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.     

Prognostic value of ABO blood group in patients with surgically resected colon cancer

Background:

Previous studies supported a link between the ABO blood type and survival for several types of malignancies. Nonetheless, the relationship between ABO blood type and survival in colon cancer patients has not been rigorously evaluated. The goal of this retrospective analysis was to discern the correlations between ABO blood group and colon cancer survival.

Methods:

A total of 1555 colon cancer patients that underwent curative-intent surgery between October 1995 and June 2002 were eligible for this study. The primary outcomes measured were the association between ABO blood group and patient survival.

Results:

Compared with patients with non-AB blood types (blood types A, B, and O), patients with blood type AB were more likely to have better survival. The mean overall survival (OS) of the blood type AB patients was 113.9 months, whereas the mean OS of the non-AB blood type patients was significantly lower, 106.1 months (P<0.001, log-rank test). Compared with patients with blood type AB, the hazard ratios for patients with A, B, and O were 4.37 (95% confidence interval (95% CI), 2.65–7.20), 2.99 (95% CI, 1.81–4.96), and 2.78 (95% CI, 1.69–4.56), respectively.

Conclusions:

Blood type AB is a favourable prognostic factor for patients with colon cancer.     

Prognostic significance of PET assessment of metabolic response to therapy in oesophageal squamous cell carcinoma

Objectives:

The role of maximum standard uptake value (SUVmax) at baseline and after induction chemotherapy (CT) on positron emission tomography (PET) as an imaging biomarker has not been well established in oesophageal squamous cell carcinoma (SCC). In this retrospective analysis, we investigated the prognostic significance of various PET metrics in oesophageal SCC patients treated with induction chemotherapy followed by concurrent chemoradiotherapy (CRT).

Methods:

A total of 57 patients were treated with CRT; 52 patients received induction chemotherapy and 10 patients underwent surgery following CRT. Scans were independently analysed by a nuclear medicine physician blinded to patient outcome. Using region of interest analysis, SUVmax and metabolic tumour volume (MTV) were calculated for the index lesion and lymph node metastases in each patient. Kaplan–Meier analysis was used to evaluate overall survival (OS), disease-free survival (DFS), local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS). Cox proportional hazards regression was used to assess correlation between outcomes and PET metrics.

Results:

Median follow-up for those who are alive was 4.4 years, with a median survival for all patients of 2.9 years. The 3-year OS, DFS, DMFS and LRFS rates were 47, 40, 44 and 36%, respectively. Using a pre-established cutoff of a 35% decrease in SUVmax from baseline to post-induction PET, 3-year OS for responders (⩾35% decrease from baseline) was 64%, whereas non-responders (<35% decrease from baseline) had a 3-year OS of 15% (P=0.004).

Conclusions:

The pre-specified 35% decrease in SUVmax after induction chemotherapy was prognostic for OS. Baseline and post-induction PET metrics provide prognostic information for oesophageal SCC.     

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.     

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.     

Combining plasma Epstein-Barr virus DNA and nodal maximal standard uptake values of 18F-fluoro-2-deoxy-D-glucose positron emission tomography improved prognostic stratification to predict distant metastasis for locoregionally advanced nasopharyngeal carcinoma

Background

This study aimed to evaluate the value of combining the nodal maximal standard uptake values (SUVmax) of ¹⁸ F-fluoro-2-deoxy-D-glucose positron emission tomography with Epstein-Barr virus DNA(EBV DNA) levels to predict distant metastasis for nasopharyngeal carcinoma (NPC) patients

Patients and Methods

Eight hundred seventy-four patients with stage III-IVa-b NPC were evaluated for the effects of combining SUVmax and EBV DNA levels on distant metastasis-free survival (DMFS), disease-free survival (DFS) and overall survival (OS).

Results

The optimal cutoff value was 6,220 copies/mL for EBV DNA and 7.5 for SUVmax-N. Patients with lower EBV DNA levels or SUVmax-N had a significantly better 3-year DMFS, DFS, and OS. Patients were divided into four groups based on EBV DNA and SUVmax-N, as follows: low EBV DNA and low SUVmax-N (LL), low EBV DNA and high SUVmax-N (LH), high EBV DNA and low SUVmax-N (HL), and high EBV DNA and high SUVmax-N (HH). There were significant differences between the four mentioned groups in 3-year DMFS: 95.7%, 92.2%, 92.3%, and 80.1%, respectively (P^trend < 0.001). When looking at the disease stage, the 3-year DMFS in group LL, LH, HL, HH were 94.2%, 92.9%, 95.0%, and 81.1%, respectively, in stage III patients (P^trend < 0.001) and 92.7%, 87.2%, 86.3%, and 77.0% in stage IVa–b patients (P^trend = 0.026).

Conclusion

Pretreatment EBV DNA and SUVmax of neck lymph nodes were independent prognostic factors for distant metastasis in NPC patients. Combining EBV DNA and SUVmax-N led to an improved risk stratification for distant metastasis in advanced-stage disease.     

Pro-angiogenic cytokines for prediction of outcomes in patients with advanced hepatocellular carcinoma

Background:

We previously reported that expressions of the pro-angiogenic cytokines angiopoietin-2 (Ang-2), follistatin, granulocyte colony-stimulating factor, hepatocyte growth factor, leptin, platelet-derived growth factor-BB, platelet endothelial cell adhesion molecule-1, and vascular endothelial growth factor were associated with the response to sorafenib in patients with advanced hepatocellular carcinoma (HCC). The aim of the present study is to examine the same relationship in a larger cohort.

Methods:

In the current retrospective cohort study, we measured serum levels of the eightcytokines in 120 consecutive HCC patients who were treated with sorafenib. We evaluated the effects of increased expression of serum cytokines on progression-free survival (PFS) and overall survival (OS).

Results:

Elevated expression of Ang-2 correlated both with significantly shorter PFS (hazard ratio (HR), 1.84; 95% confidence interval (CI), 1.21–2.81), and OS (HR, 1.95; 95% CI, 1.21–3.17). Patients with more than three cytokines expressed above the median similarly had significantly shorter PFS (HR, 1.98; 95% CI, 1.30–3.06) and OS (HR, 1.94; 95% CI, 1.19–3.22). Differences in OS were evident in cases with the evidence of macroscopic vascular invasion or extrahepatic metastasis.

Conclusion:

High expression of Ang-2 or more than cytokines in serum is associated with poor PFS and OS in HCC patients treated with sorafenib.     

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.     

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.     

Head and neck cancer relapse after chemoradiotherapy correlates with CD163+ macrophages in primary tumour and CD11b+ myeloid cells in recurrences

Background:

We investigated the prognostic role of tumour-associated macrophages (TAMs) in patients with head and neck squamous cell carcinoma (HNSCC) treated with definitive chemoradiotherapy (CRT).

Methods:

The expression of CD68+, CD163+ and CD11b+ cells was assessed using immunohistochemistry in n=106 pre-treatment tumour biopsy samples and was correlated with clinicopathological characteristics, including T-stage, N-stage, grading, tumour localisation, age and sex as well as local failure-free survival (LFFS), distant metastases-free survival (DMFS), progression-free (PFS), and overall survival (OS). Finally, TAMs expression and vessel density (CD31) were examined in n=12 available early local recurrence samples and compared with their matched primary tumours . The diagnostic images and radiotherapy plans of these 12 patients were also analysed. All local recurrences occurred in the high radiation dose region (⩾70 Gy).

Results:

With a median follow-up of 40 months, OS at 2 years was 60.5%. High CD163 expression in primary tumours was associated with decreased OS (P=0.010), PFS (P=0.033), LFFS (P=0.036) and DMFS (P=0.038) in multivariate analysis. CD163 demonstrated a strong prognostic value only in human papillomavirus (p16^INK4)-negative patients. Early local recurrence specimens demonstrated a significantly increased infiltration of CD11b+ myeloid cells (P=0.0097) but decreased CD31-positive vessel density (P=0.0004) compared with their matched primary samples.

Conclusions:

Altogether, baseline CD163 expression predicts for an unfavourable clinical outcome in HNSCC after definitive CRT. Early local recurrences showed increased infiltration by CD11b+ cells. These data provide important insight on the role of TAMs in mediating response to CRT in patients with HNSCC.     

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.     

Population-based comparison of prognostic factors in invasive micropapillary and invasive ductal carcinoma of the breast

Background:

Invasive micropapillary carcinoma (IMPC) is a variant of breast carcinoma with a higher propensity for lymph node metastases compared with invasive ductal carcinoma (IDC).

Methods:

Retrospective analysis of 636 IMPC and 297 735 IDC cases in the Surveillance, Epidemiology and End Results database comparing disease-specific survival (DSS) and overall survival (OS) between IMPC and IDC.

Results:

A higher percentage of IMPC cases (52.0%) had nodal metastases compared with IDC cases (34.6%). The 5-year DSS and OS for IMPC was 91.8% and 82.9%, respectively compared with 88.6% and 80.5% for IDC, respectively. For both IMPC and IDC, oestrogen-receptor positivity was associated with better survival, while having four or more positive lymph nodes or larger tumour size correlated with worse survival. Radiotherapy provided a survival benefit for both histological types.

Conclusions:

Despite IMPC''s higher propensity for lymph node metastasis, IMPC has DSS and OS that compare favourably with IDC.     

Tumour-infiltrating lymphocytes predict response to definitive chemoradiotherapy in head and neck cancer

Background:

We aimed to investigate the prognostic value of tumour-infiltrating lymphocytes'' (TILs) expression in pretreatment specimens from patients with head and neck squamous cell carcinoma (HNSCC) treated with definitive chemoradiotherapy (CRT).

Methods:

The prevalence of CD3+, CD8+, CD4+ and FOXP3+ TILs was assessed using immunohistochemistry in tumour tissue obtained from 101 patients before CRT and was correlated with clinicopathological characteristics as well as local failure-free- (LFFS), distant metastases free- (DMFS), progression-free (PFS) and overall survival (OS). Survival curves were measured using the Kaplan–Meier method, and differences in survival between the groups were estimated using the log-rank test. Prognostic effects of TIL subset density were determined using the Cox regression analysis.

Results:

With a mean follow-up of 25 months (range, 2.3–63 months), OS at 2 years was 57.4% for the entire cohort. Patients with high immunohistochemical CD3 and CD8 expression had significantly increased OS (P=0.024 and P=0.028), PFS (P=0.044 and P=0.047) and DMFS (P=0.021 and P=0.026) but not LFFS (P=0.90 and P=0.104) in multivariate analysis that included predictive clinicopathologic factors, such as age, sex, T-stage, N-stage, tumour grading and localisation. Neither CD4 nor FOXP3 expression showed significance for the clinical outcome. The lower N-stage was associated with improved OS in the multivariate analysis (P=0.049).

Conclusion:

The positive correlation between a high number of infiltrating CD3+ and CD8+ cells and clinical outcome indicates that TILs may have a beneficial role in HNSCC patients and may serve as a biomarker to identify patients likely to benefit from definitive CRT.     

Aromatase inhibitors with or without gonadotropin-releasing hormone analogue in metastatic male breast cancer: a case series

Background:

Data regarding the safety and effectiveness of aromatase inhibitors (AIs) as monotherapy or combined with gonadotropin-releasing hormone (GnRH) analogue in male breast cancer are scarce.

Methods:

In this retrospective chart review, cases of male breast cancer patients treated with AIs with or without a GnRH analogue were evaluated.

Results:

Twenty-three men were included into this case series. Aromatase inhibitors in combination with or without a GnRH analogue were given as first-line therapy in 60.9% and as second-line therapy in 39.1% of patients, respectively. All patients had visceral metastases, whereas in five of them bone lesions coexisted. In all cases AIs were tolerated well, and no case of grade 3 and 4 adverse events was reported. A partial response was observed in 26.1% of patients and stable disease in 56.5%. Median overall survival (OS) was 39 months and median progression-free survival (PFS) was 13 months. Regarding OS and PFS, no significant effects of GnRH analogue co-administration or type of AI were noted.

Conclusion:

Our study shows that AIs with or without GnRH analogues may represent an effective and safe treatment option for hormone-receptor positive, pretreated, metastatic, male breast cancer patients.     

Inflammation as a validated prognostic determinant in carcinoma of unknown primary site

Background:

Carcinoma of unknown primary (CUP) is a clinical presentation with a poor prognosis. Inflammation-based prognostic systems are stage-independent prognostic predictors in various malignancies. We aimed to assess the accuracy of the modified Glasgow Prognostic Score (mGPS), neutrophil/lymphocyte ratio (NLR) and platelet/lymphocyte ratio (PLR) as objective prognostic models in CUP.

Methods:

We derived inflammatory scores in 60 consecutive CUP referrals to the Imperial College oncology unit between 1996 and 2011. Patient demographics, treatment and staging data and full blood profiles were collected. An independent cohort of 179 patients presenting to the Taipei Veterens Hospital between 2000 and 2009 were used as a ‘validation'' data set. Uni- and multivariate survival analysis was used to predict the overall survival (OS).

Results:

Sixty patients were included: median age 61 (range: 33–86); 51% men; median OS 5.9 months (0.7–42.9); 88% with distant metastases. On univariate analysis NLR >5 (P=0.04) and mGPS (score 1–2) (P=0.03) correlated with OS. Multivariate analysis demonstrated significant hazard ratios for NLR; 2.02 (CI 1.0–4.1) (P=0.04) and mGPS; 1.52 (CI 1.0–2.3) (P=0.03). These findings were reinforced by analysis of the validation data.

Conclusion:

NLR and mGPS are independent, externally validated prognostic markers in CUP, with superior objectivity compared with performance status.     

Using multiple cytokines to predict hepatocellular carcinoma recurrence in two patient cohorts

Background:

Cytokines are tightly linked to the carcinogenesis, development and prognosis of hepatocellular carcinoma (HCC). We determined the prognostic value of 39 circulating cytokines in HCC patients after radical resection and then developed a novel cytokine-based prognostic classifier (CBPC) for the prediction of patient prognosis.

Methods:

A total of 179 patients were divided into two cohorts based on the date of radical resection. Thirty-nine cytokines were simultaneously analysed in patient serum samples using multiplex bead-based Luminex technology. Support vector machine-based methods and Cox proportional hazard models were used to develop a CBPC from the training cohort, which was then validated in the validation cohort.

Results:

Among seven cytokines significantly correlating with the disease-free survival (DFS) in the training cohort, six of them were validated to be significant prognostic factors to predict DFS and overall survival (OS) in the validation cohort, namely fibroblast growth factor 2 (FGF-2), growth-regulated oncogene (GRO), interleukin 8 (IL-8), interferon gamma-induced protein 10 (IP-10), vascular endothelial growth factor (VEGF), and interferon alpha-2 (IFN-α2). By integrating six cytokines and three clinical characteristics, we developed a CBPC to predict the recurrence and 3-year OS of HCC patients (sensitivity, 0.648; specificity, 0.918). In the validation cohort, the CBPC were confirmed to have significant predictive power for predicting tumour recurrence and OS (sensitivity, 0.585; specificity, 0.857). Interestingly, IFN-α2 was the only cytokine being independent prognostic factor in both patient cohorts.

Conclusion:

Our study verifies the presence of specific cytokine–phenotype associations with patient prognosis in HCC. The CBPC developed include multiple circulating cytokines and may serve as a novel screening approach for identifying HCC patients with a high risk of post-resection recurrence and shorter OS. These individuals may also be suitable for cytokine-targeted therapies.     

High CXC chemokine receptor 4 expression is an adverse prognostic factor in patients with clear-cell renal cell carcinoma

Background:

Aberrant CXC chemokine receptor 4 (CXCR4) expressions in malignant tissues have been reported; however, its role in kidney cancer prognosis remains unknown. The aim of this study was to determine the prognostic value of CXCR4 expression in patients with clear-cell renal cell carcinoma (ccRCC).

Methods:

The study included 225 patients with ccRCC. The cohort was split into a training set (n=125) and a validation set (n=100). CXC chemokine receptor 4 expression was analysed by immunohistochemical staining and its correlations with clinicopathologic features and prognosis were evaluated.

Results:

CXCR4-staining intensity increased gradually accompanied with disease progression from TNM stages I to IV in 225 patients with ccRCC. Moreover, high CXCR4 expression indicated reduced overall survival (OS) in the training (P<0.001) and validation (P<0.001) sets, especially for patients with early-stage (TNM stage I+II) diseases. Furthermore, CXCR4 expression was identified as an independent prognostic factor for OS, and combining TNM stage with CXCR4 expression showed a better prognostic value for OS in both sets.

Conclusions:

High CXCR4 expression, an independent adverse prognostic factor, could be combined with TNM stage to generate a predictive nomogram for clinical outcome in patients with ccRCC.     

Progesterone receptor expression is an independent prognostic variable in early breast cancer: a population-based study

Background:

Progesterone receptor (PR) expression assessment in early invasive breast cancer remains controversial. This study sought to re-evaluate PR expression as a potential therapeutic guide in early breast cancer; particularly in oestrogen receptor (ER)-positive, lymph node (LN)-negative disease.

Methods:

A population cohort of 1074 patients presenting to a single Cancer Centre over 4 years (2000–2004) underwent surgery for primary invasive breast cancer with curative intent. Prospective data collection included patient demographics, pathology, ER and PR expression, HER2 status, adjuvant chemotherapy and endocrine therapy. Progesterone receptor expression was compared with (all causes) overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS).

Results:

Overall survival was 71.0% and BCSS was 83.0% at median follow-up of 8.34 years. Absent PR expression was significantly associated with poorer prognosis for OS, BCSS and DFS (P<0.0001, log-rank), even within the ER-positive, LN-negative group (hazard ratio for BCSS 3.17, 95% CI 1.43–7.01) and was not influenced by endocrine therapy. Cox''s regression analysis demonstrated that PR expression was an independent prognostic variable.

Conclusion:

Absence of PR expression is a powerful, independent prognostic variable in operable, primary breast cancer even in ER-positive, LN-negative patients receiving endocrine therapy. Absence of PR expression should be re-evaluated as a biomarker for poor prognosis in ER-positive breast cancer and such patients considered for additional systemic therapy.     

Evaluation of prognostic factors in liver-limited metastatic colorectal cancer: a preplanned analysis of the FIRE-1 trial

Background:

Liver-limited disease (LLD) denotes a specific subgroup of metastatic colorectal cancer (mCRC) patients.

Patients and Methods:

A total of 479 patients with unresectable mCRC from an irinotecan-based randomised phase III trial were evaluated. Patients with LLD and non-LLD and hepatic resection were differentiated. Based on baseline patient characteristic, prognostic factors for hepatic resection were evaluated. Furthermore, prognostic factors for median overall survival (OS) were estimated via Cox regression in LLD patients.

Results:

Secondary liver resection was performed in 38 out of 479 patients (resection rate: 7.9%). Prognostic factors for hepatic resection were LLD, lactate dehydrogenase (LDH), node-negative primary, alkaline phosphatase (AP) and Karnofsky performance status (PS). Median OS was significantly increased after hepatic resection (48 months), whereas OS in LLD (17 months) and non-LLD (19 months) was comparable in non-resected patients. With the inapplicability of Koehne''s risk classification in LLD patients, a new score based on only the independent prognostic factors LDH and white blood cell (WBC) provided markedly improved information on the outcome.

Conclusion:

Patients undergoing hepatic resection showed favourable long-term survival, whereas non-resected LLD patients and non-LLD patients did not differ with regard to progression-free survival and OS. The LDH levels and WBC count were confirmed as prognostic factors and provide a useful and simple score for OS-related risk stratification also in LLD.     

Mean overall survival gain with aflibercept plus FOLFIRI vs placebo plus FOLFIRI in patients with previously treated metastatic colorectal cancer

Background:

Mean survival in cancer trials can be estimated with statistical techniques to extrapolate study survival curves. This methodology was applied to data from the VELOUR trial, where use of the novel biologic aflibercept (ziv-aflibercept in the United States) in combination with fluorouracil+leucovorin+irinotecan (FOLFIRI), had significantly increased median overall survival (OS) by 1.44 months, vs placebo plus FOLFIRI in patients with metastatic colorectal cancer (mCRC) resistant to, or that had progressed following, an oxaliplatin-containing regimen.

Methods:

Parametric survival analyses were used to identify distributions with the best fit to the empirical VELOUR data. Mean OS for the two treatment groups (and pre-defined subgroups) was calculated from the fitted curves over a 15-year survival period.

Results:

Overall, the log-logistic distribution was the best-fitting for both treatment arms and, with it, the estimated difference in mean OS over 15 years between aflibercept+FOLFIRI and placebo+FOLFIRI was 4.7 months. In addition, the survival advantage with aflibercept was at least 3 months for the ITT population, whichever distribution was used to extrapolate survival.

Conclusion:

Extrapolation of survival curves suggests the mean OS difference for aflibercept in the VELOUR trial is at least 3 months in the ITT population and selected subgroups.