Platelet–lymphocyte and neutrophil–lymphocyte ratios are prognostic but not predictive of response to abiraterone acetate in metastatic castration-resistant prostate cancer

Purpose

Recently neutrophil–lymphocyte ratio (NLR) and platelet–lymphocyte ratio (PLR) have been reported to be inflammatory parameters that confer poorer outcome in metastatic castration-resistant prostate cancer (mCPRPC). However, these ratios have not been analyzed in patients treated with abiraterone acetate. We explored the relationship between different values of PLR and NLR and survival in mCPRCP treated with abiraterone and their possible relation with a prostate specific antigen (PSA) response.

Methods

We retrospectively analyzed 101 patients with mCRPC treated with abiraterone from January of 2012 to November of 2015 in two different hospitals. A cut-off value of 5 for NLR and 150 for PLR were used to compare survival by Kaplan–Meier method. Moreover, an association between these cut-off values and the PSA response was analyzed by a χ ² test.

Results

In the case of NLR, the median DFS were 12, 1 months for NLR <5 and 7 months for NLR ≥5, p = 0.061. The median OS were 23.9 months for NLR <5 and 16.3 months for NLR ≥5, p = 0.046. In the case of PLR, the median DFS were 11.8 months for PLR <150 and 10.6 months for PLR ≥150, p = 0.549. The median OS were 27.4 months for PLR <150 and 15.9 months for PLR ≥150, p = 0.005. It was not observed a correlation between the different cut-off values of PLR or NLR and a PSA response ≥25% (p = 0.31).

Conclusions

It is shown a better prognostic relationship between PLR and NLR low values and OS that is statistically significant in mCPRC patients treated with abiraterone. Furthermore, it was not shown a relation between PLR and NLR values and PSA response.

     

The impact of body mass index on oncological outcomes in colorectal cancer patients with curative intent

Background

Excess body weight is associated with a risk of several malignancies, including colon cancer. However, the oncological significance of evaluating body mass index (BMI) preoperatively in colorectal cancer (CRC) patients undergoing curative surgery has not been fully evaluated.

Methods

Clinicopathological findings including BMI and laboratory data [carcinoembryonic antigen (CEA) and neutrophil/lymphocyte ratio (NLR)] from 358 curative CRC patients (open surgery group: n = 157; laparoscopic surgery group: n = 201) were assessed as indicators of survival outcome. BMI <20 was defined as underweight in both groups.

Results

Not all categories of pathological findings were associated with BMI in both groups. Patients with BMI <20 showed significant poorer overall survival (OS) in the open surgery group. In addition, patients with BMI <20 in the laparoscopic surgery group were also significantly worse in OS and disease-free survival (DFS). Furthermore, multivariate analysis demonstrated that BMI was validated as independent predictors for OS and DFS in both groups. BMI had a significant negative correlation with NLR, which reflects host immune response in both groups.

Conclusions

Lower BMI is a promising predictor of recurrence and prognosis in curative CRC patients.

     

Inflammatory Indexes as Prognostic and Predictive Factors in Ovarian Cancer Treated with Chemotherapy Alone or Together with Bevacizumab. A Multicenter,Retrospective Analysis by the MITO Group (MITO 24)

Background

The variability in progression-free survival (PFS) and overall survival (OS) among patients with epithelial ovarian cancer (EOC) makes it difficult to reliably predict outcomes. A predictive biomarker of bevacizumab efficacy as first-line therapy in EOC is still lacking.

Objective

The MITO group conducted a multicenter, retrospective study (MITO 24) to investigate the role of inflammatory indexes as prognostic factors and predictors of treatment efficacy in FIGO stage III–IV EOC patients treated with first-line chemotherapy alone or in combination with bevacizumab.

Patients and Methods

Of the 375 patients recruited, 301 received chemotherapy alone and 74 received chemotherapy with bevacizumab. The pre-treatment neutrophil-to-lymphocyte ratio (NLR), platelet-to-lymphocyte ratio (PLR), and systemic immune inflammation index (SII) were evaluated to identify a potential correlation with PFS and OS in both the overall population and the two treatment arms.

Results

In the overall population, the PFS and OS were significantly longer in patients with low inflammatory indexes (p?<?0.0001). In multivariate analyses, the NLR was significantly associated with OS (p?=?0.016), and the PLR was significantly associated with PFS (p?=?0.024). Inflammatory indexes were significantly correlated with patient prognosis in the chemotherapy-alone group (p?<?0.0001). Patients in the chemotherapy with bevacizumab group with a high NLR had a higher PFS and OS (p?=?0.026 and p?=?0.029, respectively) than those in the chemotherapy-alone group. Conversely, PFS and OS were significantly poorer in patients with a high SII (p?=?0.024 and p?=?0.017, respectively).

Conclusion

Our results suggest that bevacizumab improves clinical outcome in patients with a high NLR but may be detrimental in those with a high SII.

     

A critical prognostic analysis of neutrophil–lymphocyte ratio for patients undergoing nephroureterectomy due to upper urinary tract urothelial carcinoma

Background

To determine preoperative serum complete blood count parameters that affects survival of patients who underwent surgery for upper urinary tract urothelial cancer (UUT-UC).

Methods

Since 1990, 150 patients underwent nephroureterectomy with bladder cuff excision for UUT-UC at Hacettepe University. Patients with a history of muscle-invasive bladder cancer, adjuvant chemotherapy or metastasis at the time of diagnosis were excluded. One hundred and thirteen patients without infective symptoms and with a full set of serum data were evaluated retrospectively. Effects of the neutrophil–lymphocyte ratio (NLR), lymphocyte–monocyte ratio (LMR), platelet–lymphocyte ratio (PLR), and leukocyte count on disease-free survival (DFS) and progression-free survival (PFS) were investigated. Threshold values for each parameter to predict PFS were calculated.

Results

The mean age and median follow-up were 63.7 ± 11.1 years and 34 (3–186) months, respectively. Male to female ratio was 86/27. The 5-years PFS (bladder recurrence was excluded) and DFS were 59.6 and 38.4%, respectively. In multivariate analysis, NLR was independent prognostic factor for PFS and DFS (p = 0.006 and p = 0.021, respectively) while LMR was prognostic only for PFS (p = 0.037).

Conclusion

For UUT-UC, NLR is a prognostic factor for PFS and DFS, while LMR is a prognostic indicator for PFS in present series.

     

Usefulness of lymphocyte-to-monocyte,neutrophil-to-monocyte and neutrophil-to-lymphocyte ratios as prognostic markers in breast cancer patients treated with neoadjuvant chemotherapy

Background

Nowadays, neoadjuvant chemotherapy (nCT) in breast cancer is more and more standardized, not only in advanced tumours but also in those for which there is an attempt to achieve breast-conserving surgery. In literature, we can find evidences of the relationship between several types of tumours and systemic inflammatory response. Our objective is to analyse the prognostic value of blood parameters (lymphocytes, neutrophils, monocytes, lymphocyte-to-monocyte ratio (LMR), neutrophil-to-monocyte ratio (NMR) and neutrophil-to-lymphocyte ratio (NLR) in breast cancer (BC) patients treated with nCT.

Methods

A retrospective cohort of 150 breast cancer patients treated with nCT and subsequently with surgery was analysed. Data about the patients, histology, response to chemotherapy and peripheral blood values of lymphocytes, monocytes and neutrophils was collected, and used to calculate the LMR, NMR and NLR. Univariate and multivariate analyses were performed for the variables to see the relationship of the ratios to disease-free survival (DFS) and overall survival (OS).

Results

Patients with high LMR (≥5.46) and low NLR (<3.33) were associated with a lower percentage of relapse (P = 0.048 and P = 0.015, respectively) and, above all, NLR was associated with a better survival (P = 0.024), being those factors that predict a good progress.

Conclusion

High LMR and low NLR can be considered as favourable prognostic factors in BC patients treated with nCT.

     

Ovarian suppression in combination endocrine adjuvant therapy in premenopausal women with early breast cancer

Purpose

The benefits of adding ovarian suppression to either tamoxifen or aromatase inhibitors as adjuvant breast cancer therapy in premenopausal women are controversial. Therefore, we performed a systematic literature review and meta-analysis of relevant randomized trials.

Methods

We identified and combined four qualifying trials reporting disease-free survival (DFS) and overall survival (OS) using meta-analysis.

Results

Combining ABCSG-12, SOFT, and TEXT studies, there were 65 fewer DFS events (HR 0.89, 95% CI 0.57–1.39) but 30 more deaths for ovarian suppression plus aromatase inhibitor compared to ovarian suppression plus tamoxifen (HR 1.31, 95% CI 0.93–1.84, P = 0.12, τ = 0.03, heterogeneity, P = 0.18). DFS and OS were more concordant for combined SOFT and E-3193 findings; for ovarian suppression plus tamoxifen compared to tamoxifen alone, there were 24 fewer DFS events (HR 0.83, 95% CI 0.67–1.07, P = 0.09, τ ² = 0) and 14 fewer deaths (HR 0.76, 95% CI 0.53–1.07). The SOFT Estrogen Substudy demonstrated inconsistent estrogen suppression with combined ovarian suppression and aromatase inhibitor.

Conclusion

Given the discordance between DFS and OS and inconsistent estrogen suppression with ovarian suppression plus aromatase inhibitor, adding aromatase inhibitor to ovarian suppression as adjuvant therapy in premenopausal women is premature.

     

Factors affecting the recurrence and survival of hepatocellular carcinoma after hepatectomy: a retrospective study of 601 Chinese patients

Objective

Indications for resection of hepatocellular carcinoma (HCC) remain controversial. This study aimed to identify prognostic factors that affect overall survival (OS) and disease-free survival (DFS) in patients with HCC after hepatectomy.

Methods

From 2004 to 2010, 601 patients with HCC who underwent resection were enrolled. Factors stratified into the host, biochemical, surgical treatment and tumor-related features in terms of recurrence and overall survival were analyzed. Prognostic factors were evaluated by univariate and multivariate analyses, with Kaplan–Meier survival analyses and Cox proportional hazard model.

Results

The overall survival rates of 1-, 3- and 5- year were 79, 62, and 54 %, and the corresponding DFS rates were 51, 38 and 31 %, respectively. In a multivariate analysis, Child–Pugh, serum AFP level, ALT level, time for hepatic resection, tumor differentiation, maximum size of tumors, local necrosis, portal vein tumor thrombus, and TNM Stage were correlated significantly with patients’ OS. Gender (P = 0.046), cigarette smoking (P = 0.007), serum AFP level (P = 0.001), GGT level (P = 0.002), maximum size of tumors (P = 0.009), liver cirrhosis (P = 0.025), portal vein tumor thrombus (P = 0.022), microvascular tumor thrombus (P = 0.007) and TNM Stage (P = 0.001) were significantly affected DFS.

Conclusion

Preoperative AFP level, maximum size of tumors, portal vein tumor thrombus and TNM Stage were revealed as important prognostic factors for OS and DFS through follow-up of a relatively large cohort of Chinese HCC patients.

     

The influences of peritumoral lymphatic invasion and vascular invasion on the survival and recurrence according to the molecular subtypes of breast cancer

Purpose

We aimed to compare the influences of lymphatic invasion (LI) and vascular invasion (VI) on survival and recurrence according to the molecular subtypes of breast cancer.

Methods

We retrospectively analyzed data on 820 breast cancer patients and assessed overall survival (OS) and disease-free survival (DFS) according to LI and VI using the Kaplan–Meier estimator and the Cox proportional hazards model.

Results

Both positive LI and positive VI showed inferior OS and DFS compared with negative LI and negative VI (all p < 0.001). Both positive LI and positive VI showed higher local, regional, and distant recurrence rates (p = 0.002 for regional recurrence of VI, p < 0.001 for all the others). Although LI was a significant independent predictor of OS (hazard ratio [HR] 1.927; 95% confidence interval [CI] 1.046–3.553) and DFS (HR 1.815; 95% CI 1.063–3.096), VI was not in the multivariate analyses. Regarding OS, both positive LI and positive VI showed worse survival rates in the luminal A (p = 0.016 and p = 0.024, respectively) and triple negative subtypes (both p < 0.001). Regarding DFS, LI was a significant prognosticator in the luminal A and triple negative (both p < 0.001) subtypes. VI was a significant prognosticator across all molecular subtypes, although the prognostic impact was most prominent in the luminal A subtype (p < 0.001).

Conclusions

Both LI and VI were significant, unfavorable prognostic factors of OS and DFS, especially in the luminal A and triple negative breast cancer subtypes. Although LI was a significant independent predictor of OS and DFS, VI was not after the multivariate analyses.

     

Preoperative platelet–lymphocyte ratio is an independent prognostic marker and superior to carcinoembryonic antigen in colorectal peritoneal carcinomatosis patients undergoing cytoreductive surgery and hyperthermic intraperitoneal chemotherapy

Objective

The aim of this study was to examine the prognostic significance of preoperative inflammatory-based indices, platelet–lymphocyte ratio (PLR), neutrophil–lymphocyte ratio (NLR), and carcinoembryonic antigen (CEA) in predicting overall survival (OS) in patients with colorectal peritoneal carcinomatosis (CPC) treated with cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

Methods

Sixty patients with pathologically confirmed CPC treated with CRS and HIPEC between 2003 and 2015 were included. Levels of preoperative PLR, NLR, and CEA were recorded. Univariate and multivariate analyses were conducted to identify prognostic factors associated with OS.

Results

Median OS was 36 months (95% CI, 26.6–45.4) and 5-year OS was 40.5% (95% CI, 27.3–51.6%). Preoperative PLR (p = 0.034) and CEA (p = 0.036) were found to be significant prognostic markers of OS, whereas NLR did not affect OS. PLR remained significant on multivariate analysis (hazard ratio, 1.035; 95% CI, 1.027–1.043; p < 0.001).

Conclusion

Our study indicates that preoperative PLR may be used as a prognostic marker in CPC patients undergoing CRS and HIPEC and could be useful in the preoperative setting when selecting patients for surgery. The subset of patients with PLR > 300 have a median OS of 5 months (95% CI, 0–24.6 months), indicating that CRS and HIPEC may not be superior to systemic chemotherapy in this subset of patients.

     

Neutrophil to lymphocyte ratio associated with prognosis of lung cancer

Purpose

Many studies recently focus on complicated and expensive genomic tests, but the prognostic values of biochemical markers which are easily obtained in clinics are largely overlooked and without further exploration. This study assesses the association of neutrophil–lymphocyte-ratio (NLR) with prognosis of lung cancer patients.

Methods

In 1032 patients with histologically confirmed lung cancer, the association of pretreatment NLR values with overall survival (OS) was evaluated using a Cox proportional hazards model and the temporal relationship of longitudinal NLR was assessed using a mixed effects model.

Results

Compared to the patients with a low pretreatment NLR value, those with elevated NLR exhibited a statistically significant worse OS with a hazard ratio (HR) of 1.50 (P < 0.0001) after adjusting for age, gender, race, smoking status, drinking status, tumor stage, tumor grade, histology, and treatments. A significant trend of increasing HRs along with increasing NLR values was observed. The increased risk of death conferred by pretreatment NLR values reached a peak level around 2 years after diagnosis. Moreover, in longitudinal analysis, we observed a trend of dramatically increased NLR values in patients who died during follow-up, but stable NLR values in those who were still alive, with a significant interaction of death–alive status with follow-up time (P < 0.0001).

Conclusions

Elevated NLR is a potential biomarker to identify lung cancer patients with poor prognosis and should be validated in a future clinical trial.

     

Prognostic implication of the primary tumor location in early-stage breast cancer: focus on lower inner zone

Background

The aim of this study was to investigate the prognostic significance of tumor location of lower inner zone (LIZ) on the survival of patients with early-stage breast cancer.

Methods

We retrospectively identified 961 breast cancer patients from Jan 2000 to Apr 2016 from hospital database. We evaluated overall survival (OS) and disease-free survival (DFS) in patients with tumors in and outside LIZ. Subgroup analyses were performed according to clinicopathological characteristics and treatment strategies.

Results

A total of 838 cases were finally included. Patients with tumor location of LIZ showed significantly lower survival rates than tumors in other sites in terms of DFS (p = 0.028) but not OS (p = 0.106). When stratified into subgroups, tumors in LIZ retained a significant worse prognosis in DFS in patients with HER-2-negative, high ki-67 expression breast cancers, those who received neoadjuvant chemotherapy, axillary nodal negative patients, and patients with lymphovascular invasion. Univariate and multivariate analyses suggested that tumor location of LIZ was an independent prognostic factor for DFS (p = 0.022).

Conclusions

Our results suggested that tumor location of LIZ was an independent adverse prognostic factor for DFS in patients with early-stage breast cancer. Multicenter studies with larger sample size are needed to confirm the conclusion and anatomical experiments are desired to elaborate the mechanism.

     

Individualized induction chemotherapy by pre-treatment plasma Epstein-Barr viral DNA in advanced nasopharyngeal carcinoma

Background

The role of pretreatment Epstein-Barr virus DNA (pre-DNA) for individualized induction chemotherapy (IC) in locoregionally advanced nasopharyngeal carcinoma (LA-NPC) still remains unknown. We aimed to address this clinical issue.

Methods

In total, data on 6218 patient with newly diagnosed LA-NPC receiving concurrent chemoradiotherapy (CCRT) with or without IC were retrospectively reviewed. Receiver operating characteristics (ROC) curve was adopted to calculate the cut-off value of pre-DNA based on disease-free survival (DFS). Propensity score matching (PSM) method was adopted to balance prognostic factors and match patients. Survival outcomes between IC?+?CCRT and CCRT groups were compared.

Results

Among the original cohort, no survival difference between IC?+?CCRT and CCRT groups was found. The cut-off value of pre-DNA was 4650 copies/ml (area under curve [AUC], 0.620; sensitivity, 0.6224; specificity, 0.5673). For patients with Pre-DNA?≤?4650 copies/ml, the IC?+?CCRT and CCRT groups also achieved comparable survival outcomes (P?>?0.05 for all rates). However, IC?+?CCRT was associated with significantly improved 3-year DFS (78.6% vs. 74.8%, P?=?0.03), overall survival (OS; 91.4% vs. 87.5%, P?=?0.002) and distant metastasis-free survival (DMFS; 86.0% vs. 82.2%, P?=?0.036) for patient with pre-DNA?>?4650 copies/ml. Multivariate analysis also confirm that IC?+?CCRT was an independent prognostic factor for DFS (HR, 0.817; 95% CI, 0.683–0.977; P?=?0.027), OS (HR, 0.675; 95% CI, 0.537–0.848; P?=?0.001) and DMFS (HR, 0.782; 95% CI, 0.626–0.976; P?=?0.03).

Conclusions

Pre-DNA may be a feasible and powerful consideration for individualized IC apart from other baseline clinical characteristics in LA-NPC.

     

Retrospective review of genomic testing in breast cancer: Does it improve outcome?

Purpose

Angiogenesis is one of the hallmarks of cancer and is essential for cancer progression and metastasis. However, clinical trials with vascular endothelial growth factor (VEGF) pathway inhibitors have failed to show overall survival benefit in breast cancer. Targeted therapy against the angiopoietin pathway, a downstream angiogenesis cascade, could be effective in breast cancer. This study investigates the association of angiopoietin pathway gene expression with breast cancer survival using a “big data” approach employing RNA sequencing data from The Cancer Genome Atlas (TCGA).

Methods

A total of 888 patients with adequate gene expression, disease-free survival (DFS), and overall survival (OS) data were selected for analysis. DFS and OS were calculated for patients with high and low expression of angiopoietin and VEGF pathway genes using TCGA data. Gene-specific thresholds to dichotomize patients into high and low expression were determined and survival plots were generated.

Results

The TCGA cohort was representative of national breast cancer patients with respect to stage, pathology, and survival. High Ang2 gene expression was associated with not only decreased DFS (p = 0.05), but also decreased OS (p < 0.05). High co-expression of Ang2 and its receptor Tie2 was associated with both decreased DFS and OS (p < 0.05). There was strong correlation between angiopoietin and VEGF pathway genes. While high expression of VEGFA alone was not associated with survival, high co-expression with Ang2 was associated with decreased OS.

Conclusions

This study validates TCGA as a representative database providing genomic data and survival outcomes in breast cancer. Our TCGA data support the angiopoietin pathway as a key mediator in the pathologic angiogenic switch in breast cancer.

     

Carcinosarcoma of the ovary compared to ovarian high-grade serous carcinoma: impact of optimal cytoreduction and standard adjuvant treatment

Objective

The purpose of this retrospective study was to compare the prognoses of women with ovarian carcinosarcoma (OCS) who had optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy to those of women with ovarian high-grade serous carcinoma (HGSC) treated in the same manner.

Methods

A multicenter, retrospective department database review was performed to identify patients with OCS at eight gynecologic oncology centers in Turkey. A total of 54 women with OCS who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy between 1999 and 2017 were included in this case–control study. Each case was matched to two women with ovarian HGSC who had undergone optimal cytoreductive surgery followed by platinum plus taxane combination chemotherapy. The Kaplan–Meier method was used to generate survival data. Factors predictive of outcome were analysed using Cox proportional hazards models.

Results

Median disease-free survival (DFS) was 29 months [95% confidence interval (CI) 0–59, standard error (SE) 15.35] versus 27 months (95% CI 22.6–31.3, SE 2.22; p = 0.765) and median overall survival (OS) was 62 versus 82 months (p = 0.53) for cases and controls, respectively. For the entire cohort, the presence of ascites [hazard ratio (HR) 2.32; 95% CI 1.02–5.25, p = 0.04] and platinum resistance [HR 5.05; 95% CI 2.32–11, p < 0.001] were found to be independent risk factors for decreased OS.

Conclusion

DFS and OS rates of patients with OCS and HGSC seem to be similar whenever optimal cytoreduction is achieved and followed by platinum plus taxane combination chemotherapy.

     

Surgical Management of Metastatic Colorectal Cancer: A Single-Centre Experience on Oncological Outcomes of Pulmonary Resection vs Cytoreductive Surgery and HIPEC

Purpose

Metastasectomy is accepted as standard of care for selected patients with colorectal pulmonary metastases (CLM); however, the role of cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC) for colorectal peritoneal metastases (CPM) is not universally accepted. We aim to compare oncological outcomes of patients with CLM and CPM after pulmonary resection and CRS-HIPEC, respectively, by comparing overall survival (OS) and disease-free survival (DFS).

Methods

A retrospective review of 49 CLM patients who underwent pulmonary resection, and 52 CPM patients who underwent CRS-HIPEC in a single institution from January 2003 to March 2015, was performed.

Results

The 5-year OS for CLM patients and CPM patients were 59.6 and 40.5%, respectively (p = 0.100), while the 5-year DFS were 24.0 and 14.2%, respectively (p = 0.173). CPM patients had longer median operative time (8.38 vs. 1.75 h, p < 0.001), median hospital stay (13 vs. 5 days, p < 0.001), a higher rate of intensive care unit (ICU) admissions (67.3 vs. 8.2%, p < 0.001), and a higher rate of high-grade complications (17.3 vs. 4.1%, p < 0.001). Multivariate analysis demonstrated that recurrent lung metastasis after metastasectomy was an independent prognostic factor for OS of CLM patients (OR = 0.045, 95%, CL 0.003–0.622, p = 0.021). There were no independent prognostic factors for OS in CPM patients by multivariate analysis. There were no independent prognostic factors for DFS in CLM patients by multivariate analysis, but peritoneal cancer index score, bladder involvement, and higher nodal stage at presentation of the initial malignancy were independent prognostic factors for DFS in CPM patients.

Conclusions

OS and DFS for CPM patients after CRS and HIPEC are comparable to CLM patients after lung resection, although morbidity appears higher. The prognostic factors affecting survival after surgery are different between CPM and CLM patients and must be considered when selecting patients for metastasectomy.

     

Total iron-binding capacity is a novel prognostic marker after curative gastrectomy for gastric cancer

Background

Patients with gastric cancer (GC) are affected by changes in iron status. Before surgery, GC patients are likely to have iron-deficiency anemia; and after gastrectomy, patients suffer from low nutritional status and low iron. This study investigated preoperative iron status associated with prognosis after curative gastrectomy for gastric cancer.

Methods

We evaluated preoperative serum hemoglobin (Hgb), Fe and total iron-binding capacity (TIBC) in 298 patients who underwent curative gastrectomy for GC without preoperative chemotherapy, and analyzed these factors’ associations with prognosis after surgery.

Results

Of the 298 patients, 129 (43.2%) had low Hgb levels, and 33 (11.1%) had low TIBC (<?260 µg/dl) that was not associated with Hgb or Fe level. Patients with low TIBC were significantly associated with older age (≥?65 years old; P?=?0.0085), low albumin (<?3.9 g/dl; P?=?0.0388) and high CRP (≥?0.15 mg/dl; P?=?0.0018) in multivariate analysis. Low Fe (<?60 µg/dl) was not associated with disease-free survival (DFS) or overall survival (OS); however, low Fe was associated with longer cancer-specific survival in Stage III GC patients (P?=?0.0333). Both low Hgb and low TIBC were significantly associated with shorter DFS (Hgb: P?=?0.0433; TIBC: P?<?0.0001) and shorter OS (Hgb: P?=?0.0352; TIBC: P?<?0.0001). Low TIBC were significantly associated with shorter DFS (HR 2.167, 95% CI 1.231–3.639, P?=?0.0086) and shorter OS (HR 2.065, 95% CI 1.144–3.570, P?=?0.0173) in multivariate Cox hazard regression analysis.

Conclusions

Preoperative serum TIBC level of GC patients who undergo curative gastrectomy is a novel prognostic marker in univariate and multivariate analyses.

     

Polymorphisms of <Emphasis Type="Italic">MTHFR</Emphasis> C677T and A1298C associated with survival in patients with colorectal cancer treated with 5-fluorouracil-based chemotherapy

Background

This study examined the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and survival of patients with colorectal cancer (CRC) treated with 5-fluorouracil (5-FU)-based chemotherapy in Taiwan.

Methods

We genotyped MTHFR polymorphisms C677T (rs1801133) and A1298C (rs1801131) for 498 CRC patients treated with 5-FU-based chemotherapy after receiving surgery. Survival analyses on MTHFR polymorphisms were performed using log-rank test and Kaplan–Meier curve. Cox proportional hazards models were used to calculate the hazard ratios (HRs) and 95% confidence intervals (CIs) for the association between MTHFR genotypes and survival.

Results

Overall survival (OS) was significantly longer in CRC patients with MTHFR 677 CT+TT genotypes compared with those with 677 CC genotype (HR 0.77; 95% CI 0.60–0.98). Although the MTHFR A1298C polymorphism was not associated with OS in CRC, this polymorphism was associated with significantly shorter OS in rectal cancer. Among rectal cancer patients, OS was shorter for patients with AC+CC genotypes than for those with the AA genotype (HR 1.95; 95% CI 1.35–2.83). In haplotype analysis, better OS was found for colon cancer patients carrying the MTHFR 677T-1298A haplotype (HR 0.73; 95% CI 0.55–0.97), but worse survival was linked to rectal cancer patients carrying the MTHFR 677C-1298C haplotype (HR 1.53; 95% CI 1.08–2.18).

Conclusions

Our findings suggest that MTHFR genotypes provide prognostic information for CRC patients treated with 5-FU-based chemotherapy.

     

Does the TNM classification of solitary internal mammary lymph node metastases in breast cancer still apply?

Purpose

TNM classification of solitary internal mammary lymph node metastases (IMLNMs) in breast cancer varies depending on their method of detection: sentinel lymph node biopsy (pN1b) or clinical examination including radiological and/or physical examination (pN2b). This study aimed to evaluate whether there is a difference in prognosis between both groups.

Methods

Data of all patients diagnosed with primary invasive epithelial breast cancer between 2005 and 2008 were obtained from the Netherlands Cancer Registry. Patients with IMLNMs were divided in groups according to their pN1b and pN2b status. The main outcome measures disease-free survival (DFS) after 5 years and overall survival (OS) after 8 years were analyzed using Kaplan–Meier survival analysis. Cox regression analysis was used to determine independent predictors for DFS and OS.

Results

A total of 73 patients with pN1b status and 28 patients with pN2b status were included. DFS rate was 74.1% in the pN1b group compared to 85.0% in the pN2b group (p = 0.211). Regarding OS, 20.5% (pN1b) and 25.0% (pN2b) of the patients deceased within 8 years of follow-up (p = 0.589). In multivariable cox regression analysis, nodal status was not statistically significant for DFS (HR 0.29 [95% CI 0.04–2.33], p = 0.244) or OS (HR 1.04 [95% CI 0.37–2.89], p = 0.947).

Conclusions

Although the TNM classification considers pN1b and pN2b to be distinct prognostic entities, we did not observe any prognostic differences between these groups. Therefore, solitary IMLNMs may be regarded as a single category in the future and revision of TNM classification should be considered.

     

<Emphasis Type="Italic">BRCA1</Emphasis>-like profile is not significantly associated with survival benefit of non-myeloablative intensified chemotherapy in the GAIN randomized controlled trial

Purpose

The BRCA1-like profile identifies tumors with a defect in homologous recombination due to inactivation of BRCA1. This profile has been shown to predict which stage III breast cancer patients benefit from myeloablative, DNA double-strand-break-inducing chemotherapy. We tested the predictive potential of the BRCA1-like profile for adjuvant non-myeloablative, intensified dose-dense chemotherapy in the GAIN trial.

Methods

Lymph node positive breast cancer patients were randomized to 3 × 3 dose-dense cycles of intensified epirubicin, paclitaxel, and cyclophosphamide (ETC) or 4 cycles concurrent epirubicin and cyclophosphamide followed by 10 cycles of weekly paclitaxel combined with 4 cycles capecitabine (EC-TX). Only triple negative breast cancer patients (TNBC) for whom tissue was available were included in these planned analyses. BRCA1-like or non-BRCA1-like copy number profiles were derived from low coverage sequencing data.

Results

119 out of 163 TNBC patients (73%) had a BRCA1-like profile. After median follow-up of 83 months, disease free survival (DFS) was not significantly different between BRCA1-like and non-BRCA1-like patients [adjusted hazard ratio (adj.HR) 1.02; 95% confidence interval (CI) 0.55–1.86], neither was overall survival (OS; adj.HR 1.26; 95% CI 0.58–2.71). When split by BRCA1-like status, DFS and OS were not significantly different between treatments. However, EC-TX seemed to result in a trend to an improvement in DFS in patients with a BRCA1-like tumor, while the reverse accounted for ETC treatment in patients with a non-BRCA1-like tumor (p for interaction = 0.094).

Conclusions

The BRCA1-like profile is not associated with survival benefit for a non-myeloablative, intensified regimen in this study population. Considering the limited cohort size, capecitabine might have additional benefit for TNBC patients.

     

Can tumor regression grade influence survival outcome in ypT3 rectal cancer?

Purpose

Locally advanced rectal cancer (LARC) patients achieving ypT3 status following neoadjuvant chemoradiation are considered to have poor response with minimal downstaging. However, residual cancer cell amounts vary in the subserosa/perirectal fat. Tumor regression grading (TRG) is an evaluation method based on the proportion of fibrosis and residual cancer cells. The aim of this study is to assess the influence of TRG in ypT3 rectal cancer patients who received neoadjuvant chemoradiation.

Methods

We retrospectively reviewed 325 LARC patients who received neoadjuvant chemoradiation and surgery. TRG scores were recorded by two independent pathologists. Among these patients, 143 were staged as ypT3. We analyzed TRG and other clinicopathological factors and their relationship with survival outcome including overall survival (OS) and disease-free survival (DFS).

Results

Among 143 ypT3 patients, 44 (30.8 %) were TRG1, 84 (58.7 %) were TRG2 and 15 (10.5 %) were TRG3. Seventy-nine (55.3 %) of these patients had metastatic lymph nodes. In univariate analysis, TRG was not associated with DFS (TRG2 vs TRG1, P = 0.852; TRG3 vs TRG1, P = 0.593) or OS (TRG2 vs TRG1, P = 0.977; TRG3 vs TRG1, P = 0.665). Palliative surgery (HR 3.845; 95 % CI 1.670–8.857; P = 0.002) and metastatic lymph nodes after surgery (HR 5.894; 95 % CI 1.142–3.48; P = 0.015) were significantly associated with decreased DFS, while palliative surgery was the only factor associated with worse OS (HR 6.011; 95 % CI 2.150–16.810; P = 0.001). Palliative surgery (HR 3.923; 95 % CI 1.696–9.073; P = 0.001) and metastatic lymph nodes (HR 2.011; 95 % CI 1.152–3.512; P = 0.014) also showed prognostic significance for DFS in multivariate analysis.

Conclusions

Residual cancer cells evaluated by TRG score after neoadjuvant chemoradiation do not influence survival outcome in ypT3 rectal cancer patients. However, lymph node status is a significant prognostic factor in ypT3 patients.