefit of epirubicin versus methotrexate differs according to TIMP-1 tumour cell immunoreactivity.Experimental designTissue micro arrays from 647 patients randomly assigned to CMF or CEF in DBCG trial 89D were included. The primary end-point was invasive disease-free survival (IDFS). A central assessment of tissue inhibitor of metalloproteinases 1 (TIMP-1) status was performed using immunohistochemistry (IHC). Tumours were regarded as TIMP-1 positive if epithelial breast cancer cells were stained using the anti-TIMP-1 monoclonal antibody VT7.ResultsBy central assessment 75% of tumours were classified as tumour cell TIMP-1 positive. Among CEF-treated patients, individuals with TIMP-1 negative tumours had a significant longer IDFS than patients with TIMP-1 positive tumours (p = 0.047). The multivariate Cox regression analysis of IDFS showed that CEF was superior to CMF among patients with TIMP-1 negative tumours (hazard ratio (HR) = 0.51; 95% confidence interval (CI): 0.31–0.84, p = 0.0085), while no significant difference could be demonstrated among patients with TIMP-1 positive tumours (HR = 0.88; 95% CI: 0.68–1.13, p = 0.32). A non-significant TIMP-1 status (positive or negative) versus treatment (CMF or CEF) interaction was detected for IDFS (p = 0.06) and OS (p = 0.21).ConclusionLack of TIMP-1 tumour cell immunoreactivity seems to predict a favourable effect of epirubicin-containing adjuvant therapy in primary breast cancer. However, an independent study is awaited to validate the potential predictive value of TIMP-1 immunoreactivity.     

ERG protein expression reflects hormonal treatment response and is associated with Gleason score and prostate cancer specific mortality

BackgroundERG (ETS regulated gene) protein expression has been shown to reflect ERG genomic rearrangements in prostate cancer (PCA). However, ERG protein expression prognostic value has not been yet investigated.DesignERG protein expression was investigated in a cohort of 312 men with PCA diagnosed in transurethral resection of the prostate.ResultsERG expression was detected in 76/293 (25.9%) of patients. Overall ERG expression was associated with Gleason score (GS) (p < 0.0001), tumour volume (p = 0.04) and with cancer specific mortality (p = 0.15). Low ERG intensity was significantly associated with higher GS (p = 0.02) and marginally with cancer specific mortality (p = 0.11). The association with caner specific mortality was more significant in patients without any hormonal manipulation (p = 0.02). Multivariate Cox model using GS, tumour volume and ERG intensity to predict time to cancer specific death yielded a marginally significant effect for high versus low ERG protein expression (hazard ratio (HR) = 0.36; 95% confidence interval (CI): 0.10–1.38; p = 0.14) and a non-significant effect for GS >7 (HR = 4.85; 95% CI: 0.48, 48.65; p = 0.18). Men with ERG expression showed longer free progression time to castration resistant disease compared to men with no ERG expression (mean 11.39 versus 6.1 months, p = 0.08).ConclusionWe report significant association between ERG protein levels and each of GS, progression to castration resistant and cancer specific mortality. High ERG intensity was associated with lower GS, better overall survival and longer free progression times to castration resistant disease. ERG protein levels may have prognostic and therapeutic role in PCA and should be investigated in future studies.     

Primary versus secondary cytoreduction for epithelial ovarian cancer: a paired analysis of tumour pattern and surgical outcome

ObjectiveRecurrence rates of Epithelial Ovarian Cancer (EOC) remain high. Aim of the present study was to compare tumour pattern and surgical outcome at primary and secondary tumourdebulking in a paired patients’ collective.MethodsSeventy-nine consecutive EOC-patients who underwent both primary and secondary cytoreduction in our institution between 09/2000 and 12/2010 were evaluated according to a validated documentation-tool (‘IMO’, Intraoperative Mapping Ovarian Cancer). Differences in tumour-pattern between paired samples were examined using McNemar-test or sign-test.ResultsA complete macroscopic tumour resection could be achieved significantly more often during primary versus secondary surgery (77% versus 50%; p < 0.001) in comparable operative times (242 min versus 199 min; p = 0.15) and by equivalent operative morbidity (25% versus 29%; p = 0.424). Tumour-residuals at primary correlated significantly with tumour-residuals at secondary cytoreduction (p = 0.003). Patients at relapse had significantly higher rates of tumour involvement of the gastric serosa (2.5% versus 16.9%; p = 0.001), serosa of small intestine (20.3% versus 44.9%; p < 0.001) and mesentery (30.4% versus 50%; p = 0.012). The relative-risk for peritoneal carcinosis, intestinal tumour involvement or positive lymph nodes at secondary tumourdebulking in the case of presence of these features at primary surgery was 1.53 (95% CI: 0.89–2.63); 0.92 (95% CI: 0.65–1.31) and 1.49 (95% CI: 0.83–2.68), respectively, and thus not reaching a statistical significance.ConclusionsSecondary cytoreduction due to EOC appears to be associated with significantly lower optimal tumourdebulking rates compared to primary setting, since the disease tends to recur in patterns less accessible to complete resection such as gastrointestinal serosa, mesentery and upper abdomen. By maximal surgical effort, tumour residuals significantly correlate between primary and secondary cytoreduction. No other predictors of surgical outcome or tumour-pattern could be identified.     

Role of cardioprotective therapy for prevention of cardiotoxicity with chemotherapy: A systematic review and meta-analysis

BackgroundCardiotoxicity is a well-recognised complication of chemotherapy with anthracycline and/or trastuzumab, and its prevention remains an important challenge in cancer survivorship. Several successful preventative strategies have been identified in animal trials. We sought to assemble the clinical evidence that prophylactic pharmacological interventions could prevent left ventricular (LV) dysfunction and heart failure in patients undergoing chemotherapy.MethodsWe undertook a systemic review of the evidence from randomised trials and observational studies where a prophylactic intervention was compared with a control arm in patients with a normal ejection fraction and no past history of heart failure. The primary outcome was development of heart failure (HF), a drop in ejection fraction (EF) or both. A random-effects model was used to combine relative risks (RR) and 95% confidence intervals (CIs), and a meta-regression was undertaken to assess the impact of potential covariates.FindingsData were collated from 14 published articles (n = 2015 paediatric and adult patients) comprising 12 randomised controlled trials and two observational studies. The most studied chemotherapeutic agents were anthracyclines, and prophylactic agents included dexrazoxane, statins, beta-blocker and angiotensin antagonists. There were 304 cardiac events in the control arm compared to 83 in the prophylaxis arm (RR = 0.31 [95% CI: 0.25–0.39], p < 0.00001). Cardiac events were reduced with dexrazoxane (RR = 0.35 [95% CI 0.27–0.45], p < 0.00001), beta-blockade (RR = 0.31 [95% CI 0.16–0.63], p = 0.001), statin (RR = 0.31 [95% CI 0.13–0.77], p = 0.01) and angiotensin antagonists (RR = 0.11 [95% CI 0.04–0.29], p < 0.0001).InterpretationProphylactic treatment with dexrazoxane, beta-blocker, statin or angiotensin antagonists appear to have similar efficacy for reducing cardiotoxicity.     

Substantial increase in the use of adjuvant systemic treatment for early stage breast cancer reflects changes in guidelines in the period 1990-2006 in the southeastern Netherlands

BackgroundThis study evaluated trends in adjuvant systemic treatment among breast cancer patients and analyzed the factors on which treatment choice was based.Patients and methodsPatients diagnosed with early stage breast cancer in 1990–2006 were selected from the registry of the Comprehensive Cancer Centre South (n = 8261). The probability of receiving therapy was determined per characteristic for the periods 1990–1997, 1998–2001 and 2002–2006, separately.ResultsThe use of any adjuvant systemic treatment increased from 37% in 1990–1997 to 51% in 1998–2001 and 53% in 2002–2006 (p for trend < 0.0001). In the period 1990–1997, lymph node status (positive vs. negative: probability ratio (PR = 25.8; 95% CI, 16.5–40.4) and age (⩾ 60 vs. ⩽ 35 years: PR = 0.01; 95% CI, 0.00–0.02) were the main determinants of the likelihood of receiving chemotherapy. From 1998 onwards, age remained the most important factor in decreasing the likelihood of receiving chemotherapy. During 1990–1997 the use of hormonal therapy was mainly determined by positive lymph node status (PR = 35; 95% CI, 25–49) and age (⩾ 70 vs. ⩽ 35 years: PR = 9.3; 95% CI, 4.4–20), whereas positive hormone receptor status mainly affected hormonal therapy use (PR = 17; 95% CI, 10–28) in the period 2002–2006. Marked differences were observed between hospitals in the adoption of adjuvant systemic treatment for node–negative patients.ConclusionsThe impact of patient and tumour characteristics on treatment choice varied over time, reflecting major changes in the Dutch treatment guidelines. Patients older than 70 years received almost no chemotherapy.     

Subjective assessment by ultrasound is superior to the risk of malignancy index (RMI) or the risk of ovarian malignancy algorithm (ROMA) in discriminating benign from malignant adnexal masses

PurposeThe combination of two tumour markers, CA125 and HE4, in the risk of ovarian malignancy assay (ROMA) has been shown to be successful in classifying patients into those who have a high or low risk of epithelial ovarian cancer. In the present study, the diagnostic accuracy of ROMA was assessed and compared to the diagnostic accuracy of the two most widely used ultrasound methods, namely the risk of malignancy index (RMI) and subjective assessment by ultrasound.MethodsFrom August, 2005 to March, 2009, 432 women with a pelvic mass who were scheduled to have surgery were enrolled in a single-centre prospective cohort study. A preoperative ultrasound was performed and preoperative CA125 and HE4 serum levels were measured. Once the final surgical pathology reports were obtained, the diagnostic accuracy and performance indices of ROMA, RMI and subjective assessment were calculated.ResultsOf the 432 eligible patients, 374 could be analysed. Subjective assessment had the highest area under the receiver operator characteristic curve (AUC) (0.968, 95% CI:0.945–0.984), followed by the RMI (0.931, 95% CI:0.901–0.955). The subjective assessment and RMI both had significantly higher AUCs than the ROMA (0.893, 95% CI:0.857–0.922; P < 0.0001 and P = 0.0030, respectively). The pre- and postmenopausal populations generated similar results.ConclusionAlthough new tumour markers models are promising, they do not contribute significantly to the diagnosis of ovarian cancer. Ultrasound, especially subjective assessment by ultrasound, remains superior in discriminating malignant from benign ovarian masses.     

Prognostic evaluation of tumour type and other histopathological characteristics in advanced epithelial ovarian cancer, treated with surgery and paclitaxel/carboplatin chemotherapy: cell type is the most useful prognostic factor

AimOvarian carcinomas have been classified into types I and II according to the hypothesised mode of carcinogenesis and molecular characteristics. The prognostic significance of this classification has not been studied.Patients and methodsFive hundred and sixty-eight patients with histologically confirmed, ovarian, fallopian tube or peritoneal carcinomas, international federation of gynecology and obstetrics (FIGO) stages IIC–IV, treated with paclitaxel/platinum following cytoreductive surgery, were included in this analysis. Type I included low-grade serous, mucinous, endometrioid and clear-cell and type II high-grade serous, unspecified adenocarcinomas and undifferentiated carcinomas.ResultsMedian overall survival (OS) was 49 months for type I versus 45 for type II (p = 0.576). In contrast to type II, there was considerable prognostic heterogeneity among the subtypes included in type I. Cox regression analysis showed that cell-type classification: low-grade serous, mucinous, endometrioid, clear-cell, type II (high-grade serous, unspecified adenocarcinomas, undifferentiated carcinoma) was an independent predictor of survival (respective median OS 121 versus 15 versus 64 versus 29 versus 45 months, p = 0.003). On the contrary, histopathological subtype or tumour type (I versus II) did not offer additional prognostic information.ConclusionThe proposed model of ovarian tumourigenesis does not reflect tumour behaviour in advanced disease. Tumour-cell type is the most relevant histopathological prognostic factor in advanced ovarian cancer treated with platinum/paclitaxel.     

The incidence and relative risk of cardiovascular toxicity in patients treated with new hormonal agents for castration-resistant prostate cancer

AimNew hormonal agents are available for treating metastatic castration-resistant prostate cancer (mCRPC). We aim to define the incidence and relative risk (RR) of cardiovascular events in mCRPC patients treated with these agents.MethodsProspective studies were identified by searching the MEDLINE/PubMed, Cochrane Library and ASCO Meeting abstracts. Combined relative risks (RRs) and 95% confidence intervals (CIs) were calculated using fixed- or random-effects methods.ResultsWe included six articles in this meta-analysis covering a total of 6735 patients who were used to evaluate cardiac toxicity. The use of new hormonal agents was associated with an increased risk of all grades of such toxicity (RR = 1.32, 95% CI, 1.08–1.60; p = 0.006) compared to a placebo, even if the absolute difference in terms of incidence was small at 14.8% versus 11.5%, respectively. No increased risk of grade 3–4 events (RR = 1.35, 95% CI, 0.90–2.03; p = 0.15) was observed.A total of 7830 patients were used to evaluate hypertension, and it was found that the use of new hormonal agents compared to a placebo was associated with an increased risk of all-grades (RR = 1.84, 95% CI, 1.37–2.46; p < 0.001) and grade 3–4 events (RR = 1.77, 95% CI, 1.13–2.77; p = 0.01). The absolute incidence was 12.5% versus 7.5% for all-grades and 3.7% versus 2.4% for grade 3–4.ConclusionsThis analysis revealed a significant increase in the incidence and RR of cardiovascular toxicity in mCRPC treated with new hormonal agents as opposed to a placebo, even though the occurrence of all- and grade 3–4 events rose only 14% and 4%, respectively. Follow-ups for the onset of treatment-related cardiovascular events should therefore be considered in these patients.     

Plasminogen activator inhibitor-1 promoter polymorphism is not associated with the aggressiveness of disease in prostate cancer

AimsPAI-1 (plasminogen activator inhibitors-1) regulates plasminogen activation, and is related to tumour development. This study aims to test whether the promoter polymorphism in the PAI-1 gene is related to the aggressiveness of disease in prostate cancer.Materials and methodsIn the present study, Taqman SNP genotyping assay was used to detect PAI-1 4G/5G polymorphism in DNA from paraffin-embedded tissues of 98 Caucasian patients with prostate cancer.ResultsThe distribution of the genotypes is in Hardy–Weinberg equilibrium. The genotype had no statistically significant relationship with other prognostic factors. Similar risks for recurrence were seen in individuals with the 4G/4G and 4G/5G genotypes compared to those with 5G/5G genotype (odds ratio [OR] 2.65, 95% CI: 0.41–16.94, P = 0.30; OR = 2.19, 95% CI: 0.38–12.49, P = 0.38).ConclusionWe concluded that PAI-1 promoter polymorphism is not associated with the aggressiveness of disease in prostate cancer.     

Infusion of calcium and magnesium for oxaliplatin-induced sensory neurotoxicity in colorectal cancer: a systematic review and meta-analysis

BackgroundIt is hypothesised that infusion of calcium and magnesium (Ca/Mg) can reduce the occurrence of oxaliplatin-related sensory neurotoxicity. However, more recent data have drawn a controversial picture concerning this topic.MethodsA comprehensive literature search was performed using Medline, Embase, Cochrane Library and Google Scholar database up to 1st August 2011. Keywords for the search were: calcium, magnesium and oxaliplatin. The odd ratio (OR) for neurotoxicity and relative risk (RR) for tumour response rate were calculated.ResultsSeven studies (four randomised controlled trials (RCTs) and three cohorts) including a total of 1238 participants met our criteria. Meta-analysis of three RCT studies that reported in National Cancer Institute-Common Toxicity Criteria (NCE-CTC) showed that OR for neurotoxicity of Grade ⩾2 was not significant (OR 0.47; 95% confidence interval (CI) 0.22–1.00, P homogeneity = .729). The OR was also not significant in All Grades (OR 3.15, 0.32–31.35, P homogeneity = .952) and Grade 3 subgroup (OR 1.64, 0.30–9.00, P homogeneity = .656). No statistically significant difference was observed in RR for tumour response rate. (RR = 0.91, 0.78–1.06, P homogeneity = .33)ConclusionsThis meta-analysis does not support the hypothesis that infusion of Ca/Mg reduces the occurrence of neurotoxicity in oxaliplatin-treated patients with colorectal cancer measuring with NCE-CTC criteria. On the other hand, our results support the hypothesis that administrations of Ca/Mg do not impair the efficacy of oxaliplatin-based chemotherapy. However, large-scale randomised, controlled clinical trials will be required to confirm these hypotheses.     

Association of galectin-3 expression with melanoma progression and prognosis

AimsGalectin-3 plays an important role in adhesion, proliferation, differentiation, angiogenesis and metastasis in multiple tumours. To investigate the role of galectin-3 in melanoma pathogenesis we examined the expression of galectin-3 in melanocytic lesions and analysed the correlation between galectin-3 expression and clinicopathologic factors including patient survival and BRAF mutation status.MethodsWe evaluated the expression of galectin-3 in 53 cases of benign naevi, 31 cases of dysplastic naevi, 59 in-situ melanomas, 314 cases of primary melanoma and 69 metastatic melanomas using tissue microarray and immunohistochemistry.ResultsMarked differences in expression of galectin-3 were seen between different categories of melanocytic lesions (ANOVA p < 0.0001). An increase in expression of galectin-3 between benign naevi and thin primary melanomas and a progressive decrease in expression between thin primary melanomas and thicker melanomas or metastatic melanomas was seen. Strong galectin-3 expression was associated with improved overall survival (p = 0.002 and p = 0.0002 for cytoplasmic and nuclear expression, respectively) and melanoma-specific survival (p = 0.017 and p = 0.003 for cytoplasmic and nuclear expression, respectively). A multifactorial Cox regression analysis suggested that galectin-3 expression was an independent prognostic marker for overall survival in melanoma (risk ratio 0.73, 95% CI 0.547–0.970, p = 0.031 for cytoplasmic expression and risk ratio 0.76, 95% CI 0.587–0.985, p = 0.036 for nuclear expression). No association between galectin-3 expression and BRAF mutation status was observed.ConclusionThis study suggests that galectin-3 is a marker of progression in melanocytic lesions and a novel prognostic marker in primary melanoma.     

Prognostic impact of the time interval between surgery and chemotherapy in advanced ovarian cancer: Analysis of prospective randomised phase III trials

Background and AimsSurgery followed by platinum-taxane chemotherapy is the current standard approach to treat advanced ovarian cancer. The impact of the time interval between surgery and initiation of chemotherapy for clinical outcome has not been clarified yet.MethodsIndividual patient data analysis of 3326 patients from three prospective randomised phase III trials conducted between 1995 and 2002 to investigate platinum-taxane based chemotherapy regimens in advanced ovarian cancer. Time to chemotherapy (TTC) was analysed and correlated with outcome.ResultsMedian TTC was 19 days (range 1–56). The effect of TTC differed significantly for patients with or without residual disease for progression-free (PFS; interaction p = 0.004) and for overall survival (OS; interaction p = 0.028). A delayed start of chemotherapy was associated with earlier disease recurrence (HR 1.038, 95% CI 0.973; 1.106, p = 0.257 per week delay) and a significantly decreased OS (HR 1.087, 95% CI 1.005; 1.176 p = 0.038) in patients with no residual tumour after surgery. In contrast, in patients with residual disease, a longer TTC was significantly associated with later progression (HR 0.931, 95% CI 0.895; 0.969, p < 0.001) and no effect towards OS (HR 0.983, 95% CI 0.940; 1.028, p = 0.452).ConclusionsOur results provide evidence that early initiation of chemotherapy might result in slightly improved survival in patients with complete cytoreduction while patients with residual disease after surgery did not benefit from earlier chemotherapy. A prospective study randomising patients to different time intervals could clarify the definitive relevance of the time between surgery and chemotherapy.     

Local recurrence following breast-conserving treatment in women aged 40 years or younger: Trends in risk and the impact on prognosis in a population-based cohort of 1143 patients

AimTo evaluate trends in the risk of local recurrences after breast-conserving treatment (BCT) and to examine the impact of local recurrence (LR) on distant relapse-free survival in a large, population-based cohort of women aged ?40 years with early-stage breast cancer.MethodsAll women (n = 1143) aged ?40 years with early-stage (pT1-2/cT1-2, N0-2, M0) breast cancer who underwent BCT in the south of the Netherlands between 1988 and 2010 were included. BCT consisted of local excision of the tumour followed by irradiation of the breast.ResultsAfter a median follow-up of 8.5 (0.1–24.6) years, 176 patients had developed an isolated LR. The 5-year LR-rate for the subgroups treated in the periods 1988–1998, 1999–2005 and 2006–2010 were 9.8% (95% confidence interval (CI) 7.1–12.5), 5.9% (95% CI 3.2–8.6) and 3.3% (95% CI 0.6–6.0), respectively (p = 0.006). In a multivariate analysis, adjuvant systemic treatment was associated with a reduced risk of LR of almost 60% (hazard ratio (HR) 0.42; 95% CI 0.28–0.60; p < 0.0001). Patients who experienced an early isolated LR (?5 years after BCT) had a worse distant relapse-free survival compared to patients without an early LR (HR 1.83; 95% CI 1.27–2.64; p = 0.001). Late local recurrences did not negatively affect distant relapse-free survival (HR 1.24; 95% CI 0.74–2.08; p = 0.407).ConclusionLocal control after BCT improved significantly over time and appeared to be closely related to the increased use and effectiveness of systemic therapy. These recent results underline the safety of BCT for young women with early-stage breast cancer.     

Primary treatment and prognostic factors of small cell neuroendocrine carcinoma of the uterine cervix: a Taiwanese Gynecologic Oncology Group study

BackgroundOur aims were to investigate the treatment and clinicopathological variables in relation to prognosis in small cell neuroendocrine cervical carcinoma (SCNECC).Patients and methodsClinical data of SCNECC patients with International Federation of Gynaecology and Obstetrics (FIGO) stages I–IV treated between 1987 and 2009 at member hospitals of the Taiwanese Gynecologic Oncology Group (TGOG) were retrospectively reviewed.ResultsOf the 179 eligible patients, 104 were of FIGO stage I, 19 stage IIA, 23 stage IIB, 9 stage III, and 24 stage IV. The median failure-free survival (FFS) was 16.0 months, and the median cancer-specific survival (CSS) was 24.8 months. In multivariate analysis, FIGO stage and lymph node metastasis were selected as independent variables in stages I–IV. In stages IIB–IVB, primary treatment containing etoposide and platinum for at least 5 cycles (EP5+) (n = 16) was associated with significantly better 5-year FFS (42.9% versus 11.8%, p = 0.041) and CSS (45.6% versus 17.1%, p = 0.035) compared to other treatments (n = 40). Furthermore, concurrent chemoradiation with EP5+ (CCRT-EP5+) was associated with even better 5-year FFS (62.5% versus 13.1%, p = 0.025) and CSS (75.0% versus 16.9%, p = 0.016).ConclusionsFIGO stage and lymph node metastasis are significant prognostic factors in SCNECC. In stages IIB–IVB, CCRT-EP5+ might be the treatment of choice, which could be also true for earlier stages. Despite limitations of a retrospective study spanning a long time period and heterogeneous managements, the results provide an important basis for designing future prospective studies.