Prognostic significance of circumferential resection margin involvement following oesophagectomy for cancer and the predictive role of endoluminal ultrasonography

Background:

The optimum multimodal treatment for oesophageal cancer, and the prognostic significance of histopathological tumour involvement of the circumferential resection margin (CRM+) are uncertain. The aims of this study were to determine the prognostic significance of CRM+ after oesophagectomy and to identify endosonographic (endoluminal ultrasonography (EUS)) features that predict a threatened CRM+.

Methods:

Two hundred and sixty-nine consecutive patients underwent potentially curative oesophagectomy (103 surgery alone, 124 neoadjuvant chemotherapy (CS) and 42 chemoradiotherapy (CRTS)). Primary outcome measures were disease-free survival (DFS) and overall survival (OS).

Results:

CRM+ was reported in 98 (38.0%) of all, and in 90 (62.5%) of pT3 patients. Multivariate analysis of pathological factors revealed: lymphovascular invasion (HR 2.087, 95% CI 1.396–3.122, P<0.0001), CRM+ (HR 1.762, 95% CI 1.201–2.586, P=0.004) and lymph node metastasis count (HR 1.563, 95% CI 1.018–2.400, P=0.041) to be independently and significantly associated with DFS. Lymphovascular invasion (HR 2.160, 95% CI 1.432–3.259, P<0.001) and CRM+ (HR 1.514, 95% CI 1.000–2.292, P=0.050) were also independently and significantly associated with OS. Multivariate analysis revealed EUS T stage (T3 or T4, OR 24.313, 95% CI 7.438–79.476, P<0.0001) and use or not of CRTS (OR 0.116, 95% CI 0.035–0.382, P<0.0001) were independently and significantly associated with CRM+.

Conclusion:

A positive CRM was a better predictor of DFS and OS than standard pTNM stage.     

The preoperative lymphocyte to monocyte ratio predicts clinical outcome in patients with stage III colon cancer

Background:

Inflammation has a critical role in the pathogenesis and progression of cancer. The lymphocyte to monocyte ratio (LMR) could be shown to be prognostic in haematologic neoplasia. In this study, we analysed the LMR with clinical outcome in stage II and III colon cancer patients.

Methods:

Three hundred and seventy-two patients with stage II and III colon cancer were included in this retrospective study. Kaplan–Meier curves and multivariate Cox-regression analyses were calculated for time to recurrence (TTR) and overall survival (OS).

Results:

Including all patients, the elevated preoperative LMR was significantly associated with increased TTR and OS in multivariate analysis (HR: 0.47, 95%CI: 0.29–0.76, P=0.002; HR: 0.51, 95%CI: 0.31–0.83, P=0.007; respectively). In subanalyses, the association was limited to patients with stage III (HR: 0.40, 95%CI: 0.22–0.72, P=0.002), in contrast to patients with stage II (HR: 0.40, 95%CI: 0.28–1.66, P=0.397). When the subgroup of patients with ‘high-risk'' LMR⩽2.83 was analysed, no benefit of adjuvant 5-FU-based chemotherapy could be found (HR: 0.99; 95%CI: 0.60–1.63; P=0.953).

Conclusion:

The LMR might be an independent prognostic marker for TTR in stage III colon cancer patients. Our results further suggest that high-risk patients based on the LMR do not benefit from adjuvant chemotherapy. Independent validation of our findings is warranted.     

ERCC1, defective mismatch repair status as predictive biomarkers of survival for stage III colon cancer patients receiving oxaliplatin-based adjuvant chemotherapy

Background:

Excision repair cross-complementation group 1 (ERCC1) expression status has been identified as a candidate marker for predicting efficacy of oxaliplatin (OX) treatment for metastatic colorectal cancer (CRC) in several trials. Also, an association between expression of mismatch repair (MMR) genes and favourable postoperative survival in stage II CRC receiving 5-FU chemotherapy has been identified. It is unknown if the expression of ERCC1 protein and MMR status are associated with survival of stage III colon cancer receiving OX-based chemotherapy.

Methods:

Immunohistochemistry (IHC) analysis of the expression of MMR and ERCC1 was performed on tumour tissue of 255 patients with stage III colon cancer. In all, 95 patients received fluoropyrimidine-based chemotherapy and 160 patients received OX-based chemotherapy. A predictive model for 5-year disease-free survival (DFS) and overall survival (OS) was constructed using Kaplan–Meier analysis, logistic and Cox regression.

Results:

Patients who were treated with OX-based therapy with positive ERCC1 tumours had lower 5-year DFS (54%) and OS (60%) than those with negative ERCC1 tumours (72% and 78%, respectively; DFS HR: 1.98, 95% confidence interval (CI): 1.19–3.31, P=0.009; OS HR: 2.44, 95% CI: 1.37–4.34, P=0.02). Excision repair cross-complementation group 1 status did not impact DFS or OS in fluorouracil group (DFS HR: 1.16, 95% CI: 0.63–2.14, P=0.62; OS HR: 1.16, 95% CI: 0.63–2.14, P=0.63), whereas MMR status had no impact on DFS or OS in either group.

Conclusion:

Excision repair cross-complementation group 1 status is highly predictive of which patients will benefit from the addition of OX to 5-FU for stage III colon cancer. Mismatch repair status had no predictive value in this setting.     

Vascular endothelial growth factor D expression is a potential biomarker of bevacizumab benefit in colorectal cancer

Background:

Bevacizumab prolongs progression-free survival (PFS) in patients with metastatic colorectal cancer. We analysed the protein expression levels of vascular endothelial growth factor (VEGF) ligands and receptors to determine their prognostic and predictive effects.

Methods:

We graded expression of VEGF-A, VEGF-B, VEGF-C, VEGF-D, VEGF-R1, and VEGF-R2 to assess whether overexpression predicted bevacizumab resistance in samples from 268 of 471 patients randomised to capecitabine (C), capecitabine and bevacizumab (CB), or CB and mitomycin (CBM) in the MAX trial and extended the analysis to the CAIRO-2 population.

Results:

Patients with low expression of VEGF-D (0, 1+) benefited from bevacizumab treatment (PFS hazard ratio (HR) (C vs CB+CBM), 0.21; 95% CI, 0.08–0.55; overall survival (OS) HR, 0.35; 95% CI, 0.13–0.90). Patients with higher VEGF-D expression received less benefit (VEGF-D 2+ PFS HR, 0.67; 95% CI, 0.45–1.00; OS HR, 0.82; 95% CI, 0.52–1.30; VEGF-D 3+ PFS HR, 0.77; 95% CI, 0.50–1.17; OS HR, 1.28; 95% CI, 0.79–2.09) (P interaction <0.05). In CAIRO-2, there was no difference in PFS or OS according to VEGF-D expression.

Conclusions:

The predictive value of VEGF-D expression for bevacizumab may depend on the chemotherapy backbone used. Further evaluation is required before clinical utilisation.     

High expression of Toll-like receptor 4/myeloid differentiation factor 88 signals correlates with poor prognosis in colorectal cancer

Background:

The Toll-like receptor (TLR) 4 signalling pathway has been shown to have oncogenic effects in vitro and in vivo. To demonstrate the role of TLR4 signalling in colon tumourigenesis, we examined the expression of TLR4 and myeloid differentiation factor 88 (MyD88) in colorectal cancer (CRC).

Methods:

The expression of TLR4 and MyD88 in 108 CRC samples, 15 adenomas, and 15 normal mucosae was evaluated by immunohistochemistry, and the correlations between their immunoscores and clinicopathological variables, including disease-free survival (DFS) and overall survival (OS), were analysed.

Results:

Compared with normal mucosae and adenomas, 20% cancers displayed high expression of TLR4, and 23% cancers showed high expression of MyD88. The high expression of TLR4 and MyD88 was significantly correlated with liver metastasis (P=0.0001, P=0.0054). In univariate analysis, the high expression of TLR4 was significantly associated with shorter OS (hazard ratio (HR): 2.17; 95% confidence interval (95% CI): 1.15–4.07; P=0.015). The high expression of MyD88 expression was significantly associated with poor DFS and OS (HR: 2.33; 95% CI: 1.31–4.13; P=0.0038 and HR: 3.03; 95% CI: 1.67–5.48; P=0.0002). The high combined expression of TLR4 and MyD88 was also significantly associated with poor DFS and OS (HR: 2.25; 95% CI: 1.27–3.99; P=0.0053 and HR: 2.97; 95% CI: 1.64–5.38; P=0.0003). Multivariate analysis showed that high expressions of TLR4 (OS: adjusted HR: 1.88; 95% CI: 0.99–3.55; P=0.0298) and MyD88 (DFS: adjusted HR: 1.93; 95% CI: 1.01–3.67; P=0.0441; OS: adjusted HR: 2.25; 95% CI: 1.17–4.33; P=0.0112) were independent prognostic factors of OS. Furthermore, high co-expression of TLR4/MyD88 was strongly associated with both poor DFS and OS.

Conclusion:

Our findings suggest that high expression of TLR4 and MyD88 is associated with liver metastasis and is an independent predictor of poor prognosis in patients with CRC.     

Prognostic factors in elderly patients with malignant pleural mesothelioma: results of a multicenter survey

Background:

The incidence of malignant pleural mesothelioma (MPM) in elderly patients is increasing. There are no specific guidelines for their management.

Methods:

The clinical records of elderly patients (⩾70 years old) with MPM referred from January 2005 to November 2011 to six Italian Centres were reviewed. Age, gender, histology, International Mesothelioma Interest Group (IMIG) stage, Eastern Cooperative Oncology Group Performance Status (ECOG-PS), Charlson Comorbidity Index (CCI) and treatment modalities were analysed and correlated to overall survival (OS).

Results:

In total, 241 patients were identified. Charlson Comorbidity Index was ⩾1 in 92 patients (38%). Treatment was multimodality therapy including surgery in 18, chemotherapy alone in 180 (75%) and best supportive care in 43 cases (18%). Chemotherapy was mainly pemetrexed based. Median OS was 11.4 months. Non-epithelioid histology (HR 2.32; 95% CI 1.66–3.23, P<0.001), age ⩾75 years (HR 1.44; 95% CI 1.08–1.93, P=0.014), advanced (III–IV) stage (HR 1.47; 95% CI 1.09–1.98, P=0.011) and CCI⩾1 (HR 1.38; 95% CI 1.02–1.85, P=0.034) were associated to a shorter OS. Treatment with pemetrexed was associated with improved OS (HR 0.40; 95% CI 0.28–0.56, P<0.001).

Conclusions:

Non-epithelioid histology, age ⩾75 years, advanced IMIG stage and presence of comorbidities according to CCI were significant prognostic factors in elderly patients with MPM. Treatment with pemetrexed-based chemotherapy was feasible in this setting. Prospective dedicated trials in MPM elderly patients selected according to prognostic factors including comorbidity scales are warranted.     

Influence of pre-diagnostic cigarette smoking on colorectal cancer survival: overall and by tumour molecular phenotype

Background:

Smoking is a risk factor for incident colorectal cancer (CRC); however, it is unclear about its influence on survival after CRC diagnosis.

Methods:

A cohort of 706 CRC patients diagnosed from 1999 to 2003 in Newfoundland and Labrador, Canada, was followed for mortality and recurrence until April 2010. Smoking and other relevant data were collected by questionnaire after cancer diagnosis, using a referent period of ‘2 years before diagnosis'' to capture pre-diagnosis information. Molecular analyses of microsatellite instability (MSI) status and BRAF V600E mutation status were performed in tumour tissue using standard techniques. Multivariate hazard ratios (HRs) and 95% confidence intervals (CIs) were calculated with Cox proportional hazards regression, controlling for major prognostic factors.

Results:

Compared with never smokers, all-cause mortality (overall survival, OS) was higher for current (HR: 1.78; 95% CI: 1.04–3.06), but not for former (HR: 1.06; 95% CI: 0.71–1.59) smokers. The associations of cigarette smoking with the study outcomes were higher among patients with ⩾40 pack-years of smoking (OS: HR: 1.72; 95% CI: 1.03–2.85; disease-free survival (DFS: HR: 1.99; 95% CI: 1.25–3.19), those who smoked ⩾30 cigarettes per day (DFS: HR: 1.80; 95% CI: 1.22–2.67), and those with microsatellite stable (MSS) or MSI-low tumours (OS: HR: 1.38; 95% CI: 1.04–1.82 and DFS: HR: 1.32; 95% CI: 1.01–1.72). Potential heterogeneity was noted for sex (DFS HR: 1.68 for men and 1.01 for women: P for heterogeneity=0.04), and age at diagnosis (OS: HR: 1.11 for patients aged <60 and 1.69 for patients aged ⩾60: P for heterogeneity=0.03).

Conclusions:

Pre-diagnosis cigarette smoking is associated with worsened prognosis among patients with CRC.     

Androgen receptor expression predicts beneficial tamoxifen response in oestrogen receptor-α-negative breast cancer

Background:

Although the androgen receptor (AR) is frequently expressed in breast cancer, its relevance in the disease is not fully understood. In addition, the relevance of AR in determining tamoxifen treatment efficiency requires evaluation.

Purpose:

To investigate the tamoxifen predictive relevance of the AR protein expression in breast cancer.

Methods

Patients were randomised to tamoxifen 40 mg daily for 2 or 5 years or to no endocrine treatment. Mean follow-up was 15 years. Hazard ratios were calculated with recurrence-free survival as end point.

Results:

In patients with oestrogen receptor (ER)-negative tumours, expression of AR predicted decreased recurrence rate with tamoxifen (hazard ratio (HR)=0.34; 95% confidence interval (CI)=0.14–0.81; P=0.015), whereas the opposite was seen in the AR− group (HR=2.92; 95% CI=1.16–7.31; P=0.022). Interaction test was significant P<0.001. Patients with triple-negative and AR+ tumours benefitted from tamoxifen treatment (HR=0.12; 95% CI=0.014–0.95 P=0.044), whereas patients with AR− tumours had worse outcome when treated with tamoxifen (HR=3.98; 95% CI=1.32–12.03; P=0.014). Interaction test was significant P=0.003. Patients with ER+ tumours showed benefit from tamoxifen treatment regardless of AR expression.

Conclusions:

AR can predict tamoxifen treatment benefit in patients with ER− tumours and triple-negative breast cancer.     

Elevated preoperative neutrophil/lymphocyte ratio is associated with poor prognosis in soft-tissue sarcoma patients

Background:

Recent data indicate that tumour microenvironment, which is influenced by inflammatory cells, has a crucial role in cancer progression and clinical outcome of patients. In the present study, we investigated the prognostic relevance of preoperative neutrophil/lymphocyte (N/L) ratio on time to tumour recurrence (TTR) and overall survival (OS) in soft-tissue sarcoma (STS) patients who underwent curative surgical resection.

Methods:

In all, 260 STS patients were included in this retrospective study. Kaplan–Meier curves and multivariate Cox proportional models were calculated for TTR and OS.

Results:

In univariate analysis, elevated N/L ratio was significantly associated with decreased TTR (hazard ratio (HR), 2.32; 95% confidence interval (CI), 1.30–4.14; P=0.005) and remained significant in the multivariate analysis (HR, 1.98; 95%CI, 1.05–3.71; P=0.035). Patients with elevated N/L ratio showed a median TTR of 77.9 months. In contrast, patients with low N/L ratio had a median TTR of 99.1 months. Regarding OS, elevated N/L ratio was also significantly associated with decreased survival in univariate analysis (HR, 2.90; 95%CI, 1.82–4.61; P=0.001) and remained significant in multivariate analysis (HR, 1.88; 95%CI, 1.14–3.12; P=0.014).

Conclusion:

In conclusion, our findings suggest that an elevated preoperative N/L ratio predicts poor clinical outcome in STS patients and may serve as a cost-effective and broadly available independent prognostic biomarker.     

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.     

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.     

The impact of prior platinum therapy on survival in patients with metastatic urothelial cancer receiving vinflunine

Background:

A phase III trial demonstrated an overall survival advantage with the addition of vinflunine to best supportive care (BSC) in platinum-refractory advanced urothelial cancer. We subsequently examined the impact of an additional 2 years of survival follow-up and evaluated the influence of first-line platinum therapy on survival.

Methods:

The 357 eligible patients from the phase III study were categorised into two cohorts depending on prior cisplatin treatment: cisplatin or non-cisplatin. Survival was calculated using the Kaplan–Meier method.

Results:

The majority had received prior cisplatin (70.3%). Survival was higher in the cisplatin group (HR: 0.76; CI 95% 0.58–0.99; P=0.04) irrespective of treatment arm. Multivariate analysis including known prognostic factors (liver involvement, haemoglobin, performance status) and prior platinum administration did not show an independent effect of cisplatin. Vinflunine reduced the risk of death by 24% in the cisplatin-group (HR: 0.76; CI 95% 0.58–0.99; P=0.04) and by 35% in non-cisplatin patients (HR: 0.65; CI 95% 0.41–1.04; P=0.07).

Interpretation:

Differences in prognostic factors between patients who can receive prior cisplatin and those who cannot may explain the survival differences in patients who undergo second line therapy. Prior cisplatin administration did not diminish the subsequent benefit of vinflunine over BSC.     

High-risk features in radiation-associated breast angiosarcomas

Background:

Radiation-associated breast angiosarcoma (RT-AS) is an uncommon malignancy with an incidence of less than 1 % of all soft tissue sarcomas. The overall prognosis is quite dismal with high rates of recurrences and poor overall survival. There is an obvious paucity of data regarding clinical outcomes of patients with breast RT-AS.

Methods:

We identified all patients with RT-AS treated at the Memorial Sloan-Kettering Cancer Center between 1982–2011 and collected their correlative clinical information.

Results:

We identified 79 women with RT-AS with a median age of 68 (range 36–87). The median interval between radiation and development of RT-AS was 7 years (range 3–19). The median time to local and distant recurrence was 1.29 years (95 % CI 0.72–NA) and 2.48 years (95 % CI 1.29–NA), respectively. The median disease-specific survival was 2.97 years (95 % CI 2.21–NA). Independent predictors of worse disease-specific survival included age ⩾68 years (HR 3.11, 95 % CI 1.20–8.08, P=0.020) and deep tumors (HR 3.23, 95 % CI 1.02–10.21, P=0.046.)

Conclusion:

RT-AS has high local/distant recurrence rates, limited duration on standard chemotherapy and poor disease-specific survival.     

Efficacy and safety of sunitinib in elderly patients with metastatic renal cell carcinoma

Background:

We retrospectively analyzed sunitinib outcome as a function of age in metastatic renal cell carcinoma (mRCC) patients.

Methods:

Data were pooled from 1059 patients in six trials. Kaplan–Meier estimates of progression-free survival (PFS) and overall survival (OS) were compared by log-rank test between patients aged <70 (n=857; 81%) and ⩾70 (n=202; 19%) years.

Results:

In first-line patients, median PFS was comparable in younger and older patients, 9.9 vs 11.0 months, respectively (HR, 0.89; 95% CI: 0.73–1.09; P=0.2629), as was median OS, 23.6 vs 25.6 months (HR, 0.93; 95% CI: 0.74–1.18; P=0.5442). Similarly, in cytokine-refractory patients, median PFS was 8.1 vs 8.4 months (HR, 0.79; 95% CI: 0.49–1.28; P=0.3350), while median OS was 20.2 vs 15.8 months (HR, 1.14; 95% CI: 0.73–1.79; P=0.5657). Some treatment-emergent adverse events were significantly less common in younger vs older patients, including fatigue (60% vs 69%), cough (20% vs 29%), peripheral edema (17% vs 27%), anemia (18% vs 25%), decreased appetite (13% vs 29%), and thrombocytopenia (16% vs 25% all P<0.05). Hand–foot syndrome was more common in younger patients (32% vs 24%).

Conclusions:

Advanced age should not be a deterrent to sunitinib therapy and elderly patients may achieve additional clinical benefit.     

Supplemental folic acid in pregnancy and childhood cancer risk

Background:

We investigated the association between supplemental folic acid in pregnancy and childhood cancer in a nation-wide study of 687 406 live births in Norway, 1999–2010, and 799 children diagnosed later with cancer.

Methods:

Adjusted hazard ratios (HRs) compared cancer risk in children by approximated periconceptional folic acid levels (folic acid tablets and multivitamins (0.6 mg), only folic acid (0.4 mg), only multivitamins (0.2 mg)) and cancer risk in unexposed.

Results:

Any folic acid levels were not associated with leukemia (e.g., high-level folic acid HR 1.25; 95% CI 0.89–1.76, P_Trend 0.20), lymphoma (HR 0.96; 95% CI 0.42–2.21, P_Trend 0.51), central nervous system tumours (HR 0.68; 95% CI 0.42–1.10, P_Trend 0.32), neuroblastoma (HR 1.05; 95% CI 0.53–2.06, P_Trend 0.85), Wilms'' tumour (HR 1.16; 95% CI 0.52–2.58, P_Trend 0.76), or soft-tissue tumours (HR 0.77; 95% CI 0.34–1.75, P_Trend 0.90).

Conclusions:

Folic acid supplementation was not associated with risk of major childhood cancers.     

The elevated preoperative platelet-to-lymphocyte ratio predicts poor prognosis in breast cancer patients

Background:

The elevation of the platelet-to-lymphocyte ratio (PLR), an easily applicable blood test based on platelet and lymphocyte counts has been associated with poor prognosis in patients with different types of cancer. The present study was aimed to investigate the prognostic significance of the preoperative PLR in a large cohort of breast cancer patients.

Methods:

Data from 793 consecutive non-metastatic breast cancer patients, treated between 1999 and 2004, were evaluated retrospectively. The optimal cutoff values for the PLR were calculated using receiver operating curve analysis. Cancer-specific survival (CSS), overall survival (OS) as well as distant metastasis-free survival (DMFS) were assessed using the Kaplan–Meier method. To evaluate the independent prognostic significance of PLR, multivariable Cox regression models were applied for all three different end points.

Results:

Univariable analysis revealed a significant association between the elevated preoperative PLR and CSS (hazard ratio (HR): 2.75, 95% confidence interval (CI): 1.57–4.83, P<0.001) that remained statistically significant in multivariable analysis (HR: 2.03, 95% CI: 1.03–4.02, P=0.042). An increased PLR was also significantly associated with decreased OS in univariable (HR: 2.45, 95% CI: 1.43–4.20, P=0.001) and in multivariable analysis (HR: 1.92, 95% CI: 1.01–3.67, P=0.047). Furthermore, univariable analysis showed a significant impact of increased PLR on DMFS (HR: 2.02, 95% CI: 1.18–3.44, P=0.010). Subgroup analysis revealed significant associations of the elevated PLR on the primary end point CSS for all breast cancer subtypes. This association retained its significance in multivariable analysis in patients with luminal B tumours (HR: 2.538, 95% CI: 1.043–6.177, P=0.040).

Conclusions:

In this study, we identified the preoperative PLR as an independent prognostic marker for survival in breast cancer patients. Independent validation of our findings is needed.     

Employment and social benefits up to 10 years after breast cancer diagnosis: a population-based study

Background:

Little is known about employment outcomes after breast cancer (BC) beyond the first years after treatment.

Methods:

Employment outcomes were compared with a general population comparison group (N=91 593) up to 10 years after BC for 26 120 patients, diagnosed before age 55 between 2000–2005, with income and social benefits data from Statistics Netherlands. Treatment effects were studied in 14 916 patients, with information on BC recurrences and new cancer events.

Results:

BC survivors experienced higher risk of losing paid employment (Hazard Ratio (HR): 1.6, 95% Confidence Interval (95% CI) 1.4–1.8) or any work-related event up to 5–7 years (HR 1.5, 95% CI 1.3–1.6) and of receiving disability benefits up to 10 years after diagnosis (HR 2.0, 95% CI 1.6–2.5), with higher risks for younger patients. Axillary lymph node dissection increased risk of disability benefits (HR 1.5, 95% CI 1.4–1.7) or losing paid employment (HR 1.3, 95% CI 1.2–1.5) during the first 5 years of follow-up. Risk of disability benefits was increased among patients receiving mastectomy and radiotherapy (HR 1.2; 95% CI 1.1–1.3) and after chemotherapy (HR 1.7; 95% CI 1.5–1.9) during the first 5 years after diagnosis.

Conclusions:

BC treatment at least partly explains the increased risk of adverse employment outcomes up to 10 years after BC.     

High plasma fibrinogen level represents an independent negative prognostic factor regarding cancer-specific,metastasis-free,as well as overall survival in a European cohort of non-metastatic renal cell carcinoma patients

Background:

In recent years, plasma fibrinogen has been ascribed an important role in the pathophysiology of tumour cell invasion and metastases. A relatively small-scale study has indicated that plasma fibrinogen levels may serve as a prognostic factor for predicting clinical outcomes in non-metastatic renal cell carcinoma (RCC) patients.

Methods:

Data from 994 consecutive non-metastatic RCC patients, operated between 2000 and 2010 at a single, tertiary academic centre, were evaluated. Analyses of plasma fibrinogen levels were performed one day before the surgical interventions. Patients were categorised using a cut-off value of 466 mg dl⁻¹ according to a calculation by receiver-operating curve analysis. Cancer-specific (CSS), metastasis-free (MFS), as well as overall survival (OS) were assessed using the Kaplan–Meier method. To evaluate the independent prognostic impact of plasma fibrinogen level, a multivariable Cox regression model was performed for all three different endpoints.

Results:

High plasma fibrinogen levels were associated with various well-established prognostic factors, including age, advanced tumour stage, tumour grade and histologic tumour necrosis (all P<0.05). Furthermore, in multivariable analysis, a high plasma fibrinogen level was statistically significantly associated with a poor outcome for patients'' CSS (hazard ratio (HR): 2.47, 95% confidence interval (CI): 1.49–4.11, P<0.001), MFS (HR: 2.15, 95% CI: 1.44–3.22, P<0.001) and OS (HR: 2.48, 95% CI: 1.80–3.40, P<0.001).

Conclusion:

A high plasma fibrinogen level seems to represent a strong and independent negative prognostic factor regarding CSS, MFS and OS in non-metastatic RCC patients. Thus, this easily determinable laboratory value should be considered as an additional prognostic factor for RCC patients'' individual risk assessment.     

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.