Microvessel Density and Status of p53 Protein as Potential Prognostic Factors for Adjuvant Anthracycline Chemotherapy in Retrospective Analysis of Early Breast Cancer Patients Group

A considerable subgroup of patients with early breast cancer does not address benefits of anthracycline based chemotherapy. The aim of this retrospective study was to investigate the effect of microvessel density (MVD) and status of p53 protein on 5-year disease free survival (DFS) in the group of breast cancer patients treated with anthracyclines in adjuvant setting. Correlations between MVD, p53 status and other clinicopathological parameters were also assessed. MVD and p53 status were analyzed immunohistochemically in the group of 172 women with breast cancer in clinical stage T1-2, N1-N2, M0. There were 123 tumors (71.5?%) with lower MVD (≤214.8 microvesells/mm(2)) and 49 (28.5?%) with higher MVD (>214.8 microvesells/mm(2)). The proportion of higher MVD tumors significantly increased in N2 (P?=?0.000) and in estrogen (P?=?0.046) or progesterone receptors (P?=?0.029) negative tumors. p53 positivity was indicated in 50 cancers (29.1?%) and was significantly associated with higher grade (P?=?0.000), steroid receptors negativity (P?=?0.000), cytokeratin5/6 positivity (P?=?0.026), topoisomerase IIα overexpression (P?=?0.005) and higher proliferation rate (P?=?0.001). In univariate analysis, higher MVD (P?=?0.016) and p53 negativity (P?=?0.023) were significantly related with longer DFS (median follow-up 36?months). In multivariate Cox regression analysis MVD was independently associated with DFS. These data suggest that higher MVD is favourable prognostic factors for early advanced breast cancer patients after adjuvant anthracycline based chemotherapy.     

Skin Disorders and Primary Tumor Location as Prognostic Factors in Patients with Metastatic Colorectal Cancer Treated with Cetuximab and Chemotherapy

Background: Cetuximab-induced skin disorder is common in colorectal cancer (CRC), and is known to affectprolonged overall survival (OS). Patients with left-sided CRC survive longer than those with right-sided CRC, amongthose treated with combination cetuximab and chemotherapy. However, no study has evaluated patient prognosisin terms of OS and progression-free survival (PFS) in relation to both tumor location and skin disorder. This studyaimed to determine the incidence of skin disorder according to tumor location and analyze the relationship of tumorlocation and skin disorder with OS. Methods: Patients with metastatic colorectal cancer (mCRC) treated with standardchemotherapy and cetuximab as first-line therapy were included. Differences in the incidence of skin disorders due tothe location of the primary tumors were compared in the same patient. The OS and PFS in relation to the location ofthe primary tumors and presence or absence of skin disorder were also compared. Results: Total frequency of eachskin disorder as rash acneiform, paronychia, and dry skin in patients with left- and right-sided mCRC was 70%, 70%,and 43% and 27%, 36%, and 27%, respectively. The median OS was 8.9 months for mCRC on the left-sided withoutskin disorder and 56.3 months for mCRC on the left-sided with skin disorder. In comparison, the median OS was 10.4months for mCRC on the right-sided without skin disorder and 11.3 months for mCRC on the right-sided with skindisease (left-sided with skin disorder versus other three group; P<0.001). Conclusions: Primary tumor location andthe presence of skin disorder are important factors in patients with mCRC who receive cetuximab. In particular, ourresults show the new fact that the left-sided and right-sided mCRC survival time were comparable if there is no skindisorder caused by cetuximab.     

Phase II Trial of Chemotherapy plus Bevacizumab as Second-Line Therapy for Patients with Metastatic Colorectal Cancer That Progressed on Bevacizumab with Chemotherapy: The Gunma Clinical Oncology Group (GCOG) trial 001 SILK Study

Objectives: BRiTE and ARIES (observational cohort studies) provided valuable information on continued use of bevacizumab (BV) beyond progression (BBP). This trial evaluates the efficacy and safety of BBP for patients with metastatic colorectal cancer that progressed on first-line chemotherapy. Methods: A total of 39 patients received FOLFIRI + BV (after FOLFOX + BV) or FOLFOX + BV (after FOLFIRI + BV) as protocol treatment. The primary endpoint was the response rate. Secondary endpoints were overall survival (OS), total survival from initiation of first-line treatment (TS), progression-free survival (PFS), and safety. Results: All 39 treated patients were evaluated for toxic effects. Two patients did not meet all of the eligibility criteria and were excluded from efficacy analyses. The response rate was 16.2%. The disease control rate was 76%. The median PFS was 150 days (range 117-224). The median OS was 417 days (range 233-813). The median TS was 988 days (range 600-1,268). Grade 3/4 adverse events (% of patients) related to treatment were neutropenia (33%), fatigue (23%), and hypertension (18%). Conclusions: This is the first report to show the effect of BBP in patients who had progressive disease on first-line treatment including BV confirmed by RECIST criteria. This analysis suggests the possibility of prolonged survival with continued use of BV.     

影响肝癌动脉灌注药物和栓塞治疗效果的因素分析

为了分析影响肝癌动脉灌注药物和栓塞治疗效果的因素，作者采用Ｌｏｇｉｓｔｉｃ回归多因素方法对９２例做肝动脉灌注化疗或栓塞治疗患者的１９个因素进行分析，结果显示：肿瘤有无包膜、Ｏｋｕｄａ分期、治疗方式是影响疗效的独立因素。作者认为做肝癌动脉灌注药物和栓塞治疗，应了解肿瘤包膜、临床分期情况，给予适当治疗。     

Correlation of Lactate Dehydrogenase Isoenzyme Profile With Outcome in Patients With Advanced Colorectal Cancer Treated With Chemotherapy and Bevacizumab or Cediranib: Retrospective Analysis of the HORIZON I Study

IntroductionBevacizumab improves outcome for patients with advanced colorectal cancer (CRC) when added to chemotherapy. The HORIZON I trial resulted in similar outcome with bevacizumab or cediranib, a small-molecule tyrosine kinase inhibitor of vascular endothelial growth factor (VEGF) receptor, as treatment of advanced CRC. The spectrum of lactate dehydrogenase (LDH) isoenzyme expression was examined in serum samples of HORIZON I participants to identify biomarkers predictive of efficacy of VEGF pathway inhibitors.Materials and MethodsTotal LDH levels, as well as LDH isoenzyme levels in frozen baseline serum samples, were retrospectively evaluated. Total LDH serum levels measured during the study, progression-free survival (PFS), and overall survival (OS) were available from the HORIZON I study data.ResultsTotal LDH levels measured in the frozen serum samples correlated with those measured in fresh samples. The expected reciprocal correlation was found between hypoxic and oxic LDH isoenzymes. High total LDH correlated with shorter PFS, and high hypoxia-related LDH isoenzymes correlated with shorter PFS and OS. The difference in outcome of the cediranib-treated patients vs. those treated with bevacizumab was not substantially different in the various LDH isoform expression subgroups. In patients with a hypoxic LDH pattern of expression, there was a nonsignificant trend of better outcome in cediranib-treated patients.ConclusionEvaluation of total LDH and its isoforms in frozen serum samples is feasible. High total LDH and high hypoxic LDH isoenzymes were associated with poor prognosis. Further studies are needed to evaluate the predictive value of LDH isoenzyme expression pattern for VEGF-pathway inhibition efficacy.     

Prognostic Factors in Patients with Stage II/III Breast Cancer Treated with Adjuvant Extension of Neoadjuvant Chemotherapy: A Retrospective Cohort Study with Ten-Years of Follow-Up Data

Purpose

The aim of this retrospective study was to identify the reliable long term prognostic factors in patients with stage II/III breast cancer who were treated with an adjuvant extension of neoadjuvant chemotherapy (NC).

Methods

Women under the age of 70-years, with previously untreated clinical stage II and III breast cancer, were treated with NC, which was comprised of three cycles of FEC (5-FU, epirubicin, and cyclophosphamide every 3 weeks) or MMM (methotrexate, mitoxantrone, and mitomycin-C every 3 weeks) with an adjuvant extension of three cycles of the same regimen.

Results

Cumulative 10-years disease-free survival (DFS) was 87.3% for patients with a good response and 55.5% for patients with no response (p=0.032); 92.9% for node negative patients, 75.0% for 1-3 positive nodes, 50.0% for 4-9 positive nodes and no survival for 10 or more positive nodes (p<0.001). Cumulative 10-years overall survival (OS) was 89.1% for patients with good response and 55.5% for patients with no response (p=0.024); 95.2% for node negative patients, 80.0% for 1-3 positive nodes, 50.0% for 4-9 positive nodes and no survival for 10 or more positive nodes (p<0.001). No significant difference was observed in DFS and OS between the FEC and MMM treated groups.

Conclusion

Based on a review of data with a long follow-up, only the clinical response to NC and the absolute number of metastatic axillary lymph node identified at surgical staging were independent predictors of both DFS and OS in patients with stage II/III breast cancer patients treated with adjuvant extension of NC.     

Front-Line Bevacizumab plus Chemotherapy with or without Maintenance Therapy for Metastatic Breast Cancer: An Observational Study by the Hellenic Oncology Research Group

Front-line bevacizumab (BEV) in combination with taxanes offers benefit in progression-free survival (PFS) in metastatic breast cancer (mBC). The medical records of mBC patients, treated with front-line BEV-based chemotherapy, were retrospectively reviewed in order to generate real life safety and efficacy data. Patients with human epidermal growth factor receptor 2 (HER2)-negative mBC treated with front-line BEV in combination with chemotherapy were eligible. Maintenance therapy with BEV and/or hormonal agents was at the physicians’ discretion. Among the 387 included patients, the most common adverse events were anemia (61.9%, mainly grade 1), grade 3/4 neutropenia (16.5%), grade 1/2 fatigue (22.3%), and grade 1/2 neuropathy (19.6%). Dose reductions were required in 164 cycles (7.1%) and toxicity led to treatment discontinuation in 21 patients (5.4%). The median PFS and the median overall survival (OS) were 13.3 (95% CI: 11.7–14.8) and 32.3 months (95% CI: 27.7–36.9), respectively. Maintenance therapy, with hormonal agents (ET) and/or BEV, was associated with longer OS versus no maintenance therapy (47.2 versus 23.6 months; p < 0.001) in patients with hormone receptor (HR)-positive disease and BEV maintenance offered longer OS versus no maintenance in patients with HR-negative disease (52.8 versus 23.3; p = 0.023). These real-life data show that front-line BEV-based chemotherapy in HER2-negative mBC patients is an effective treatment with an acceptable toxicity profile. The potential benefit of maintenance treatment, especially ET, is important and warrants further research.     

Prognostic and Predictive Impact of the HER-2/neu Extracellular Domain (ECD) in the Serum of Patients Treated with Chemotherapy for Metastatic Breast Cancer

BACKGROUND: The extracellular domain of the HER-2/neu -receptor (ECD) is shed from the receptor protein and can be detected in serum. However, the clinical implication of HER-2/neu ECD measurement must be further evaluated. METHODS: In patients with metastatic breast cancer participating in a trial on first-line chemotherapy, the association of serum HER-2/neu ECD with progression-free interval, survival, and response was studied. Blood samples of patients receiving epirubicin and either cyclophosphamide (EC) or paclitaxel (ET) were collected before (n = 103) and in addition, after three courses of therapy (n = 46). RESULTS: HER-2/neu ECD levels correlate with HER-2/neu overexpression of corresponding primary tumors determined by immunohistochemistry (antibody CB11, p = 0.018) with an optimized cut-off at 15 ng/mL. Elevated serum levels of HER-2/neu ECD before chemotherapy were correlated with shorter overall survival (p = 0.0097), but not with reduced progression-free survival and response to chemotherapy. In subgroup analyses, patients with elevated pretherapeutic HER-2/neu ECD levels treated with EC showed shorter overall survival (p = 0.0092); no difference was seen in the ET group. With regard to progression-free survival, patients with elevated HER-2/neu ECD levels tended to benefit from ET (p = 0.0341), in patients with low levels no difference was observed between EC and ET. A decrease of HER-2/neu ECD levels after three courses of therapy was associated with response to therapy (p = 0.006). CONCLUSION: In our group of metastatic breast cancer patients, elevated HER-2/neu ECD levels are associated with decreased overall survival. With regard to progression-free survival, particularly patients with high HER-2/neu ECD levels seem to benefit from taxane-containing chemotherapy.     

Prognostic Impact of the Advanced Lung Cancer Inflammation Index (ALI) in Metastatic Non-Small Cell Lung Cancer Treated with First Line Chemotherapy

Background: The advanced lung cancer inflammation index (ALI) has been reported to predict the overall survival in patients with advanced non-small cell lung cancer (NSCLC). However, no previous studies have examined the prognostic significance of ALI in metastatic NSCLC treated with first line chemotherapy. The objective of this study was to explore the relationship between ALI and the prognosis of metastatic NSCLC treated with first line chemotherapy. Materials and Methods: Data of 109 metastatic NSCLC patients who had completed first line treatment with chemotherapy was collected. A multivariate flexible parametric proportional-hazards model with restricted cubic splines (RCS) was used to explore and identify the independent prognostic factors, including clinical potential factors and ALI for the overall survival. Multivariate regression analysis was used to evaluate the potential prognostic factors associated with short survival less than 6 months. The analysis of the restricted mean survival time (RMST) method was used to estimate the event-free time from zero to 18 months. Results: The median OS was 10.9 months (95%CI 9.57-13.18) and median PFS was 7.5 months (95%CI 6.85-8.00).The multivariate survival analyses revealed two prognostic factors for worse survival: Poor ECOG PS (HR46.90; 95%CI 2.90-758.73; p=0.007) and progressive disease after completing the first line chemotherapy treatment (HR 2.85; 95%CI1.18-6.88; p=0.02),whereas a low ALI     

Meta-analysis of Excision Repair Cross-complementation Group 1 (ERCC1) Association with Response to Platinumbased Chemotherapy in Ovarian Cancer

Recent studies suggested that the ovarian cancers with negative excision repair cross-complementation group1 enzyme (ERCC1) expression have a better response to platinum-based chemotherapy than those with positiveERCC1 expression. The objective of this study was to evaluate whether ERCC1 expression is associated withresponse to platinum-based chemotherapy in ovarian cancers. MEDLINE, PubMed, Web of Science and CNKIdatabases were used for searching studies relating to ERCC1 protein expression and response to platinum-basedchemotherapy in ovarian cancers. Statistical analysis was based on the method for a fixed effects meta-analysis.Pooled odds ratios (ORs) with 95% confidence intervals for ERCC1 protein expression and response to platinumbasedchemotherapy were generated. Publication bias was investigated with Begg’s test. Five studies involving306 patients with ovarian cancer were included. Compared to patients with positive ERCC1 expression, thosewith negative ERCC1 expression had a better response to platinum-based chemotherapy. The pooled OR was5.264 (95% CI: 2.928 – 9.464, P < 0.001) and publication bias was not found (P = 0.904). The result was similarin both in Asians and Caucasians (P < 0.001 and P = 0.028, respectively). ERCC1 protein e     

158. Pathological Complete Response is not the Best Prognostic Factor in Patients with Breast Cancer Treated by Preoperative Chemotherapy

Aim of the study. Preoperative chemotherapy (pCHT) changes established prognostic markers. This study evaluated the prognostic value of pathological complete response (pCR) in comparison to other prognostic factors (PF) after a follow up of 6 years. Material and methods. One hundred and fifty-six patients with locally advanced breast cancer (clinically T2 or T3-tumors, M0) obtained pCHT with Epirubicin/Cyclophosphamid (3–4 cycles, 90/600 mg/m² every 3 weeks). Results. Seventy seven percentage of patients showed a remission of greater than 50% (n = 120) and a pCR in 6.4% (n = 10). Breast conserving surgery was performed in 68% (n = 106) of patients. Metastasis was seen in 38.4% (n = 60) of patients but only in two of patients with pCR (p = 0.146). Significant prognostic factors for DFS (disease-free survival) were the clinically assessed tumor size before pCHT (p = 0.009), the clinical nodal status before pCHT (p = 0.041), grading (p = 0.005), the histological tumor size after pCHT (p = 0.001), the histological axillary lymph node status after pCHT (p = 0.001) and the clinical response of the tumor to pCHT (p = 0.032). Regarding OAS (overall survival) only the grading and the pathological lymph node status proved to be statistically significant. Occurrence of pathological complete response did not prove to be a statistically significant marker. Regarding DFS grading (p < 0.001, RR = 2.49), histological tumor size after pCHT (p < 0.001, RR = 2.49) and the histological lymph node status (p < 0.001, RR = 2.11) proved to be independent prognostic factors in multivariate regression analysis. Looking at OAS histological lymph node status (p = 0.008, RR = 1.79) as well as grading (p = 0.001, RR = 3.48) remained independent prognostic factors. Summary. The most important prognostic factors after 6 years of follow up are the pathological lymph node status and the grading. Occurrence of pathological complete response was no statistically significant prognostic factor. Kind of pCHT and number of cycles could be responsible for this finding.     

Evaluation of pemetrexed (Alimta,LY231514) as second-line chemotherapy in persistent or recurrent carcinoma of the cervix: the CERVIX 1 study of the MITO (Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies) Group

BackgroundThe objective of the study was to estimate the antitumor activity of pemetrexed in patients with advanced/recurrent carcinoma of the cervix and to determine the nature and degree of toxicity.MethodsA multicenter phase II trial was conducted by the Multicentre Italian Trials in Ovarian Cancer and Gynecologic Malignancies (MITO) Group. Patients with advanced/recurrent measurable carcinoma of the cervix that had failed one prior chemotherapy regimen in association or not with radiotherapy were treated with pemetrexed at a dose of 500 mg/m² every 21 days. All the patients had a measurable lesion according to RECIST criteria in a not previously irradiated field.ResultsFrom November 2006 to September 2008, 43 patients were entered by seven member institutions of the MITO-Group. A total of 164 cycles (median 2, range 1–9) were administered. The treatment was well tolerated. More serious toxic effects (grades 3 and 4) included leukopenia in 27.9% and neutropenia in 30.2% of patients. No treatment-related deaths were reported. Six patients (13.9%) had partial responses (at least a 30% decrease in the sum of longest diameter of target lesions taking as reference the baseline sum longest diameter) with a median response of 7 weeks (range 3–27). Twenty-three patients (53.4%) had stable disease (less than a 50% reduction and less than a 25% increase in the sum of the products of two perpendicular diameters of all measured lesions and the appearance of no new lesions) and fourteen (32.5%) patients had progressive disease. Median progression-free survival was 10 weeks and overall survival was 35 weeks.ConclusionPemetrexed showed moderate activity against advanced/recurrent cervical cancer that had failed prior chemotherapy.     

Health-Related Quality of Life Analysis in Metastatic Colorectal Cancer Patients Treated by Second-Line Chemotherapy,Associated With Either Cetuximab or Bevacizumab: The PRODIGE 18 Randomized Phase II Study

Background and ObjectivesWe have previously showed that for patients with wild-type RAS metastatic colorectal cancer (mCRC) progressing after bevacizumab plus chemotherapy, bevacizumab continuation plus a switch of chemotherapy is the most appropriate option (PRODIGE 18 phase II study). Here we aimed to determine treatment impact in patient's Health-Related Quality Of Life (HRQoL) in PRODIGE18 study.MethodsHRQoL was evaluated in 2 arms bevacizumab or cetuximab—combined with chemotherapy (modified FOLFOX6 [mFOLFOX6] or FOLFIRI) using the European Organization for Research and Treatment of Cancer (EORTC) QLQ-C30 at baseline, first and third tumor evaluation and at the end of the study. The temporal evolution of quality of life scores was investigated using longitudinal linear mixed models of variance. The time until definitive deterioration (TUDD) was estimated using the Kaplan-Meier method and the long-rank test. A univariate Cox model was used to calculate HR with 95% CI. A multivariate Cox model was applied to determine association of TUDD with age and gender. Safety was assessed by the National Cancer Institute Common Terminology Criteria for Adverse Events.ResultsHRQoL QLQ-C30 questionnaire compliance was high at baseline (>90%) and declined over time (∼70% in tumor evaluation 1 and ∼ 60% in tumor evaluation 3), but remained similar in both treatment arms. Patient reported mean diarrhea QLQ-C30 score is significantly higher in bevacizumab treatment arm. Clinician reported mild diarrhea was more frequently declared in bevacizumab treatment arm. Cox multivariate analyses showed no statistically significant differences in TUDD for all QLQ-C30 scales between treatments. TUDD of appetite loss was significantly associated to age.ConclusionsOur study shows that no relevant impairment of patients HRQoL between the 2 treatment arms. So, the analysis of the HRQoL with equal effectiveness does not make it possible to favor one treatment over another.