The prognostic significance of tumour–stroma ratio in oestrogen receptor-positive breast cancer

Background:

A high percentage of stroma predicts poor survival in triple-negative breast cancers but is diminished in studies of unselected cases. We determined the prognostic significance of tumour–stroma ratio (TSR) in oestrogen receptor (ER)-positive male and female breast carcinomas.

Methods:

TSR was measured in haematoxylin and eosin-stained tissue sections (118 female and 62 male). Relationship of TSR (cutoff 49%) to overall survival (OS) and relapse-free survival (RFS) was analysed.

Results:

Tumours with ⩾49% stroma were associated with better survival in female (OS P=0.008, HR=0.2–0.7; RFS P=0.006, HR=0.1–0.6) and male breast cancer (OS P=0.005, HR=0.05–0.6; RFS P=0.01, HR=0.87–5.6), confirmed in multivariate analysis.

Conclusions:

High stromal content was related to better survival in ER-positive breast cancers across both genders, contrasting data in triple-negative breast cancer and highlighting the importance of considering ER status when interpreting the prognostic value of TSR.     

Effect of adjuvant trastuzumab among patients treated with anti-HER2-based neoadjuvant therapy

Purpose:

To study the impact of adjuvant trastuzumab among patients achieving a pathologic complete response (pCR) after trastuzumab-based neoadjuvant systemic therapy (NST).

Patients and methods:

Patients with primary HER2-positive breast cancer treated with trastuzumab-based NST were categorised according to adjuvant trastuzumab administration and pCR status. Adjuvant trastuzumab became standard of care in 2006, this was the main reason patients in our cohort did not receive adjuvant trastuzumab. Kaplan–Meier was used to estimate survival. A test for interaction between adjuvant trastuzumab and pCR was completed.

Findings:

Of 589 patients, 203 (34.5%) achieved a pCR. After surgery, 109 (18.5%) patients in the entire cohort did not receive adjuvant trastuzumab. Among patients achieving a pCR, 31.3% received adjuvant trastuzumab compared with 68.8% among those who did not achieve a pCR (P=0.0006). Among patients achieving pCR, adjuvant trastuzumab did not further improve overall survival (OS) or relapse-free survival (RFS) (P=0.35 and P=0.93, respectively). Any benefit of adjuvant trastuzumab in OS and RFS among patients without a pCR did not achieve statistical significance (P=0.3 and P=0.44, respectively).

Conclusions:

In this cohort, patients treated with trastuzumab-based NST who achieved a pCR have excellent outcome regardless of whether they received adjuvant trastuzumab.     

Adjuvant epirubicin followed by cyclophosphamide,methotrexate and fluorouracil (CMF) vs CMF in early breast cancer: results with over 7 years median follow-up from the randomised phase III NEAT/BR9601 trials

Background:

The National Epirubicin Adjuvant Trial (NEAT) and BR9601 trials tested the benefit of epirubicin when added to cyclophosphamide, methotrexate and 5-fluorouracil (E-CMF) compared with standard CMF in adjuvant chemotherapy for women with early breast cancer. This report details longer follow-up with interesting additional time-dependent analyses.

Methods:

National Epirubicin Adjuvant Trial used epirubicin (E) 3-weekly for four cycles followed by classical (c) CMF for four cycles (E-CMF) compared with cCMF for six cycles. BR9601 used E 3-weekly for four cycles followed by CMF 3-weekly for four cycles, compared with CMF 3-weekly for eight cycles.

Results:

In all, 2391 eligible patients were randomised and with a median 7.4-year follow-up, E-CMF confirmed a significant benefit over CMF in both relapse-free survival (RFS) (78% vs 71% 5 years RFS, respectively, hazard ratio (HR)=0.75 (95% CI: 0.65–0.86), P<0.0001) and overall survival (OS) (84% vs 78% 5 years OS, respectively, HR=0.76 (95% CI: 0.65–0.89), P=0.0007). Interaction of treatment effect and prognostic factors was demonstrated for duplication of chromosome 17 centromeric enumeration (Ch17CEP) as previously reported. Poor prognostic factors at diagnosis (ER and PR negative and HER2 positive) showed time-dependent annual hazard rates for RFS and OS. In univariate analysis, these factors demonstrated more favourable HRs for RFS after 5 years. Treatment effects also suggested a differential benefit for E-CMF within the first 5 years for poor prognosis tumours.

Conclusion:

Longer follow-up has confirmed E-CMF as significantly superior to CMF for all patients. Ch17CEP duplication was the only biomarker that demonstrated significant treatment interaction. Standard poor prognostic factors at diagnosis were time-dependent, and after 5 years disease-free, poor prognosis patients demonstrated favourable HRs for survival.     

Prognostic performance of inflammation-based prognostic indices in primary operable non-small cell lung cancer

Background:

At least 30% of patients with primary resectable non-small cell lung cancer (NSCLC) will experience a relapse in their disease within 5 years following definitive treatment. Clinicopathological predictors have proved to be suboptimal in identifying high-risk patients. We aimed to establish whether inflammation-based scores offer an improved prognostic ability in terms of estimating overall (OS) and recurrence-free survival (RFS) in a cohort of operable, early-stage NSCLC patients.

Methods:

Clinicopathological, demographic and treatment data were collected prospectively for 220 patients operated for primary NSCLC at the Hammersmith Hospital from 2004 to 2011. Pretreatment modified Glasgow Prognostic Score (mGPS), neutrophil-to-lymphocyte ratio (NLR) and platelet-to-lymphocyte ratio (PLR) were tested together with established prognostic factors in uni- and multivariate Cox regression analyses of OS and RFS.

Results:

Half of the patients were male, with a median age of 65. A total of 57% were classified as stage I with adenocarcinoma being the most prevalent subtype (60%). Univariate analyses of survival revealed stage (P<0.001), grade (P=0.02), lymphovascular (LVI, P=0.001), visceral pleural invasion (VPI, P=0.003), mGPS (P=0.02) and NLR (P=0.04) as predictors of OS, with stage (P<0.001), VPI (P=0.02) and NLR (P=0.002) being confirmed as independent prognostic factors on multivariate analyses. Patients with more advanced stage (P<0.001) and LVI (P=0.008) had significantly shorter RFS.

Conclusions:

An elevated NLR identifies operable NSCLC patients with a poor prognostic outlook and an OS difference of almost 2 years compared to those with a normal score at diagnosis. Our study validates the clinical utility of the NLR in early-stage NSCLC.     

Adjuvant chemotherapy for gastric cancer: a randomised phase 3 trial of mitomycin-C plus either short-term doxifluridine or long-term doxifluridine plus cisplatin after curative D2 gastrectomy (AMC0201)

Background:

This phase 3 study evaluated the efficacy of new adjuvant chemotherapy (MFP), which intensified the mitomycin-C (MMC) plus short-term doxifluridine (Mf) for gastric cancer.

Patients and methods:

A total of 855 patients (424 in Mf, 431 in MFP) with pathological stage II–IV (M0) gastric cancer after D2 gastrectomy were randomly assigned to receive either Mf (MMC 20 mg m⁻², followed by oral doxifluridine 460–600 mg m⁻² per day for 3 months) or MFP (MMC 20 mg m⁻², followed by oral doxifluridine 460–600 mg m⁻² per day for 12 months with 6 monthly infusions of 60 mg m⁻² of cisplatin) chemotherapy.

Results:

With a median follow-up of 6.6 years, there was no difference between the two groups in recurrence-free survival (RFS) (5-year RFS 61.1% in Mf and 57.9% in MFP; hazard ratio 1.10 (95% CI 0.89–1.35); P=0.39) and overall survival (OS) (5-year OS 66.5% in Mf and 65.0% in MFP; hazard ratio 1.11 (95% CI 0.89–1.39); P=0.33).

Conclusion:

Intensification of Mf adjuvant chemotherapy by prolonging the duration of oral fluoropyrimidine and adding cisplatin was safe but not effective to improve the survivals in curatively resected gastric cancer patients.     

Pre-treatment neutrophil-to-lymphocyte ratio as predictor of adverse outcomes in patients undergoing radical cystectomy for urothelial carcinoma of the bladder

Background:

An elevated neutrophil-to-lymphocyte ratio (NLR) is associated with poor outcome in various tumours. Its prognostic utility in patients with urothelial carcinoma of the bladder (UCB) undergoing radical cystectomy (RC) is yet to be fully elucidated.

Methods:

A cohort of patients undergoing RC for UCB in a tertiary referral centre between 1992 and 2012 was analysed. Neutrophil-to-lymphocyte ratio was computed using complete blood counts performed pre-RC, or before neo-adjuvant chemotherapy where applicable. Time-dependent receiver operating characteristic curves were used to determine the optimal cutoff point for predicting recurrence-free survival (RFS), cancer-specific survival (CSS) and overall survival (OS). The predictive ability of NLR was assessed using Kaplan–Meier analyses and multivariable Cox proportional hazards models. The likelihood-ratio test was used to determine whether multivariable models were improved by including NLR.

Results:

The cohort included 424 patients followed for a median of 58.4 months. An NLR of 3 was determined as the optimal cutoff value. Patients with an NLR⩾3.0 had significantly worse survival outcomes (5y-RFS: 53% vs 64%, log-rank P=0.013; 5y-CSS: 57% vs 75%, log-rank P<0.001; 5y-OS: 43% vs 64%, log-rank P<0.001). After adjusting for disease-specific predictors, an NLR ⩾3.0 was significantly associated with worse RFS (HR=1.49; 95% CI=1.12–2.0, P=0.007), CSS (HR=1.88; 95% CI=1.39–2.54, P<0.001) and OS (average HR=1.67; 95% CI=1.17–2.39, P=0.005). The likelihood-ratio test confirmed that prognostic models were improved by including NLR.

Conclusions:

Neutrophil-to-lymphocyte ratio is an inexpensive prognostic biomarker for patients undergoing RC for UCB. It offers pre-treatment prognostic value in addition to established prognosticators and may be helpful in guiding treatment decisions.     

The role of Cathepsin S as a marker of prognosis and predictor of chemotherapy benefit in adjuvant CRC: a pilot study

Background:

The aim of this pilot retrospective study was to investigate the immunohistochemical expression of Cathepsin S (CatS) in three cohorts of colorectal cancer (CRC) patients (n=560).

Methods:

Prevalence and association with histopathological variables were assessed across all cohorts. Association with clinical outcomes was investigated in the Northern Ireland Adjuvant Chemotherapy Trial cohort (n=211), where stage II/III CRC patients were randomised between surgery-alone or surgery with adjuvant fluorouracil/folinic acid (FU/FA) treatment.

Results:

Greater than 95% of tumours had detectable CatS expression with significantly increased staining in tumours compared with matched normal colon (P>0.001). Increasing CatS was associated with reduced recurrence-free survival (RFS; P=0.03) among patients treated with surgery alone. Adjuvant FU/FA significantly improved RFS (hazard ratio (HR), 0.33; 95% CI, 0.12–0.89) and overall survival (OS; HR, 0.25; 95% CI, 0.08–0.81) among 36 patients with high CatS. Treatment did not benefit the 66 patients with low CatS, with a RFS HR of 1.34 (95% CI, 0.60–3.19) and OS HR of 1.33 (95% CI, 0.56–3.15). Interaction between CatS and treatment status was significant for RFS (P=0.02) and OS (P=0.04) in a multivariate model adjusted for known prognostic markers.

Conclusion:

These results signify that CatS may be an important prognostic biomarker and predictive of response to adjuvant FU/FA in CRC.     

Tumour-infiltrating CD68+ and CD57+ cells predict patient outcome in stage II–III colorectal cancer

Background:

The aim of our study was to evaluate the prognostic role of immunological microenvironnement in stage II–III CRC patients.

Methods:

We constructed a tissue microarray from 196 consecutive patients with stage II–III CRC and compared CD3, CD4, CD8, CD57, CD68, CXCL9/MIG, CXCL13, and PPARγ immunoreactivity in tumour samples and their matched non-tumour tissue. We assessed their association with relapse-free survival (RFS; primary endpoint) and overall survival (OS) in multivariate Cox models.

Results:

Low densities of CD57+ and CD68+ tumour-infiltrating cells (TIC) independently predicted worse outcomes. A prognostic score combining CD57 (+, > vs −, ⩽2 cells per spot) and CD68 (+, >0 vs −, =0 cells per spot) TIC density discriminated CRC patients at low (CD68+/CD57+), intermediate (CD68+/CD57−), or high (CD68−/CD57−) risk, with hazard ratios for the intermediate-risk and high-risk groups of 2.7 (95% confidence interval (CI): 1.3–5.8) and 9.0 (3.2–25.4) for RFS, and 2.5 (1.2–5.1) and 10.6 (3.8–29.2) for OS, respectively, as compared with the low-risk group. Corresponding 5-year survival rates (95% CI) in the low-, moderate- and high-risk groups were 84% (71–91), 65% (54–74), and 12% (2–47), respectively, for RFS, and 91% (80–96), 76% (66–84), and 25% (7–59), respectively, for OS.

Conclusion:

Tumour CD57+ and CD68+ TIC density assessment independently predicts survival in patients with stage II–III CRC. If validated, our score based on a quick, inexpensive, and well-established method such as point counting on diagnostic tissue sections could be used routinely as a prognostic tool in CRC patients.     

Prognostic factors for survival in patients with metastatic renal cell carcinoma treated with targeted therapies

Background:

The most important prognostic factors for survival in patients with metastatic renal cell carcinoma (mRCC) were evaluated in the era of cytokine therapy, and only recently were revalidating in patients receiving targeted therapies (TTs).

Methods:

Clinical data for consecutive patients with mRCC who received TTs were retrieved from the database of Istituto Nazionale dei Tumori of Milan. Variables with a significant association with overall survival (OS) were estimated by proportional hazard regression, and a backward stepwise multivariate analysis identified the independent prognostic factors.

Results:

Data for 336 consecutive patients treated with TTs for RCC during the period 2004–2011 were evaluated. According to the Motzer classification, 32% patients were low risk, 48% were intermediate risk and 20% were poor risk. One hundred and sixty-seven (49.7%) patients received one TT, 116 (34.5%) received a second-line TT, 42 (12.5%) a third-line TT and 11 (3.3%) patients received a fourth-line TT. The median OS was 24 months (95% CI 20.0, 27.0) and the 5-year OS rate was 24.6% (95% CI 18.7, 30.8%). In the uni- and multivariate analysis Motzer risk classification, Fuhrman grade and previous cytokine therapy were identified as independent prognostic factors (P<0.01).

Conclusion:

The Motzer classification was confirmed as an independent prognostic factor for OS in patients with mRCC receiving TTs. Additionally, Fuhrman grade and previous cytokine therapy were independent prognostic factors for clinical outcome.     

Serum lactate dehydrogenase as an early marker for outcome in patients treated with anti-PD-1 therapy in metastatic melanoma

Background:

Treatment with programmed death receptor-1 (PD-1) antibodies is associated with high response rates in patients with advanced melanoma. Reliable markers for early response and outcome are still sparse.

Methods:

We evaluated 66 consecutive patients with advanced/metastatic melanoma treated with nivolumab or pembrolizumab between 2013 and 2014. The main objectives of this study were to investigate whether, first, serum lactate dehydrogenase (LDH) at baseline (normal vs above the upper limit of normal) correlates with overall survival (OS), and, second, whether the change of LDH during treatment predicts response before the first scan and OS in patients with an elevated baseline LDH.

Results:

After a median follow-up of 9 months, patients with an elevated baseline LDH (N=34) had a significantly shorter OS compared with patients with normal LDH (N=32; 6-month OS: 60.8% vs 81.6% and 12-month OS: 44.2% vs 71.5% (log-rank P=0.0292). In those 34 patients with elevated baseline LDH, the relative change during treatment was significantly associated with an objective response on the first scan: the 11 (32%) patients with partial remission had a mean reduction of −27.3% from elevated baseline LDH. In contrast, patients with progressive disease (N=15) had a mean increase of +39%. Patients with a relative increase over 10% from elevated baseline LDH had a significantly shorter OS compared with patients with ⩽10% change (4.3 vs 15.7 months, log-rank P<0.00623).

Conclusions:

LDH could be a useful marker at baseline and during treatment to predict early response or progression in patients with advanced melanoma who receive anti-PD-1 therapy.     

Bone marrow micrometastases in early breast cancer–30-year outcome

Background:

Micrometastases in bone marrow of women with early breast cancer were first identified immunocytochemically in the 1980s. We report on the original cohort of women with a median follow-up of 30 years.

Patients and Methods:

In total, 350 women with primary breast cancer had eight bone marrow aspirates examined with antibody to epithelial membrane antigen. Data on long-term mortality were obtained via record linkage to death certification.

Results:

At a 30-year median follow-up, 79 out of 89 (89%) patients with micrometastases have died compared with 202 out of 261 (77%) without (hazard ratio=1.46 (95% CI 1.12–1.90), P=0.0043). Most marked effect of micrometastases on overall survival (OS) was seen in patients aged ⩽50 at surgery (N=97, P=0.012), and on all patients within 10 years of diagnosis. In multivariable analyses, the presence of micrometastases was no longer a statistically significant prognostic factor.

Conclusions:

Bone marrow micrometastases are predictive for OS, particularly in the first decade and in younger patients.     

Age as an independent prognostic factor for survival of localised synovial sarcoma patients

Background:

We performed a retrospective nationwide study to explore age as a prognostic factor in synovial sarcoma patients.

Methods:

Data on 613 synovial sarcoma patients were obtained from the Netherlands Cancer Registry. The prognostic relevance of age groups (children, adolescent and young adults (AYAs), adults, and elderly) was estimated by Kaplan–Meier survival curves and multivariable Cox-proportional hazards modelling.

Results:

A total of 461 patients had localised disease at diagnosis. The 5-year overall survival (OS) was 89.3±4.6%, 73.0±3.8%, 54.7±3.6%, and 43.0±7.0% in children (n=54), AYAs (n=148), adults (n=204), and elderly (n=55), respectively. Treatment modalities had no significant effect on survival in the univariable analysis. Multivariable analysis identified age at diagnosis, tumour localisation, and tumour size as significant factors affecting OS. Both tumour localisation and size were equally distributed over the age groups.

Conclusions:

We show that outcome of synovial sarcoma patients significantly decreases with age regardless of primary tumour site, size, and treatment.     

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.     

Redefining high-risk patients with stage II colon cancer by risk index and microRNA-21: results from a population-based cohort

Background:

The aim of the present study was to analyse the prognostic value of microRNA-21 (miRNA-21) in patients with stage II colon cancer aiming at a risk index for this group of patients.

Methods:

A population-based cohort of 554 patients was included. MicroRNA-21 was analysed by qPCR based on tumour tissue. An index was created using the coefficients obtained from a collective multiple Cox regression. The entire procedure was cross-validated (10-fold). The performance of the index was quantified by time-dependent receiver operating characteristics curves.

Results:

High miRNA-21 expression was associated with an unfavourable recurrence-free cancer-specific survival (RF-CSS), hazard ratio 1.35 (95% confidence interval, 1.03–1.76) (P=0.028). The generated RF-CSS index divided the traditional high-risk patients into subgroups with 5-year RF-CSS rates of 87% and 73%, respectively (P<0.001). The overall survival (OS) index identified three different subgroups (P<0.001). Cross-validated 5-year OS rates were 88%, 68%, and 50%, respectively.

Conclusions:

This population-based study supports miRNA-21 as an additional prognostic biomarker in patients with stage II colon cancer. Furthermore, the introduction of a risk index may guide the use of postoperative adjuvant treatment in a more appropriate way compared with current practice.     

Randomised phase II study comparing dose-escalated weekly paclitaxel vs standard-dose weekly paclitaxel for patients with previously treated advanced gastric cancer

Background:

This randomised phase II trial compared dose-escalated weekly paclitaxel (wPTX) vs standard-dose wPTX for patients with previously treated advanced gastric cancer (AGC).

Methods:

Ninety patients were randomised to a standard dose of wPTX (80 mg m⁻²) or an escalated dose of wPTX (80–120 mg m⁻²) to assess the superiority of overall survival (OS) with a one-sided alpha error of 0.3 and a power of 0.8.

Results:

The median OS showed a trend towards longer survival in the dose-escalated arm (11.8 vs 9.6 months; hazard ratio (HR), 0.75; one-sided P=0.12), although it was statistically not significant. The median progression-free survival (PFS) was significantly longer in the dose-escalated arm (4.3 vs 2.5 months, HR, 0.55; P=0.017). Objective response rate was 30.3% with dose escalation and 17.1% with standard dose (P=0.2). The frequency of all grades of neutropenia was significantly higher with dose escalation (88.7% vs 60.0%, P=0.002); however, no significant difference was observed in the proportion of patients experiencing grade 3 or more (40.9% vs 31.1%, P=0.34).

Conclusion:

Dose-escalated wPTX in patients with pretreated AGC met our predefined threshold of primary end point, OS (P<0.3); however, it did not show a significantly longer OS. Progression-free survival was significantly better with dose escalation.     

KRAS and BRAF mutations are prognostic biomarkers in patients undergoing lung metastasectomy of colorectal cancer

Background:

We evaluated KRAS (mKRAS (mutant KRAS)) and BRAF (mBRAF (mutant BRAF)) mutations to determine their prognostic potential in assessing patients with colorectal cancer (CRC) for lung metastasectomy.

Methods:

Data were reviewed from 180 patients with a diagnosis of CRC who underwent a lung metastasectomy between January 1998 and December 2011.

Results:

Molecular analysis revealed mKRAS in 93 patients (51.7%), mBRAF in 19 patients (10.6%). In univariate analyses, overall survival (OS) was influenced by thoracic nodal status (median OS: 98 months for pN−, 27 months for pN+, P<0.0001), multiple thoracic metastases (75 months vs 101 months, P=0.008) or a history of liver metastases (94 months vs 101 months, P=0.04). mBRAF had a significantly worse OS than mKRAS and wild type (WT) (P<0.0001). The 5-year OS was 0% for mBRAF, 44% for mKRAS and 100% for WT, with corresponding median OS of 15, 55 and 98 months, respectively (P<0.0001). In multivariate analysis, WT BRAF (HR: 0.005 (95% CI: 0.001–0.02), P<0.0001) and WT KRAS (HR: 0.04 (95% CI: 0.02–0.1), P<0.0001) had a significant impact on OS.

Conclusions:

mKRAS and mBRAF seem to be prognostic factors in patients with CRC who undergo lung metastasectomy. Further studies are necessary.     

Tumour shrinkage measured with first treatment evaluation under VEGF-targeted therapy as prognostic marker in metastatic renal cell carcinoma (mRCC)

Background:

The aim of our analysis is to further characterise the prognostic relevance of early tumour shrinkage (TS) during VEGF-targeted therapy in mRCC, in order to explore whether this could define a group of patients with long-term survivorship.

Methods:

A hundred patients were stratified into five subgroups according to their change of tumour size with first treatment evaluation: −100% to −60% −59% to −30% and −29% to 0% TS or gain of tumour size from 1% to 19% and ⩾20% or occurrence of new lesions (i.e., progressive disease).

Results:

The median PFS and OS were 10.4 months and 28.2 months, respectively. The median OS stratified according to the subgroups as described above was 77.4, 33.5, 26.9, 30.0 and 14.3 months, respectively. Multivariate analysis revealed early TS as a prognostic marker (P=0.021; HR 1.624).

Conclusion:

The extent of TS defines a small proportion of patients with an excellent prognosis. Larger studies are warranted to define the relationship of long-term survivorship and extent of TS with targeted therapies.     

Multivariate prognostic factors analysis for second-line chemotherapy in advanced biliary tract cancer

Background:

The role of second-line chemotherapy (CT) is not established in advanced biliary tract cancer (aBTC). We investigated the outcome of aBTC patients treated with second-line CT and devised a prognostic model.

Methods:

Baseline clinical and laboratory data of 300 consecutive aBTC patients were collected and association with overall survival (OS) was investigated by multivariable Cox models.

Results:

The following parameters resulted independently associated with longer OS: Eastern Cooperative Oncology Group performance status of 0 (P<0.001; hazard ratio (HR), 0.348; 95% confidence interval (CI) 0.215–0.562), CA19.9 lower than median (P=0.013; HR, 0.574; 95% CI 0.370–0.891), progression-free survival after first-line CT ⩾6 months (P=0.027; HR, 0.633; 95% CI 0.422–0.949) and previous surgery on primary tumour (P=0.027; HR, 0.609; 95% CI 0.392–0.945). We grouped the 249 patients with complete data available into three categories according to the number of fulfilled risk factors: median OS times for good-risk (zero to one factors), intermediate-risk (two factors) and poor-risk (three to four factors) groups were 13.1, 6.6 and 3.7 months, respectively (P<0.001).

Conclusions:

Easily available clinical and laboratory factors predict prognosis of aBTC patients undergoing second-line CT. This model allows individual patient-risk stratification and may help in treatment decision and trial design.     

The prognostic value of CDKN2A hypermethylation in colorectal cancer: a meta-analysis

Background:

The prognostic value of CDKN2A promoter hypermethylation in colorectal cancer remains controversial. We systematically reviewed the evidence for assessment of CDKN2A methylation in colorectal cancer to elucidate this issue.

Methods:

Pubmed, Embase and ISI web of knowledge were searched to identify eligible studies to evaluate the association of CDKN2A hypermethylation and overall survival and clinicopathological features of colorectal cancer patients. Combined hazard ratios (HRs) or odds ratios (ORs) with 95% confidence interval (95% CI) were pooled using a random-effects model.

Results:

A total of 11 studies encompassing 3440 patients were included in the meta-analysis. CDKN2A hypermethylation had an unfavourable impact on OS of patients with colorectal cancer (HR 1.65, 95% CI 1.29–2.11). Subgroup analysis indicated that CDKN2A hypermethylation was significantly correlated with OS in Europe (HR 1.49; 95% CI 1.28–1.74) and Asia (HR 3.30; 95% CI 1.68–6.46). Furthermore, there was a significant association between CDKN2A hypermethylation and lymphovascular invasion (OR 1.68, 95% CI 1.15–2.47), lymph node metastasis (OR 1.68, 95% CI 1.09–2.59) and proximal tumour location (OR 2.09, 95% CI 1.34–3.26) of colorectal cancer.

Conclusion:

This meta-analysis indicated that CDKN2A hypermethylation might be a predictive factor for unfavourable prognosis of colorectal cancer patients.     

Impact of mutational status on survival in low-grade serous carcinoma of the ovary or peritoneum

Background:

Low-grade serous carcinoma of the ovary or peritoneum is a distinct, well- recognized histologic subtype characterized by young age at diagnosis, relative chemoresistance, and prolonged overall survival. Common mutations reported to be found within this subtype include KRAS and BRAF.

Methods:

Using clinical information of patients from our IRB-approved registry and tissue from a subset of these patients, we performed mutational analysis for KRAS and BRAF using the direct Sanger sequencing technique and correlated findings with the clinical outcome, overall survival (OS).

Results:

In 79 cases, patients with KRAS or BRAF mutations (n=21) had a significantly better OS than those with wild-type KRAS or BRAF (n=58) (106.7 months (95% CI, 50.6, 162.9) vs 66.8 months (95% CI, 43.6, 90.0)), respectively (P=0.018).

Conclusions:

Mutational status appears to be a potential prognostic factor in low-grade serous carcinoma of the ovary or peritoneum.