A molecular signature for the prediction of recurrence in colorectal cancer

Background

Several clinical and pathological factors have an impact on the prognosis of colorectal cancer (CRC), but they are not yet adequate for risk assessment. We aimed to identify a molecular signature that can reliably identify CRC patients at high risk for recurrence.

Results

Two hundred eighty-one CRC samples (stage II/III) were included in this study. A two-step gene expression profiling study was conducted. First, gene expression measurements from 81 fresh frozen CRC samples were obtained using Affymetrix Human Genome U133 Plus 2.0 Arrays. Second, a focused gene expression assay, including prognostic genes and genes of interest from literature reviews, was performed using 200 fresh frozen samples and a Taqman low-density array (TLDA) analysis. An optimal 31-gene expression classifier for the prediction of recurrence among patients with stage II/III CRC was developed using logistic regression analysis. This gene expression signature classified 58.5% of patients as low-risk and 41.5% as high-risk (P < 0.001). The signature was the strongest independent prognostic factor in the multivariate analysis. The five-year relapse-free survival (RFS) rates for the low-risk patients and the high-risk patients were 88.5% and 41.3% (P < 0.001), respectively.

Conclusion

We identified a 31-gene expression signature that is closely associated with the clinical outcome of stage II/III CRC patients.     

Elevated kinesin family member 26B is a prognostic biomarker and a potential therapeutic target for colorectal cancer

Background

Kinesins play a key role in the development and progression of many human cancers. The present study investigated the expression and clinical significance of kinesin family member 26B (KIF26B) in colorectal cancer (CRC).

Methods

Using quantitative real-time PCR and Western blot analyses as well as immunohistochemical staining of a tissue microarray we examined KIF26B mRNA and protein levels in CRC tumor tissues and paired adjacent normal mucosa. Moreover, the effect of KIF26B knockdown on CRC cell proliferation was investigated using Cell Counting Kit-8 assays.

Results

Expression of KIF26B was found to be elevated in CRC. Suppression of KIF26B inhibited CRC cell proliferation. Furthermore, upregulated expression of KIF26B was significantly correlated with tumor size (P = 0.020), American Joint Committee on Cancer (AJCC) stage (P = 0.018), T stage (P = 0.026), N stage (P = 0.013), and differentiation histology (P = 0.047). KIF26B was also shown to be an independent prognostic indicator of overall survival for CRC patients (HR 5.621; 95% CI 2.302–13.730; P < 0.001).

Conclusion

Our data indicate that KIF26B plays an important role in colorectal carcinogenesis and functions as a novel prognostic indicator and a potential therapeutic target for CRC.     

Prognostic impact of family history in southern Chinese patients with undifferentiated nasopharyngeal carcinoma

Background:

Family history of cancer is associated with developing nasopharyngeal carcinoma (NPC); however, the impact of it on survival among established NPC patients remains unknown.

Methods:

We retrospectively analysed 1773 southern Chinese patients. Associations between a first-degree family history of NPC and overall survival (OS), locoregional relapse-free survival (LRFS) and distant metastasis-free survival (DMFS) were estimated by Cox regression.

Results:

Among 1773 patients, 207 (11.7%) reported a first-degree family history of NPC. Compared with patients without a family history, the adjusted hazard ratios among those with it were 0.60 (95% confidence interval (CI), 0.37–0.98; P=0.040) for OS, 0.52 (95% CI, 0.24–1.12; P=0.096) for LRFS and 0.51 (95% CI, 0.27–0.97; P=0.040) for DMFS. There were trends for improving OS, LRFS and DMFS with increasing number of affected relatives (P_trend: 0.050, 0.114 and 0.044, respectively). But no significant benefits of family history in second- or third-degree relatives were observed. In subgroup analysis, we observed the effects of family history with restriction to male patients and those of advanced stage and treated with conventional radiotherapy and addition of chemotherapy.

Conclusion:

A first-degree family history of NPC is associated with improved survival of patients.     

Identification of a low-risk subgroup of HER-2-positive breast cancer by the 70-gene prognosis signature

Background:

Overexpression of HER-2 is observed in 15–25% of breast cancers, and is associated with increased risk of recurrence. Current guidelines recommend trastuzumab and chemotherapy for most HER-2-positive patients. However, the majority of patients does not recur and might thus be overtreated with adjuvant systemic therapy. We investigated whether the 70-gene MammaPrint signature identifies HER-2-positive patients with favourable outcome.

Methods:

In all, 168 T1–3, N0–1, HER-2-positive patients were identified from a pooled database, classified by the 70-gene signature as good or poor prognosis, and correlated with long-term outcome. A total of 89 of these patients did not receive adjuvant chemotherapy.

Results:

In the group of 89 chemotherapy-naive patients, after a median follow-up of 7.4 years, 35 (39%) distant recurrences and 29 (33%) breast cancer-specific deaths occurred. The 70-gene signature classified 20 (22%) patients as good prognosis, with 10-year distant disease-free survival (DDFS) of 84%, compared with 69 (78%) poor prognosis patients with 10-year DDFS of 55%. The estimated hazard ratios (HRs) were 4.5 (95% confidence interval (CI) 1.1–18.7, P=0.04) and 3.8 (95% CI 0.9–15.8, P=0.07) for DDFS and breast cancer-specific survival (BCSS), respectively. In multivariate analysis adjusted for known prognostic factors and hormonal therapy, HRs were 5.8 (95% CI 1.3–26.7, P=0.03) and 4.7 (95% CI 1.0–21.7, P=0.05) for DDFS and BCSS, respectively.

Interpretation:

The 70-gene prognosis signature is an independent prognostic indicator that identifies a subgroup of HER-2-positive early breast cancer with a favourable long-term outcome.     

A panel of eight-miRNA signature as a potential biomarker for predicting survival in bladder cancer

Background

There is increasing evidence to suggest that miRNAs play an important role in predicting cancer survival. To identify a panel of miRNA signature that can divided tumor from normal bladder using miRNA expression levels, and to assess the prognostic value of this specific miRNA markers in bladder cancer (BCa).

Methods

A comprehensive meta-review of published miRNA expression profiles that compared BCa and adjacent normal tissues was performed to determine candidate miRNAs as prognostic biomarkers for BCa. Vote-counting strategy and Robust Rank Aggregation method were used to identify significant meta-signature miRNAs.

Results

We identified an eight-miRNA signature including three upregulated (miR-141, miR-200c, miR-21) and five downregulated (miR-145, miR-125, miR-199a, let-7c and miR-99a) miRNAs for the prediction of overall survival (OS) using TCGA dataset, and validated in our 48 BCa patients. X-tile plot was used to generate the optimum cut-off point and Kaplan-Meier method was used to calculate OS. A linear prognostic model of eight miRNAs was constructed and weighted by the importance scores from the supervised principal component method to divide patients into high- and low-risk groups. Patients assigned to the high-risk group were associated with poor OS compared with patients in the low-risk group (HR = 5.21, p < 0.001). Our validation cohort of 48 patients confirmed the panel of 8-miRNAs as a reliable prognostic tool for OS in patients with BCa (HR = 5.04, p < 0.001).

Conclusion

The present meta-analysis identified eight highly significant and consistently dysregulated miRNAs from 19 datasets. We also constructed an eight-miRNA signature which provided predictive and prognostic value that complements traditional clinicopathological risk factors.

Electronic supplementary material

The online version of this article (doi:10.1186/s13046-015-0167-0) contains supplementary material, which is available to authorized users.     

Circulating prolactin and in situ breast cancer risk in the European EPIC cohort: a case-control study

Introduction

The relationship between circulating prolactin and invasive breast cancer has been investigated previously, but the association between prolactin levels and in situ breast cancer risk has received less attention.

Methods

We analysed the relationship between pre-diagnostic prolactin levels and the risk of in situ breast cancer overall, and by menopausal status and use of postmenopausal hormone therapy (HT) at blood donation. Conditional logistic regression was used to assess this association in a case-control study nested within the European Prospective Investigation into Cancer and Nutrition (EPIC) cohort, including 307 in situ breast cancer cases and their matched control subjects.

Results

We found a significant positive association between higher circulating prolactin levels and risk of in situ breast cancer among all women [pre-and postmenopausal combined, OR_log2 = 1.35 (95% CI 1.04-1.76), P_trend = 0.03]. No statistically significant heterogeneity was found between prolactin levels and in situ cancer risk by menopausal status (P_het = 0.98) or baseline HT use (P_het = 0.20), although the observed association was more pronounced among postmenopausal women using HT compared to non-users (P_trend = 0.06 vs P_trend = 0.35). In subgroup analyses, the observed positive association was strongest in women diagnosed with in situ breast tumors <4 years compared to ≥4 years after blood donation (P_trend = 0.01 vs P_trend = 0.63; P_het = 0.04) and among nulliparous women compared to parous women (P_trend = 0.03 vs P_trend = 0.15; P_het = 0.07).

Conclusions

Our data extends prior research linking prolactin and invasive breast cancer to the outcome of in situ breast tumours and shows that higher circulating prolactin is associated with increased risk of in situ breast cancer.     

Obesity and survival in operable breast cancer patients treated with adjuvant anthracyclines and taxanes according to pathological subtypes: a pooled analysis

Introduction

Obesity is an unfavorable prognostic factor in breast cancer (BC) patients regardless of menopausal status and treatment received. However, the association between obesity and survival outcome by pathological subtype requires further clarification.

Methods

We performed a retrospective analysis including 5,683 operable BC patients enrolled in four randomized clinical trials (GEICAM/9906, GEICAM/9805, GEICAM/2003–02, and BCIRG 001) evaluating anthracyclines and taxanes as adjuvant treatments. Our primary aim was to assess the prognostic effect of body mass index (BMI) on disease recurrence, breast cancer mortality (BCM), and overall mortality (OM). A secondary aim was to detect differences of such prognostic effects by subtype.

Results

Multivariate survival analyses adjusting for age, tumor size, nodal status, menopausal status, surgery type, histological grade, hormone receptor status, human epidermal growth factor receptor 2 (HER2) status, chemotherapy regimen, and under-treatment showed that obese patients (BMI 30.0 to 34.9) had similar prognoses to that of patients with a BMI < 25 (reference group) in terms of recurrence (Hazard Ratio [HR] = 1.08, 95% Confidence Interval [CI] = 0.90 to 1.30), BCM (HR = 1.02, 0.81 to 1.29), and OM (HR = 0.97, 0.78 to 1.19). Patients with severe obesity (BMI ≥ 35) had a significantly increased risk of recurrence (HR = 1.26, 1.00 to 1.59, P = 0.048), BCM (HR = 1.32, 1.00 to 1.74, P = 0.050), and OM (HR = 1.35, 1.06 to 1.71, P = 0.016) compared to our reference group. The prognostic effect of severe obesity did not vary by subtype.

Conclusions

Severely obese patients treated with anthracyclines and taxanes present a worse prognosis regarding recurrence, BCM, and OM than patients with BMI < 25. The magnitude of the harmful effect of BMI on survival-related outcomes was similar across subtypes.     

Sarcopenia and body mass index predict sunitinib-induced early dose-limiting toxicities in renal cancer patients

Background:

Little is known on factors predicting sunitinib toxicity. Recently, the condition of low muscle mass, named sarcopenia, was identified as a significant predictor of toxicity in metastatic renal cell cancer (mRCC) patients treated with sorafenib. We investigated whether sarcopenia could predict early dose-limiting toxicities (DLTs) occurrence in mRCC patients treated with sunitinib.

Methods:

Consecutive mRCC patients treated with sunitinib were retrospectively reviewed. A DLT was defined as any toxicity leading to dose reduction or treatment discontinuation. Body composition was evaluated using CT scan obtained within 1 month before treatment initiation.

Results:

Among 61 patients eligible for analysis, 52.5% were sarcopenic and 32.8% had both sarcopenia and a body mass index (BMI)<25 kg m⁻². Eighteen patients (29.5%) experienced a DLT during the first cycle. Sarcopenic patients with a BMI<25 kg m⁻² experienced more DLTs (P=0.01; odds ratio=4.1; 95% CI: (1.3–13.3)), more cumulative grade 2 or 3 toxicities (P=0.008), more grade 3 toxicities (P=0.04) and more acute vascular toxicities (P=0.009).

Conclusion:

Patients with sarcopenia and a BMI<25 kg m⁻² experienced significantly more DLTs during the first cycle of treatment.     

FOXP3 gene polymorphism is associated with hepatitis B-related hepatocellular carcinoma in China

Background

Previous evidence has shown that the FOXP3 gene was involved in the pathogenesis of several tumors; however, the correlation between single nucleotide polymorphisms (SNPs) in the FOXP3 gene and the susceptibility to hepatitis B-related hepatocellular carcinoma (HCC) remains unclear.

Methods

We analyzed two SNPs in the FOXP3 gene, rs2280883 and rs3761549, in 392 patients with HCC, 344 patients with chronic hepatitis B (CHB) and 372 matched healthy controls. Genotyping was performed by MALDI-TOF Mass Spectrometry for all donors.

Results

Compared to healthy controls, HCC patients had higher frequencies of the TT genotype (79.6%) at rs2280883 and the CC genotype (77.6%) at rs3761549 of the FOXP3 gene; CHB patients also had higher frequencies of the TT genotype (74.1%) at rs2280883 and the CC genotype (74.6%) at rs3761549. There were no significant differences in the distribution of FOXP3 genotypes between CHB donors and HCC donors. The TT genotype at rs2280883 was more frequent in patients with HCC than healthy donors (P = 0.01), but no significant difference was observed in this genotype between CHB and healthy donors (P = 0.479). C allele frequency at rs3761549 was higher in HCC patients than healthy donors (P = 0.03), but distribution of this allele was not significantly different between CHB patients and healthy donors (P = 0.11). Stratified analysis showed that the CC genotype at rs3761549 was significantly associated with a high incidence of portal vein tumor thrombus (P = 0.02) and that the TT/CT genotype at rs3761549 was significantly associated with an increased rate of tumor recurrence in HCC patients (P = 0.001).

Conclusions

Our results suggested that the FOXP3 gene polymorphisms at rs2280883 and rs3761549 may be associated with hepatitis B-related HCC. At rs3761549, the CC genotype and the TT/CT genotype were associated with a high incidence of portal vein tumor thrombus and tumor recurrence, respectively.     

Developmental pluripotency-associated 4: a novel predictor for prognosis and a potential therapeutic target for colon cancer

Backgrounds

Developmental pluripotency-associated 4 (Dppa4) gene plays an important role in self-renewal and pluripotency sustainability in embryonic stem cells. It is re-expressed in several malignant tumors and is identified as a new pluripotency-related oncogene. The present study investigates the expression and clinical significance of Dppa4 in colon cancer.

Methods

Real-time polymerase chain reaction and Western blotting were used to evaluate Dppa4 mRNA and protein expression in 39 pairs of fresh-frozzen colon cancer samples, which were compared with adjacent normal mucosa. The Dppa4 protein was evaluated by immunohistochemical techniques using colon tissue microarrays (TMA). The sample included 185 cancer specimens and corresponding normal colorectal mucosa. The effect of Dppa4 knockdown on colorectal cancer cell proliferation was investigated using Cell Counting Kit-8 (CCK8) assays and colony-formation assays.

Results

Both the mRNA and protein level expression of Dppa4 gene was found to be upregulated in colon cancer tissues. Furthermore, the upregulated expression of Dppa4 was significantly correlated with the results of American Joint Committee on Cancer (AJCC) stage (P = 0.01), invasion depth (P = 0.028), nodal involvement (P = 0.012), distant metastasis (P = 0.003), and differentiation (P = 0.002). Dppa4 was also shown to be an independent prognostic indicator of disease-free survival (HR 6.118, 95 % CI 3.004–12.462) and overall survival (HR 6.348, 95 % CI 2.875–14.014) for patients with colon cancer. Knockdown of Dppa4 expression inhibited the proliferation of colorectal cancer cell lines through G1/S transition regulation.

Conclusion

The results indicate that Dppa4 might play an important role in colon cancer progression and function as a novel prognostic indicator and a potential therapeutic target.     

Identification of neutrophil-derived proteases and angiotensin II as biomarkers of cancer cachexia

Background:

Cachexia is a metabolic disorder characterised by muscle wasting, diminished response to anti-cancer treatments and poor quality of life. Our objective was to identify blood-based biomarkers of cachexia in advanced cancer patients. Hence, we characterised the plasma cytokine and blood cell mRNA profiles of patients grouped in three cohorts: patients with cachexia, pre-cachexia (no cachexia but high CRP levels: ⩾5 mg l⁻¹) and no cachexia (no cachexia and CRP: <5 mg l⁻¹).

Methods:

A total of 122 newly diagnosed cancer patients with seven cancer types were studied prior to their initial therapy. Plasma levels of 22 cytokines were quantified using the bio-plex technology. mRNAs isolated from whole blood and expression profiles were determined by the chip array technology and Ingenuity Pathway Analysis (IPA) software.

Results:

In comparison with non-cachectic individuals, both pre-cachectic and cachectic patients showed an increase (⩾1.5-folds) in mRNA expression of neutrophil-derived proteases (NDPs) and significantly elevated angiotensin II (Ang II) (P=0.005 and P=0.02, respectively), TGFβ1 (P=0.042 and P<0.0001, respectively) and CRP (both P<0.0001) in the plasma. Moreover, cachectic patients displayed a significant increase in IL-6 (P=0.005), IL-8 (P=0.001) and absolute neutrophil counts (P=0.007).

Conclusions:

Ang II, TGFβ1, CRP and NDP are blood biomarkers for cancer cachexia. These findings contribute to early diagnosis and prevention of cachexia.     

Secondary cytoreduction surgery improves prognosis in platinum-sensitive recurrent ovarian cancer

Background

There is no consensus regarding the secondary cytoreduction surgery (CRS) in recurrent ovarian cancer patients. The present study aims to determine the value of secondary CRS and the eligible subgroup for this procedure.

Methods

96 platinum-sensitive recurrent ovarian cancer patients were recruited from Jiangsu Institute of Cancer Research between 1992 and 2011. Follow-up was conducted based on the surveillance protocol of MD Anderson Cancer Center. Cox proportional hazards model and log-rank test were used to assess the associations between the survival durations and covariates. Logistic regression analysis was used to explore optimal secondary CRS related factors.

Results

Optimal secondary CRS was associated with time to progression (TTP) and overall survival (OS) in patients (p < 0.01 both). Optimal secondary CRS and asymptomatic recurrent were similarly associated with longer OS (median: 79.2 vs. 53.9 and 76.1 vs. 56.0 months with p = 0.02 and p = 0.04, respectively) and TTP (median: 13.9 vs. 10.5 and 19.3 vs. 9.0 months with p = 0.02 and p = 0.03, respectively) than counterparts. Optimal initial CRS (p = 0.01), asymptomatic recurrent (p = 0.02) and longer progression-free survival duration (p = 0.02) were the independent indicators of optimal secondary CRS.

Conclusions

Optimal secondary CRS had survival benefit for platinum-sensitive epithelial ovarian cancer. Asymptomatic recurrent was one of the recruited factors for this procedure.     

Mismatch repair status in patients with primary operable colorectal cancer: associations with the local and systemic tumour environment

Background:

Mismatch repair-deficient (dMMR) colorectal cancer (CRC) is associated with a conspicuous local immune infiltrate; however, its relationship with systemic inflammatory responses remains to be determined. The present study aims to examine the relationships and prognostic value of assessment of the local and systemic environment in the context of MMR status in patients with CRC.

Methods:

The relationship between MMR status, determined using immunohistochemistry, and the local inflammatory cell infiltrate, differential white cell count, neutrophil : platelet score (NPS), neutrophil : lymphocyte ratio and modified Glasgow Prognostic Score (mGPS), and cancer-specific survival was examined in 228 patients undergoing resection of stage I–III CRC.

Results:

Thirty-five patients (15%) had dMMR CRC. Mismatch repair deficiency was associated with a higher density of CD3⁺, CD8⁺ and CD45R0⁺ T lymphocytes within the cancer cell nests and an elevated mGPS (mGPS2: 23% vs 9%, P=0.007) and NPS (NPS2: 19% vs 3%, P=0.001). CD3⁺ density (P<0.001), mGPS (P=0.01) and NPS (P=0.042) were associated with survival independent of MMR status (P=0.367) and stratified 5-year survival of patients with MMR-competent CRC from 94% to 67%, 83% to 46% and 78% to 60% respectively.

Conclusions:

Mismatch repair deficiency was associated with local and systemic environments, and in comparison with their assessment, dMMR had relatively poor prognostic value in patients with primary operable CRC. In addition to MMR status, local and systemic inflammatory responses should be assessed in these patients.     

Optimizing CIGB-300 intralesional delivery in locally advanced cervical cancer

Background:

We conducted a phase 1 trial in patients with locally advanced cervical cancer by injecting 0.5 ml of the CK2-antagonist CIGB-300 in two different sites on tumours to assess tumour uptake, safety, pharmacodynamic activity and identify the recommended dose.

Methods:

Fourteen patients were treated with intralesional injections containing 35 or 70 mg of CIGB-300 in three alternate cycles of three consecutive days each before standard chemoradiotherapy. Tumour uptake was determined using ⁹⁹Tc-radiolabelled peptide. In situ B23/nucleophosmin was determined by immunohistochemistry.

Results:

Maximum tumour uptake for CIGB-300 70-mg dose was significantly higher than the one observed for 35 mg: 16.1±8.9 vs 31.3±12.9 mg (P=0.01). Both, AUC_24h and biological half-life were also significantly higher using 70 mg of CIGB-300 (P<0.001). Unincorporated CIGB-300 diffused rapidly to blood and was mainly distributed towards kidneys, and marginally in liver, lungs, heart and spleen. There was no DLT and moderate allergic-like reactions were the most common systemic side effect with strong correlation between unincorporated CIGB-300 and histamine levels in blood. CIGB-300, 70 mg, downregulated B23/nucleophosmin (P=0.03) in tumour specimens.

Conclusion:

Intralesional injections of 70 mg CIGB-300 in two sites (0.5 ml per injection) and this treatment plan are recommended to be evaluated in phase 2 studies.     

Circulating tumor cells in newly diagnosed inflammatory breast cancer

Introduction

Circulating tumor cells (CTCs) are an independent prognostic factor for progression-free survival (PFS) and overall survival (OS) in patients with metastatic breast cancer. Inflammatory breast cancer (IBC) is one of the most aggressive forms of breast cancer. The prognostic value of a CTC count in newly diagnosed IBC has not been established. The aim of this study was to assess the prognostic value of a baseline CTC count in patients with newly diagnosed IBC.

Methods

This retrospective study included 147 patients with newly diagnosed IBC (77 with locally advanced and 70 with metastatic IBC) treated with neoadjuvant therapy or first-line chemotherapy during the period from January 2004 through December 2012 at The University of Texas MD Anderson Cancer Center. CTCs were detected and enumerated by using the CellSearch system before patients were started with chemotherapy.

Results

The proportion of patients with ≥1 CTC was lower among patients with stage III than among patients with metastatic IBC (54.5% versus 84.3%; P = 0.0002); the proportion of patients with ≥5 CTCs was also lower for stage III than for metastatic IBC (19.5% versus 47.1%; P = 0.0004). Patients with fewer than five CTCs had significantly better progression-free survival (PFS) (hazard ratio (HR) = 0.60; P = 0.02) and overall survival (HR = 0.59; P = 0.03) than patients with five or more CTCs. Among patients with stage III IBC, there was a nonsignificant difference in PFS (HR = 0.66; 95% confidence interval (CI), 0.31 to 1.39; P = 0.29) and OS (HR = 0.54; 95% CI, 0.24 to 1.26; P = 0.48) in patients with no CTCs compared with patients with one or more CTCs. In multivariate analysis, CTC was prognostic for PFS and OS independent of clinical stage.

Conclusions

CTCs can be detected in a large proportion of patients with newly diagnosed IBC and are a strong predictor of worse prognosis in patients with newly diagnosed IBC.     

The risk of cancer in primary care patients with hypercalcaemia: a cohort study using electronic records

Background:

The risk of cancer with hypercalcaemia in primary care is unknown.

Methods:

This was a cohort study using calcium results in patients aged ⩾40 years in a primary care electronic data set. Diagnoses of cancer in the following year were identified.

Results:

Participants (54 267) had calcium results: 1674 (3%) were ⩾2.6 mmol l⁻¹. Hypercalcaemia was strongly associated with cancer, especially in males: OR 2.92, 95% CI 2.17–3.93, P=<0.001; positive predictive value (PPV) 11.5% females: OR 1.86, 95% CI 1.39–2.50, P<0.001: PPV 4.1%.

Conclusions:

Hypercalcaemia is strongly associated with cancer in primary care, with men at most risk, despite hypercalcaemia being more common in women.     

The significant survival advantage of female sex in nasopharyngeal carcinoma: a propensity-matched analysis

Background:

Whether females have better survival than males in nasopharyngeal carcinoma is barely acknowledged and the exact explanations remain unknown.

Methods:

Overall, 5929 patients receiving treatment between January 2005 and December 2010 were separately stratified by stage into early and advanced stage groups, and by age into premenopausal (⩽45 years), menopausal (46–54 years) and postmenopausal (⩾55 years) groups. Matched males and females in each group were identified using the propensity score matching method. Differences in disease-free survival (DSS), overall survival (OS), distant metastasis-free survival (DMFS) and locoregional relapse-free survival (LRFS) were estimated by the Kaplan–Meier method and Cox regression model.

Results:

Overall, 398, 923, 744, 319 and 313 pairs of males and females were matched in early stage, advanced stage, premenopausal, menopausal and postmenopausal group, respectively. Females showed significant advantage over males across all end points in both early and advanced stage groups (P⩽0.042). However, this advantage persisted at premenopausal age (P⩽0.042), declined during menopause (DMFS, P=0.021; DSS, P=0.100; OS, P=0.693; LRFS, P=0.330) and totally disappeared at postmenopausal age (P⩾0.344).

Conclusions:

Sex significantly affects NPC survival, with a definite female advantage regardless of tumour stage. Intrinsic biologic traits appear to be the exact explanation according to the declining magnitude of sex effect with age.     

A randomised phase II/III trial of 3-weekly cisplatin-based sequential transarterial chemoembolisation vs embolisation alone for hepatocellular carcinoma

Background:

Transarterial chemoembolisation (TACE) has not been shown to be superior to bland embolisation (TAE) for treatment of hepatocellular carcinoma (HCC).

Methods:

We conducted a randomised phase II/III trial in patients with untreated HCC. Patients were randomised to TAE with polyvinyl alcohol (PVA) particles alone or sequential TACE (sTACE) in which cisplatin 50 mg was administered intrarterially 4–6 h before PVA embolisation. Treatment was repeated 3-weekly for up to three treatments. The primary endpoint was overall survival and secondary endpoints were progression-free survival, toxicity and response. Target sample sizes for phase II and III were 80 and 322.

Results:

The trial was terminated at phase II after 86 patients had been randomised. Patients were well matched for prognostic criteria. All three planned treatments were given to 57.1% (TAE) and 56.8% (TACE) patients. Grade 3/4 toxicity occurred in 63.5% and 83.7%, respectively (P=0.019). End-of-treatment RECIST response (CR+PR) was 13.2 and 32.6% (P=0.04) (mRECIST 47.3% and 67.4) and median overall survival and progression-free survival was 17.3 vs 16.3 (P=0.74) months and 7.2 vs 7.5 (P=0.59), respectively.

Conclusion:

Transarterial chemoembolisation according this novel schedule is feasible and associated with a higher response rate than TAE alone. The survival benefit of TACE over TAE remains unproven.     

Serum apolipoprotein A-I is a novel prognostic indicator for non-metastatic nasopharyngeal carcinoma

Background

We investigated the value of pretreatment serum apolipoprotein A-I (ApoA-I) in complementing TNM staging in the prognosis of non-metastatic nasopharyngeal carcinoma (NPC).

Patients and methods

We retrospectively reviewed 1196 newly diagnosed patients with non-metastatic NPC. Disease-specific survival (DSS), distant metastasis-free survival (DMFS), and locoregional recurrence-free survival (LRFS) rates were compared according to serum ApoA-I level. Multivariate analysis was performed to assess the prognostic value of serum ApoA-I.

Results

The 5-year DSS, DMFS, and LRFS rates for patients with elevated or decreased serum ApoA-I were 81.3% versus 69.3% (P < 0.001), 83.4% versus 67.4% (P < 0.001), and 80.9% versus 67.3% (P < 0.001), respectively. ApoA-I ≥ 1.025 g/L was an independent prognostic factor for superior DSS, DMFS, and LRFS in multivariate analysis. After stratification by clinical stage, serum ApoA-I remained a clinically and statistically significant predictor of prognosis.

Conclusion

Our data suggest that the level of ApoA-I at diagnosis is a novel independent prognostic marker that could complement clinical staging for risk definition in non-metastatic NPC.