Do the derived neutrophil to lymphocyte ratio and the neutrophil to lymphocyte ratio predict prognosis in breast cancer?

BACKGROUND: The neutrophil-to-lymphocyte ratio (NLR) is a strong predictor of mortality in patients with cancer. Similarly, a study in a large series has shown that the newly defined derived NLR (dNLR; neutrophil/leukocyte-lymphocyte ratio) also has prognostic value. The present study retrospectively evaluates the prognostic significance of NLR and dNLR in breast cancer. METHODS: Hematological parameters and clinicopathological data during diagnosis were retrospectively recorded for 1,527 patients diagnosed with breast cancer at Izmir Katip Celebi University Ataturk Research and Training Hospital from January 2006 to December 2011. The cut-off values were determined by calculating the NLR and dNLR of the patients. RESULTS: The cut-off values were determined as 4 and 2 for NLR and dNLR, respectively. The association between NLR and dNLR assessed by Spearman's rank correlation analysis was 0.935 (P < 0.001). There was a significant difference regarding disease free survival (DFS) and overall survival (OS) in patients with NLR <4 and NLR ≥4 (respectively, P < 0.00, P < 0.001). Similarly, there was a significant difference regarding DFS and OS in patients with dNLR <2 and dNLR ≥2 (respectively, P < 0.001, P < 0.001). Furthermore, NLR and dNLR demonstrated a significant association with the American Joint Committee on Cancer (AJCC) staging (P < 0.001). Assessment using the Cox proportional multivariate model showed that high NLR, pN, pT, luminal A-like, luminal B-like (HER2 positive), basal-like, and AJCC staging are independent prognostic factors. DISCUSSION: NLR was shown to be better than dNLR in terms of predicting prognosis in patients with breast cancer. However, large prospective studies are required to further demonstrate the prognostic significance of these two values.

The impact of cell proliferation markers and p53 mutation status on prognosis of non-metastatic colon cancer.

BACKGROUND AND OBJECTIVES: We aimed to evaluate the prognostic value of cell cycle proteins and p53 together with clinicopathologic features in non-metastatic resected colon cancer. METHODS: One hundred nine patients who were diagnosed with resected colon cancer between 2006 and 2011 were analyzed retrospectively. Immunohistochemical staining analyses were used to evaluate the expression of cyclins D1 and A, p53 and Ki-67 in tumor tissue. RESULTS: High cyclin D1 and cyclin A expression was more common in stage II than stage III tumors. Disease recurrence was more frequent in tumors with low cyclin D1 expression (P = 0.05). No significant association was observed between p53, Ki-67 or cyclin A expression and the risk of relapse and/or death. Multivariate analysis showed that the strongest predictor for a shorter disease-free survival period was extracapsular nodal invasion (ECNI). CONCLUSIONS: We were not able to establish a strong association between patient prognosis and cyclins D1 and A, p53 or Ki-67 expression. However, a negative correlation between cyclin D1 and cyclin A expression and disease stage as well as more frequent relapses in patients with low expression of cyclin D1 suggested that cyclins may be predictive for early relapse in non-metastatic colon cancer.

Prognostic evaluation of breast cancer patients with evident bone marrow metastasis.

In this study, we aimed to evaluate the clinicopathologic characteristics and prognosis of breast cancer (BC) patients with symptomatic bone marrow metastasis (BMM). Fifty-four BC patients, including patients with and without BMM, were evaluated retrospectively. In particular, the clinicopathologic features and survival of the patients with BMM (n = 27) were assessed and compared with the patients without BMM. All of the patients with BMM also had osseous metastases, and bone was the first site for distant recurrence in the majority of patients in the study group. Anemia was the most frequent symptom at presentation. The median time to BMM was 36.1 months (range 1.6-70.5 months, 95% CI). HER2(+) patients developed BMM earlier than HER2(-) patients (3.2 versus 38.3 months, 95% CI; p = 0.05). Patients with advanced disease at the time of initial BC diagnosis developed BMM earlier than patients with early disease (p = 0.04). Time to development of BMM was significantly shorter in tumors with perinodal infiltration (p = 0.001) and multicentric focus (p = 0.025). Median survival time after the diagnosis of apparent BMM was 6.43 months. Survival after BMM diagnosis in patients with grade III tumors was significantly shorter than in patients with grade I-II tumors (1.43 versus 5.36 months, 95% CI; p < 0.001). Systemic therapy after BMM diagnosis significantly prolonged survival (17.3 versus 0.93 months, 95% CI; p < 0.001). Hormone receptor-positive, high-grade, advanced-stage tumors at the time of initial BC diagnosis were more common in patients with BMM. Invasive lobular histology was also more frequent in patients with BMM. In conclusion, the presence of hormone receptor-positive, multicentric, grade III, advanced-stage tumors may be important risk factors for the development of evident BMM in BC patients. Systemic single-agent chemotherapy can prolong survival in these patients. However, multicenter analyses are required to verify these findings.

Enhanced cytotoxicity and apoptosis by thymoquinone in combination with zoledronic acid in hormone- and drug-resistant prostate cancer cell lines.

PURPOSE: Thymoquinone (TQ), an active ingredient of black seed oil (Nigella Sativa), has been shown to possess cytotoxic activity against a variety of cancer cell lines. Our purpose was to investigate if the cytotoxic and apoptotic effect of zoledronic acid (ZA) can be enhanced by the addition of the TQ in hormone- and drug-refractory prostate cancer cells PC-3 and DU-145. METHODS: XTT cell proliferation assay was used to assess cytotoxicity; DNA fragmentation and caspase 3/7 activity were also measured. RESULTS: The combination of TQ and ZA resulted in a significant synergistic cytotoxic activity and DNA fragmentation when compared to any single agent alone, in a dose- and time-dependent manner. In addition, TQ and ZA combination increased the caspase 3/7 activity in PC-3 cell line, while this activity could not be demonstrated in DU-145 cell line. CONCLUSION: TQ and ZA had minimal hematological and non-hematological toxicity profile compared to cytotoxic agents. So, this combination may be an alternative approach for patients who are unable to be treated by conventional treatments because of poor performance status.

Capecitabine-related increased mean corpuscular volume of red blood cell may be a predictive marker of treatment response and survival in patients with metastatic colorectal cancer.

PURPOSE: Erythrocyte mean corpuscular volume (MCV) increase has been described in patients treated with capecitabine. In this study, we sought to evaluate the potential association of the erythrocyte MCV increase with tumor response and survival in patients with metastatic colorectal cancer (mCRC) treated with capecitabine. METHODS: A retrospective review of 131 patients with mCRC who were treated with capecitabine for at least 3 months at the Izmir Training and Research Hospital was undertaken. Complete blood count (CBC) including red blood cell indices were recorded at baseline and after 9 weeks from capecitabine treatment. RESULTS: The mean patient age was 57.9 years (range 28- 82). In patients treated with capecitabine, MCV increased significantly at 9 weeks compared with baseline (p=0.000). Median ΔMCV [(post-treatment MCV values) - (baseline MCV values)] level was 9.3 fL. Patients were grouped according to ΔMCV into two groups (> 9.3 or ≥ 9.3) in order to carry out survival analysis and correlation with tumor response. ΔMCV was >9.3 in 65 patients and ≤9.3 in 66 patients. Fifty-six of the 65 patients with ΔMCV levels >9.3 and 37 of the 66 patients with ΔMCV levels ≤9.3 had a clinical benefit (complete response + partial response + stable disease) from capecitabine treatment (p=0.000). The difference between progression-free survival (PFS) and overall survival (OS) of the patients who had ΔMCV>9.3 and those who had ≤9.3 was statistically significant (9.48 and 6.94 months, p=0.001 respectively; and 17.5 and 13.6 months respectively, p=0.018). Univariate analysis suggested that a favorable prognosis for OS and PFS was associated with MCV increase (p=0.000). In multivariate analysis, MCV increase was independently associated with favorable survival outcomes. CONCLUSIONS: Erythrocyte MCV increase may be used as a predictive marker for treatment response, PFS and OS in patients with mCRC treated with capecitabine.

Intramammary lymph node metastasis in a patient with ovarian carcinoma and a brief review of the literature.

Metastasis from serous carcinoma of the ovary usually occurs in the subdiaphragmatic region. Metastasis to the breast and/or axillary-intramammary lymph node is very rare. It usually occurs in advanced disease, and it is important to distinguish a primary breast cancer from an ovarian cancer metastasis since the management of these two entities is totally different. Here we present a patient with metastasis to the breast and intramammary lymph nodes from ovarian serous carcinoma 25 months after diagnosis.

Cutaneous and subcutaneous metastases from bladder carcinoma.

Cutaneous metastases of bladder carcinoma are very rare. The rate of cutaneous metastasis in urologic malignancies is 1.3% and this rate was found to be 0.84% for bladder carcinomas. Cutaneous metastasis of bladder carcinoma can be confused with cellulitis. This case report presents a 60-year-old patient operated on for bladder carcinoma and undergoing treatment for cellulitis because of erythematous lesions appearing in the suprapubic region in the early postoperative period. As there was no response to antibiotic treatment, skin biopsy was performed and cutaneous metastasis was diagnosed. Subsequently, chemotherapy with carboplatin and gemcitabine was started. The prognosis of bladder carcinoma with cutaneous metastasis has been reported to be poor.

Overcoming drug resistance in hormone- and drug-refractory prostate cancer cell line, PC-3 by docetaxel and gossypol combination.

Drug resistance is a significant challenge of daily oncology practice. Docetaxel and gossypol both have antitumoral activity in hormone-refractory prostate cancer (HRPC). Our results revealed that docetaxel and gossypol were synergistically cytotoxic and apoptotic in PC-3 cells in a dose- and time-dependent manner. We further investigated the expression profiles of genes involved in drug resistance and metabolism with a Human Cancer Drug Resistance and Metabolism PCR Array (SuperArray). Six of the 84 genes that are known to regulate drug resistance, metabolism, cell cycle, DNA repair and oncogenesis were downregulated >or=3-fold change by the combination treatment. These results may be important in devising mechanism-based and targeted therapeutic strategies for prostate cancer, especially in devising combination therapy for drug resistant prostate cancers.

Regulation of growth factors in hormone- and drug-resistant prostate cancer cells by synergistic combination of docetaxel and octreotide.

OBJECTIVE To evaluate the effects of combined treatment with docetaxel and octreotide, a somatostatin analogue, on human hormone- and drug-refractory prostate cancer cell lines, PC-3 and DU-145, and on some growth factors related to tumour growth and angiogenesis in prostate cancer. MATERIALS AND METHODS A cell proliferation assay was used to assess the cytotoxicity of the drugs. To verify apoptosis, both DNA fragmentation (by enzyme-linked immunosorbent assay) and caspase 3/7 activity were measured. We also investigated the effect of combined docetaxel and octreotide on growth factors secreted from prostate cancer cells using a human growth factor antibody array. RESULTS The combination of docetaxel and octreotide resulted in significant synergistic cytotoxic activity and apoptosis, which was dose- and time-dependent. The combined treatment also resulted in significantly less secretion of stem cell factor and platelet-derived growth factor-AB in PC-3 cells, and transforming growth factor-beta and basic fibroblast growth factor in DU-145 cells, than in untreated controls. CONCLUSION Octreotide, a somatostatin analogue, combined with docetaxel might provide a rationale treatment option for hormone-refractory prostate cancer cells, not only by direct inhibition of cell proliferation but also by inhibiting the secretion of growth factors.

Cisplatin plus gemcitabine chemotherapy in taxane/anthracycline-resistant metastatic breast cancer.

BACKGROUND: The most commonly used chemotherapeutic regimens in the treatment of metastatic breast cancer (MBC) include anthracyclines and taxanes. In our study, we investigated the efficacy and tolerability of cisplatin plus gemcitabine combination chemotherapy regimen in patients with MBC, who exhibited disease progression after anthracycline- and taxane-based chemotherapy. METHODS: Thirty-three patients with taxane/anthracycline-resistant MBC have been treated with gemcitabine 1,000 mg/m(2) intravenously and cisplatin 30 mg/m(2) intravenously on days 1 and 8 of a 3-week treatment cycle. RESULTS: Thirty-one patients were assessable for response. One of the 31 patients (3.2%) showed complete response, while 7 patients (22.6%) showed partial response; the objective response rate was 25.8%. Stable and progressive disease was observed in 6 (19.4%) and 17 patients (54.8%), respectively. The median time to progression was 4 months (95% CI 2.15-5.85). The median survival time of all patients was 9.5 months (95% CI 7.86-11.14). CONCLUSION: Gemcitabine and cisplatin combination therapy is moderately active and safe in patients with MBC previously treated with anthracycline and taxanes.

Treatment of metastatic colorectal cancer with or without bevacizumab: can the neutrophil/lymphocyte ratio predict the efficiency of bevacizumab?

BACKGROUND: The purpose of this study was to analyze the predictive value of neutrophil/lymphocyte ratio (NLR) to better clarify which patient groups will benefit the most from particular treatments like bevacizumab. MATERIALS AND METHODS: A total of 245 treatment-naive metastatic colorectal cancern (mCRC) patients were retrospectively enrolled and divided into 2 groups: 145 group A patients were treated with chemotherapy in combination with bevacizumab, and 100 group B patients were treated as above without bevacizumab. RESULTS: Group A patients had better median overall survival (OS) and progression-free survival (PFS) (24.0 and 9.0 months) than group B patients (20 and 6.0 months) (p=0.033; p=0.015). In patients with low NLR, OS and PFS were significantly longer in group A patients (27 vs 18 months, p=0.001; 11 vs 7 months, p=0.017). CONCLUSIONS: We conclude that NLR, a basal cancer related inflammation marker, is associated with the resistance to bevacizumab- based treatments in mCRC patients.

Synchronous appearance of a high-grade neuroendocrine carcinoma of the ampulla vater and sigmoid colon adenocarcinoma.

Neuroendocrine carcinoma is a relatively rare tumor and its coexistence with other primary cancers is very exceptional. We present a case of a 63-year-old woman with biliary obstruction due to a high-grade neuroendocrine carcinoma located in ampulla of Vater who was found to have a synchronous sigmoid colon adenocarcinoma while undergoing staging laparotomy and pancreas head resection. Medical history was significant only for basal cell skin cancer. Immunohistochemical examination revealed the concurrence of histologically proved neuroendocrine carcinoma (chromogranin A, synaptophysin, and CD56 were positive) and Stage II (T3, N0, and M0) according to the TNM staging classification of colorectal cancer. The coexistence of neuroendocrine tumors with either synchronous or metachronous unrelated cancer is increasingly recognized. The patients with neuroendocrine carcinoma should be evaluated for secondary primary malignancies.

Clinicopathologic and demographic evaluation of triple- negative breast cancer patients among a turkish patient population: a single center experience.

BACKGROUND: To evaluate the clinicopathologic and demographic characteristics of triple-negative breast cancer (TNBC) patients and to determine differences from non-triple-negative cases. MATERIALS AND METHODS: A detailed review of the medical records of 882 breast cancer (BC) patients was conducted to obtain information regarding age, menopausal status, height and weight at the time of diagnosis, presence of diabetes or hypertension, and pathologic characteristics of the tumor (tumor size, lymph node status, histologic grade, ER status, PR status, HER2 status, p53 mutation). Body mass index (BMI) was calculated and a value of ≥30 was considered as indicative of obesity. RESULTS: 14.9% (n=132) of the patients had TNBC. There was no difference among the patients in terms of median age, comorbid conditions and menopausal status. The proportion of medullary, tubular and mucinous carcinomas was significantly higher (15.9%) in the triple-negative (TN) group, while invasive lobular histology was more frequent (8.2%) among non-triple negative (NTN) cases (p<0.001). Grade 3 (G3) tumors were more frequent in the triple-negative group (p<0.001). The rate of p53 mutation was 44.3% in TN tumors versus 28.2% in the NTN group (p<0.001). The two groups were similar in terms of LN metastasis. In the NTN group, the rate of patients with BMI ≥30 was 53% among postmenopausal patients, while it was 36% among premenopausal women, and the difference was statistically significant (p<0.001). No significant difference was observed in terms of BMI between postmenopausal and premenopausal patients in the TN group (p=0.08). CONCLUSIONS: TNBC rates and clinicopathologic characteristics of the Turkish patient population were consistent with the data from Europe and America. However, no relationship between obesity and TNBC was observed in our study. The association between TNBC and obesity needs to be evaluated in a larger patient population.

Malignant epithelioid hemangioendothelioma progressing after chemotherapy and Interferon treatment: a case presentation and a brief review of the literature.

Epithelioid hemangioendothelioma is a rare, low-grade malignant vascular tumour. It is frequently seen in the liver, but can occur in the lungs, bones, and other soft tissues. Although survival time might be reasonable in cases that can undergo liver transplantation, there is no consensus on the treatment of metastatic patients. We report a 24-year-old female patient with rapidly progressing malignant epithelioid hemangioendothelioma that presented with acute abdominal distension. The patient was refractory to anthracycline and Interferon treatment and died 6.5 months after the diagnosis.

Cisplatin plus gemcitabine for treatment of breast cancer patients with brain metastases; a preferential option for triple negative patients?

BACKGROUND: To assess the efficacy and tolerability of Cisplatin plus Gemcitabine combination in patients with brain metastases (BM) from breast cancer (BC). MATERIALS AND METHODS: Eighteen BC patients with BM who were treated with Cisplatin plus Gemcitabine regimen between 2003-2011 were evaluated. RESULTS: A median of 6 cycles of this regimen were received, in fifteen patients (83.3%) as first-line chemotherapy, in 2 as second- line and in 1 as third-line after diagnosis of BM. Dose reduction was performed in 11 (61.1%) patients; major reasons were neutropenia and leukopenia. Grade III neutropenia and Grade II trombocytopenia rates were 33.3% and 16.7% respectively. Overall response rate (ORR; complete+partial response rate) was 33.4% (n=6) for the entire study population; triple negative patients achieved an 66.6% ORR while hormone receptor (HR) positive patients had 25% and HER2 positive patients 12.5%. Median progression-free survival was 5.6 months (2.4-8.8 months, 95%CI) and longer in patients with triple negative breast cancer (TNBC) (median 7.4 months, 95%CI, 2.4-12.3 months) than the patients with other subtypes (median 5 months for HER2 positive and 3.6 months for HR positive patients). Median PFS of the patients with TNBC who received this regimen as first-line was 9.2 months (5.2-13.2 months, 95%CI). CONCLUSIONS: Cisplatin plus Gemcitabine may be a treatment option for patients with BM from breast cancer. Longer PFS and higher response rates are results that support the usage of this regimen especially for the triple negative subtype. However, further prospective and randomized trials are clearly required to provide more exact information.

The clinicopathological evaluation of the breast cancer patients with brain metastases: predictors of survival.

We aimed to define the clinicopathologic characteristics of breast cancer (BC) patients with brain metastasis (BM) and to investigate the effect of these parameters on survival. Seventy-nine patients diagnosed with BC and symptomatic BM between 1995 and 2011 were retrospectively evaluated. The relationship between clinicopathological features and outcome was investigated. Triple negative patients had the shortest overall survival (OS) while HR(+)HER2(-) patients had the longest (48.2  vs 88.2 months, 95 % CI; p = 0.33). Multivariate analysis demonstrated that luminal A subtype was the strongest positive predictor of prolonged OS (HR 0.48, 95 % CI 0.28-0.84; p = 0.01), while poor performance status (PS) (ECOG 3-4) at BM was the strongest predictor of shortened OS (HR 1.92, 95 % CI 1.21-3.06; p = 0.006). The patients with early-stage BC at diagnosis had BM later than the advanced-staged patients (47 months for Stage I-II disease, 23.2 months for Stage III-IV disease, 95 % CI; p = 0.002). Median survival after BM was 10.2 months (6.4-14 months, 95 % CI). The patients with liver or skin metastases had significantly shorter survival than the patients with only BM (4.8 vs 17 months, p < 0.001 for liver and 4.8 vs 11.1 months, p = 0.04 for skin). Multivariate analysis demonstrated that regardless of the BC subtype, lack of systemic therapy, and liver involvement were independent factors associated with increased risk of death (HR 4, 95 % CI 1.7-9.1; p = 0.001 and HR 2.2, 95 % CI 1.05-4.9; p = 0.036 respectively). Clinical outcome after BM mostly depends on the ECOG PS and the fact that whether the patient received systemic therapy or not. Systemic therapy prolongs survival especially in HER2 positive patients.

One-day DCF regimen in patients with metastatic gastric cancer.

BACKGROUND: Cytotoxic chemotherapy is the basic treatment for metastatic gastric cancer. The "docetaxel, cisplatin, 5-day infusion of 5-FU (DCF5)" regimen is regarded as an effective therapy. However, the poor toxicity profile of this regimen and administration by 5-day infusion are major drawbacks of this method. METHODS: Patients with measurable metastatic gastric carcinoma, Eastern Cooperative Oncology Group (ECOG) performance status ≤2, normal hematological and renal function, adequate hepatic function, and not pretreated for advanced disease with chemotherapy, received docetaxel on day 1, cisplatin on day 1, and 5-FU peripheral IV on day 1 (DCF1) every 3 weeks. The patients undergoing the DCF1 regimen could not receive the infusion regimen. This was a retrospective study about the use of DCF in 1 day in not previously treated metastatic gastric cancer. RESULTS: In total, 95 patients were treated with a median of 5 cycles per patient. Those not previously treated for advanced disease received docetaxel 75 mg/m² on day 1, cisplatin 75 mg/m² on day 1, and 5-FU peripheral IV 750 mg/m²/day on day 1, plus filgrastim or lenograstim between days 3 and 7. Grade ≥3 toxicities were neutropenia (12%), anemia (11%), thrombocytopenia (3%), fatigue (18%), mucositis (10%), diarrhea (3%), nausea/vomiting (6%), neurological (3%), and palmar-plantar (2%). Two nonfatal febrile neutropenia episodes were recorded. There were no treatment-related deaths. In all patients with measurable disease, we observed an overall response rate of 46% (40 partial responses, 4 complete responses). Thirty-one patients (33%) had stable disease. The median overall survival was 9.0 months (95% CI 7.34-10.6). CONCLUSIONS: Use of the DCF1 regimen in metastatic gastric cancer is feasible, with comparable activity to previous results achieved with epirubicin-based chemotherapy and infusion DCF in terms of overall survival. However, randomized and prospective studies need to be carried out with this regimen.

The effects of hematological parameters and tumor-infiltrating lymphocytes on prognosis in patients with gastric cancer.

BACKGROUND: It is well known that tumor-infiltrating lymphocytes (TIL) and, to a lesser extent, peripheral hematologic parameters from patients with cancer have to effect on prognosis. The aim of this study was to evaluate the effect of hematologic parameters and TIL on prognosis of patients with gastric cancer. METHODS: 236 patients who had diagnosed as gastric adenocarcinoma. All hematologic parameters were noted at the time of diagnosis. The number of lymphocyte aggregates as well as the number of lymphocytes within these agregat was counted.The prognostic significance and correlations of high neutrophil-lymphocyte ratio (NLR) together with TIL, was evaluated by multivaried analysis. RESULTS: The cut-off values of NLR and derived NLR (dNLR) were 3.8 and 2. The NLR was independently associated with survival (P < 0.001). dNLR was not independently associated with overall survival. No significant advantages for overall survival were found for the high TIL (p: 0.372). It was not determined correlation between TIL - NLR and TIL-lymphoid aggregate density (respectivly, P: 0.104; P: 0.246). CONCLUSIONS: The results suggest that the elevated NLR predicts poor overall survival following at the time diagnosis for all stage gastric cancer. dNLR was not independently associated with overall survival. There is insufficient evidence to the assesment of TIL by a nonspesific method. Therefore further studies is required, to confirm our hypothesis in larger patient cohorts.