Expression of young HERV-H loci in the course of colorectal carcinoma and correlation with molecular subtypes

Background

Expression of the human endogenous retrovirus (HERV)-H family has been associated with colorectal carcinomas (CRC), yet no individual HERV-H locus expression has been thoroughly correlated with clinical data.Here, we characterized HERV-H reactivations in clinical CRC samples by integrating expression profiles, molecular patterns and clinical data. Expression of relevant HERV-H sequences was analyzed by qRT-PCR on two well-defined clinical cohorts (n = 139 pairs of tumor and adjacent normal colon tissue) including samples from adenomas (n = 21) and liver metastases (n = 16). Correlations with clinical and molecular data were assessed.

Results

CRC specific HERV-H sequences were validated and found expressed throughout CRC disease progression. Correlations between HERV-H expression and lymph node invasion of tumor cells (p = 0.0006) as well as microsatellite instable tumors (p < 0.0001) were established. No association with regard to age, tumor localization, grading or common mutations became apparent. Interestingly, CRC expressed elements belonged to specific young HERV-H subfamilies and their 5′ LTR often presented active histone marks.

Conclusion

These results suggest a functional role of HERV-H sequences in colorectal carcinogenesis. The pronounced connection with microsatellite instability warrants a more detailed investigation. Thus, HERV-H sequences in addition to tumor specific mutations may represent clinically relevant, truly CRC specific markers for diagnostic, prognostic and therapeutic purposes.     

CD8+ lymphocytes/?tumour-budding index: an independent prognostic factor representing a ‘pro-/anti-tumour' approach to tumour host interaction in colorectal cancer

Background:

The tumour-host interaction at the invasive front of colorectal cancer, including the epithelial–mesenchymal transition and its hallmark ‘tumour budding'', is an important area of investigation in terms of prognosis. The aim of this study was to determine the prognostic impact of a ‘pro-/anti-tumour'' approach defined by an established ‘pro-tumour'' (tumour budding) and host-related ‘anti-tumour'' factor of the adaptive immunological microenvironment (CD8+ lymphocytes).

Methods:

Double immunostaining for CK22/CD8 on whole tissue sections (n=279; Cohort 1) and immunohistochemistry for CD8+ using tissue microarrays (n=191; Cohort 2) was carried out. Tumour buds, CD8+ and CD8+ T-lymphocytes : tumour buds indices were evaluated per high-power field.

Results:

In Cohort 1, a low-CD8+/ buds index was associated with lymph node metastasis (P<0.001), vascular invasion (P=0.009), worse survival in univariate (P<0.001) and multivariable (P<0.001) analysis, and furthermore in lymph node-negative patients (P=0.002). In Cohort 2, the CD8+/ buds index was associated with T stage (P<0.001), N stage (P=0.041), vascular invasion (P=0.005) and survival in patients with TNM stage II (P=0.019), stage III (P=0.004), and adjuvantly untreated (P=0.009) and treated patients (P<0.001).

Conclusion:

The CD8+ lymphocyte : tumour-budding index is an independent prognostic factor in colorectal cancer and a promising approach for a future prognostic score for patients with this disease.     

pHH3 and survivin are co-expressed in high-risk endometrial cancer and are prognostic relevant

Background:

Phosphohistone-H3 (pHH3) is a promising reliable mitotic count biomarker. Our purpose was to study the relationship between the novel proliferation marker pHH3 and the established anti-apoptotic marker survivin and consider their prognostic relevance in endometrial cancer.

Methods:

A total of 106 patients with endometrial cancer (type I/endometrioid, n=81; type II carcinomas, n=18) and simple hyperplasia without atypia (n=7) were investigated. pHH3 and survivin expression were assessed using immunohistochemistry from paraffin-embedded tissue blocks.

Results:

A strong positive correlation was observed between pHH3 and survivin expression (P<0.0001). Patients with high-grade tumours and patients with type II carcinomas expressed significantly more pHH3 and survivin than low grade and endometrioid tumours (P<0.0001, P<0.0001, P<0.0001, and P<0.0001, respectively). In univariate survival analysis, overexpression of pHH3 and survivin were associated with increased recurrence and mortality (P<0.0001, P<0.0001, P<0.0001, and P<0.0001, respectively), in the multivariable Cox regression analyses both pHH3 and survivin could be identified as independent parameters for overall survival (P=0.004, and P=0.023, respectively).

Conclusion:

In endometrial cancer, pHH3 and survivin were strongly positive correlated and were both associated with type II and high-grade tumours. Increasing expression levels of pHH3 and survivin were associated with adverse prognostic factors.     

Digital pattern recognition-based image analysis quantifies immune infiltrates in distinct tissue regions of colorectal cancer and identifies a metastatic phenotype

Background:

Several studies in colorectal cancer (CRC) indicate a relationship between tumour immune infiltrates and clinical outcome. We tested the utility of a digital pattern recognition-based image analysis (DPRIA) system to segregate tissue regions and facilitate automated quantification of immune infiltrates in CRC.

Methods:

Primary CRC with matched hepatic metastatic (n=7), primary CRC alone (n=18) and primary CRC with matched normal (n=40) tissue were analysed immunohistochemically. Genie pattern recognition software was used to segregate distinct tissue regions in combination with image analysis algorithms to quantify immune cells.

Results:

Immune infiltrates were observed predominately at the invasive margin. Quantitative image analysis revealed a significant increase in the prevalence of Foxp3 (P<0.0001), CD8 (P<0.0001), CD68 (<0.0001) and CD31 (<0.0001) positive cells in the stroma of primary and metastatic CRC, compared with tumour cell mass. A direct comparison between non-metastatic primary CRC (MET−) and primary CRC that resulted in metastasis (MET+) showed an immunosuppressive phenotype, with elevated Foxp3 (P<0.05) and reduced numbers of CD8 (P<0.05) cells in the stroma of MET+ compared with MET− samples.

Conclusion:

By combining immunohistochemistry with DPRIA, we demonstrate a potential metastatic phenotype in CRC. Our study accelerates wider acceptance and use of automated systems as an adjunct to traditional histopathological techniques.     

Impact of systemic targeted agents on the clinical outcomes of patients with brain metastases

Background

To determine the clinical benefits of systemic targeted agents across multiple histologies after stereotactic radiosurgery (SRS) for brain metastases.

Methods

Between 2000 and 2013, 737 patients underwent upfront SRS for brain metastases. Patients were stratified by whether or not they received targeted agents with SRS. 167 (23%) received targeted agents compared to 570 (77%) that received other available treatment options. Time to event data were summarized using Kaplan-Meier plots, and the log rank test was used to determine statistical differences between groups.

Results

Patients who received SRS with targeted agents vs those that did not had improved overall survival (65% vs. 30% at 12 months, p < 0.0001), improved freedom from local failure (94% vs 90% at 12 months, p = 0.06), improved distant failure-free survival (32% vs. 18% at 12 months, p = 0.0001) and improved freedom from whole brain radiation (88% vs. 77% at 12 months, p = 0.03). Improvement in freedom from local failure was driven by improvements seen in breast cancer (100% vs 92% at 12 months, p < 0.01), and renal cell cancer (100% vs 88%, p = 0.04). Multivariate analysis revealed that use of targeted agents improved all cause mortality (HR = 0.6, p < 0.0001).

Conclusions

Targeted agent use with SRS appears to improve survival and intracranial outcomes.     

Simplified prognostic model in patients with oxaliplatin-based or irinotecan-based first-line chemotherapy for metastatic colorectal cancer: a GERCOR study

Background.

The present study was done to establish a prognostic model for patients and trials using an oxaliplatin-based or irinotecan-based first-line chemotherapy in metastatic colorectal cancer.

Patients and Methods.

Eight hundred three patients treated with FOLFOX or FOLFIRI in three prospective trials were randomly separated into learning (n = 535) and validation (n = 268) samples. Eleven baseline variables were evaluated in univariate and multivariate analysis as prognostic factors for overall survival, and a prognostic score was developed.

Results.

Independent prognostic factors identified in multivariate analysis for overall survival were performance status (PS) (p < .001), serum lactate dehydrogenase (LDH) (p < .001), and number of metastatic sites (p = .005). A prognostic score based on these three variables was found efficient (Harrell''s C index 0.61). This new model was improved by selecting only PS and LDH (Harrell''s C index 0.64). Three risk groups for death could be identified: a low-risk group (n = 184; median overall survival [OS] 29.8 months), an intermediate-risk group (n = 223; median OS 19.5 months), and a high-risk group (n = 128; median OS 13.9 months). Median survival for the low-, intermediate-, and high-risk groups were 26.8, 21.1, and 16.5 months, respectively, in the validation sample (Harrell''s C index 0.63).

Conclusions.

Serum LDH level was the main prognostic factor in predicting survival, followed by WHO PS. We identified three risk groups for death depending on these two baseline parameters. This simple prognostic model can be useful for clinician''s use and patient stratification in future clinical trials.     

Membranous expression of podocalyxin-like protein is an independent factor of poor prognosis in urothelial bladder cancer

Background:

Membranous expression of the anti-adhesive glycoprotein podocalyxin-like (PODXL) has previously been found to correlate with poor prognosis in several major cancer forms. Here we examined the prognostic impact of PODXL expression in urothelial bladder cancer.

Methods:

Immunohistochemical PODXL expression was examined in tissue microarrays with tumours from two independent cohorts of patients with urothelial bladder cancer: n=100 (Cohort I) and n=343 (Cohort II). The impact of PODXL expression on disease-specific survival (DSS; Cohort II), 5-year overall survival (OS; both cohorts) and 2-year progression-free survival (PFS; Cohort II) was assessed.

Results:

Membranous PODXL expression was significantly associated with more advanced tumour (T) stage and high-grade tumours in both cohorts, and a significantly reduced 5-year OS (unadjusted HR=2.25 in Cohort I and 3.10 in Cohort II, adjusted HR=2.05 in Cohort I and 2.18 in Cohort II) and DSS (unadjusted HR=4.36, adjusted HR=2.70). In patients with Ta and T1 tumours, membranous PODXL expression was an independent predictor of a reduced 2-year PFS (unadjusted HR=6.19, adjusted HR=4.60) and DSS (unadjusted HR=8.34, adjusted HR=7.16).

Conclusion:

Membranous PODXL expression is an independent risk factor for progressive disease and death in patients with urothelial bladder cancer.     

The association of diabetes with colorectal cancer risk: the Multiethnic Cohort

Background:

Diabetics have been found to have a greater risk of colorectal cancer than non-diabetics.

Methods:

We examined whether this relationship differed by ethnic group, cancer site or tumour stage in a population-based prospective cohort, including 3549 incident colorectal cancer cases identified over a 13-year period (1993–2006) among 199 143 European American, African American, Native Hawaiian, Japanese American and Latino men and women in the Multiethnic Cohort.

Results:

Diabetics overall had a significantly greater risk of colorectal cancer than did non-diabetics (relative risk (RR)=1.19, 95% confidence interval (CI)=1.09–1.29, P-value (P)<0.001). Positive associations were observed for colon cancer, cancers of both the right and left colon, and cancers diagnosed at a localised and regional/distant stage. The association with colorectal cancer risk was significantly modified by smoking status (P_Interaction=0.0044), with the RR being higher in never smokers (RR=1.32, 95% CI=1.15–1.53, P<0.001) than past (RR=1.19, 95% CI=1.05–1.34, P=0.007) and current smokers (RR=0.90, 95% CI=0.70–1.15, P=0.40).

Conclusion:

These findings provide strong support for the hypothesis that diabetes is a risk factor for colorectal cancer.     

Increased HMGB1 and cleaved caspase-3 stimulate the proliferation of tumor cells and are correlated with the poor prognosis in colorectal cancer

Background

Dying tumor cells after irradiation could promote the proliferation of living tumor cells might cause tumor relapse and treatment failure. Our previous study showed that activated caspase-3 after irradiation probably participates in tumor repopulation. In this study, we investigated whether high mobility group box 1(HMGB1) is also involved in tumor repopulation.

Methods

Colorectal tumor cells were irradiated. The cleaved caspase-3 (CC3) in irradiated tumor cells and HMGB1 in the supernatant of irradiated tumor cells were detected by Western blot. A large number of irradiated colorectal tumor cells (feeder cells) were then co-cultured with a small number of luciferase-labeled living colorectal tumor cells (reporter cells) and proliferation of reporter cells was measured by bioluminescence imaging. The CC3 and HMGB1 protein expression in colorectal tumor and peritumoral tissues were detected by immunohistochemistry and their correlation with prognosis were analyzed.

Results

The irradiated colorectal tumor cells underwent apoptosis and necrosis and produced CC3 in tumor cells and HMGB1 in the supernatant of cultured cells. The increased expression of secretory HMGB1 correlated with CC3 level and proliferating cell nuclear antigen (PCNA) after irradiation in vitro. The irradiated dying cells remarkably stimulated living tumor cell proliferation. Interestedly, immunohistochemistry staining showed that positive HMGB1, CC3, and Ki67 expression were significantly higher in colorectal tumor tissues than in peritumoral tissues (p <0.01). The Kaplan-Meier survival analysis revealed that high HMGB1, CC3, and Ki67 levels were significantly associated with poor prognosis (p <0.05, p <0.01). Multivariate analysis using Cox proportional hazards model showed that TNM staging and HMGB1 were independent prognostic factors in patients with colorectal cancer (CRC) (p <0.01, p <0.001).

Conclusion

Both apoptotic and necrotic cells could stimulate proliferation of living tumor cells, and the increased expression of CC3 and HMGB1 in tumor cells could be new markers for poor prognosis in colorectal cancer patients.

Electronic supplementary material

The online version of this article (doi:10.1186/s13046-015-0166-1) contains supplementary material, which is available to authorized users.     

LGR5 is associated with tumor aggressiveness in papillary thyroid cancer

PURPOSE

Leucine-rich repeat-containing G-protein-coupled receptor 5 (LGR5) is a cancer stem cell marker and a down-stream target in Wnt/β-catenin signaling. In human papillary thyroid cancer (PTC), over activation of Wnt/β-catenin has been associated with tumor aggressiveness.

PATIENTS AND METHODS

Using established human cell lines (TPC-1, KTC-1, Nthy-ori-3–1), we report LGR5 and R-spondin (RSPO1–3) overexpression in PTC and manipulate LGR5 and Wnt/β-catenin signaling via both pharmacologic and genetic interventions. We test the association of LGR5 tumor expression with markers of PTC aggressiveness using a Discovery Cohort (n = 26 patients) and a Validation Cohort (n = 157 patients). Lastly, we explore the association between LGR5 and the BRAFV600E mutation (n = 33 patients).

RESULTS

Our results reveal that LGR5 and its ligand, RSPO, are overexpressed in human PTC, whereby Wnt/β-catenin signaling regulates LGR5 expression and promotes cellular migration. In two separate cohorts of patients, LGR5 and RSPO2 were associated with markers of tumor aggressiveness including: lymph node metastases, vascular invasion, increased tumor size, aggressive histology, advanced AJCC TNM stage, microscopic extra thyroidal extension, capsular invasion, and macroscopic invasion. As a biomarker, LGR5 positivity predicts lymph node metastasis with 95.5% sensitivity (95% CI 88.8%-98.7%) and 61% specificity (95% CI: 48.4%–72.4%) and has a negative predictive value (NPV) of 91.3% (95% CI 79.2%–97.5%) for lymph node metastatic disease. In human PTC, LGR5 is also strongly associated with the BRAFV600E mutation (p = 0.005).

CONCLUSION

We conclude that overexpression of LGR5 is associated with markers of tumor aggressiveness in human PTC. LGR5 may serve as a future potential biomarker for patient risk stratification and loco regional metastases in PTC.     

Tumour-site-dependent expression profile of angiogenic factors in tumour-associated stroma of primary colorectal cancer and metastases

Background:

Tumour-associated stroma has a critical role in tumour proliferation. Our aim was to determine a specific protein expression profile of stromal angiogenic cytokines and matrix metalloproteinases (MMPs) to identify potential biomarkers or new therapy targets.

Methods:

Frozen tissue of primary colorectal cancer (n=25), liver (n=25) and lung metastases (n=23) was laser-microdissected to obtain tumour epithelial cells and adjacent tumour-associated stroma. Protein expression of nine angiogenic cytokines and eight MMPs was analysed using a multiplex-based protein assay.

Results:

We found a differential expression of several MMPs and angiogenic cytokines in tumour cells compared with adjacent tumour stroma. Cluster analysis displayed a tumour-site-dependent stromal expression of MMPs and angiogenic cytokines. Univariate analysis identified stromal MMP-2 and MMP-3 in primary colorectal cancer, stromal MMP-1, -2, -3 and Angiopoietin-2 in lung metastases and stromal MMP-12 and VEGF in liver metastases as prognostic markers (P>0.05, respectively). Furthermore, stroma-derived Angiopoietin-2 proved to be an independent prognostic marker in colorectal lung metastases.

Conclusion:

Expression of MMPs and angiogenic cytokines in tumour cells and adjacent tumour stroma is dependent on the tumour site. Stroma-derived MMPs and angiogenic cytokines may be useful prognostic biomarkers. These data can be helpful to identify new agents for a targeted therapy in patients with colorectal cancer.     

Weathering storms: a cohort study of how participation in a mindfulness-based stress reduction program benefits women after breast cancer treatment

Introduction

A growing number of psychosocial interventions are being offered to cancer patients during and after their medical treatment. Here, we examined whether Mindfulness-Based Stress Reduction (mbsr), a stress management course, helps women to cope better with stress and illness once their breast cancer treatment is completed. Our aim was to understand how mbsr may benefit those who participate in the course.

Methods

Our cohort study enrolled 59 women in an 8-week mbsr program. They completed “before and after” questionnaires pertaining to outcomes (stress, depression, medical symptoms) and process variables (mindfulness, coping with illness, sense of coherence). Paired t-tests examined changes from before to after the mbsr course. Changes in mindfulness were correlated with changes in post-mbsr variables, and a regression analysis examined which variables contributed to a reduction in stress after program participation.

Results

Adherence to the program was 91%. Participants reported significant reductions in stress (p < 0.0001), depression (p < 0.0001), and medical symptoms (p < 0.0001), and significant improvements in mindfulness (p < 0.0001), coping with illness (p < 0.0001), and sense of coherence (p < 0.0001). Changes in mindfulness were significantly related to changes in depression, stress, emotional coping, and sense of coherence. Increases in mindfulness and sense of coherence predicted reductions in stress.

Conclusions

It appears that learning how to be mindful is beneficial for women after their treatment for breast cancer.     

PTEN status in advanced colorectal cancer treated with cetuximab

Background:

Loss of phosphatase and tensin homologue deleted in chromosome 10 (PTEN) function in advanced colorectal cancer (CRC) may represent one of the resistance mechanisms to cetuximab by interfering with the epidermal growth factor receptor signal transduction pathway.

Methods:

PTEN expression tested by indirect immunofluorescence was evaluated both on primary (n=43) and on metastatic (n=24) sites in CRC patients treated with cetuximab.

Results:

The loss of PTEN expression tested on metastatic sites was negatively associated with response (100% progressive disease (PD) in PTEN-negative cases vs 30% PD in PTEN-positive cases; P<0.05), PFS (0.8 vs 8.2 months; P<0.001) and OS (2.9 vs 14.2 months; P<0.001).

Conclusion:

A potential role of PTEN in the anti-tumour activity of cetuximab could be hypothesised.     

The Association of Hospital Spending Intensity and Cancer Outcomes: A Population‐Based Study in an Asian Country

Background.

Different results are reported for the relationship between regional variation in medical spending and disease prognosis for acute illness and for cancer. Our objective was to investigate the association between hospital medical care spending intensity and mortality rates in cancer patients.

Methods.

A total of 80,597 patients with incident cancer diagnosed in 2002 were identified from the National Health Insurance Research Database of Taiwan, Republic of China. The Cox proportional hazards model was used to compare the 5-year survival rates of patients treated at hospitals with different spending intensities after adjusting for possible confounding and risk factors.

Results.

After adjustment for patient characteristics, treatment modality, and hospital volume, an association was found between lower hospital spending intensity and poorer survival rates. The 5-year survival rate expressed by hazard ratios was 1.36 (95% confidence interval [CI]: 1.30–1.43, p < .001) for colorectal cancer, 1.18 (95% CI: 1.08–1.29, p < .001) for lung cancer, 1.13 (95% CI: 1.05–1.22, p = .002) for hepatoma, 1.16 (95% CI: 1.07–1.26, p < .001) for breast cancer, and 1.23 (95% CI: 1.10–1.39, p = .001) for prostate cancer.

Conclusion.

Our preliminary findings indicate that higher hospital spending intensity was associated with lower mortality rates in patients being treated for lung cancer, breast cancer, colorectal cancer, prostate cancer, hepatoma, or head and neck cancer. The cancer stages were unavailable in this series, and more research linked with the primary data may be necessary to clearly address this issue.     

Promoter methylation of Wnt5a is associated with microsatellite instability and BRAF V600E mutation in two large populations of colorectal cancer patients

Background:

In colorectal cancer (CRC), tumour microsatellite instability (MSI) status and CpG island methylator phenotype (CIMP) status are indicators of patient outcome, but the molecular events that give rise to these outcomes remain largely unknown. Wnt5a is a critical regulator of non-canonical Wnt activity and promoter hypermethylation of this gene has emerging prognostic roles in CRC; however the frequency and prognostic significance of this epigenetic event have not been explored in the context of colorectal tumour subtype. Consequently, we investigated the frequency and prognostic significance of Wnt5a methylation in a large cohort of MSI-stratified CRCs.

Methods:

Methylation was quantified in a large cohort of 1232 colorectal carcinomas from two clinically distinct populations from Canada. Associations were examined between methylation status and clinicopathlogical features, including tumour MSI status, BRAF V600E mutation, and patient survival.

Results:

In Ontario, Wnt5a methylation was strongly associated with MSI tumours after adjustment for age, sex, and tumour location (odds ratio (OR)=4.2, 95% confidence interval (CI)=2.4–7.4, P<10⁻⁶) and with BRAF V600E mutation, a marker of CIMP (OR=12.3, 95% CI=6.9–21.7, P<10⁻¹⁷), but was not associated with patient survival. Concordant results were obtained in Newfoundland.

Conclusion:

Methylation of Wnt5a is associated with distinct tumour subtypes, strengthening the evidence of an epigenetic-mediated Wnt bias in CRC.     

Risk factors,short and long term outcome of anastomotic leaks in rectal cancer

Background

An anastomotic leak (AL) after colorectal surgery is one major reason for postoperative morbidity and mortality. There is growing evidence that AL affects short and long term outcome. This prospective German multicentre study aims to identify risk factors for AL and quantify effects on short and long term course after rectal cancer surgery.

Methods

From 1 January 2000 to 31 December 2010 381 hospitals attributed patients to the prospective multicentre study Quality Assurance in Colorectal Cancer managed by the Otto-von-Guericke-University Magdeburg (Germany). Included were 17 867 patients with histopathologically confirmed rectal carcinoma and primary anastomosis. Risk factor analysis included 13 items of demographic patient data, surgical course, hospital volume und tumour stage.

Results

In 2 134 (11.9%) patients an AL was diagnosed. Overall hospital mortality was 2.1% (with AL 7.5%, without AL 1.4%; p < 0.0001). In multivariate analysis male gender, ASA-classification ≥III, smoking history, alcohol history, intraoperative blood transfusion, no protective ileostomy, UICC-stage and height of tumour were independent risk factors. Overall survival (OS) was significantly shorter for patients with AL (UICC I-III; UICC I, II or III - each p < 0.0001). Disease free survival (DFS) was significantly shorter for patients with AL in UICC I-III; UICC II or UICC III (each p < 0.001). Rate of local relapse was not significantly affected by occurrence of AL.

Conclusion

In this study patients with AL had a significantly worse OS. This was mainly due to an increased in hospital mortality. DFS was also negatively affected by AL whereas local relapse was not. This emphasizes the importance of successful treatment of AL related problems during the initial hospital stay.     

Is It Important to Adapt Neoadjuvant Chemotherapy to the Visible Clinical Response? An Open Randomized Phase II Study Comparing Response-Guided and Standard Treatments in HER2-Negative Operable Breast Cancer

Background.

Neoadjuvant treatment provides a unique opportunity to evaluate individual tumor sensitivity. This study evaluated whether a response-guided strategy could improve clinical outcome compared with a standard treatment.

Methods.

Overall, 264 previously untreated stage II–III operable breast cancer patients were randomized to receive either standard treatment (arm A, n = 131), consisting of fluorouracil, epirubicin, and cyclophosphamide (FEC100: 500, 100, and 500 mg/m², respectively, for 3 cycles) followed by docetaxel (100 mg/m² for 3 cycles), or adapted treatment (arm B, n = 133), beginning with 2 cycles of FEC100 and switching to docetaxel if tumor size decreased by <30% after 2 cycles or <50% after 4 cycles of FEC100 (ultrasound assessments according to World Health Organization criteria). Otherwise, FEC100 was given for six cycles before surgery. Intent-to-treat analysis was performed.

Results.

Similar results were observed for clinical response (objective response was 54% vs 56%, p = .18), breast conservation surgery (BCS; 67% vs 68%, p = .97), and pathological complete response rate (Chevallier classification: 14% vs 11%, p = .68; Statloff classification: 16% vs 13%, p = .82) between arms A and B. Similar toxicities were observed, even with unbalanced numbers of FEC100 and docetaxel courses.

Conclusion.

Adapted and standard treatments had similar results in terms of tumor response, BCS rate, and tolerability. Further survival outcome data are expected.     

Circulating tumor cell count is a prognostic factor in metastatic colorectal cancer patients receiving first-line chemotherapy plus bevacizumab: a Spanish Cooperative Group for the Treatment of Digestive Tumors study

Background.

The Maintenance in Colorectal Cancer trial was a phase III study to assess maintenance therapy with single-agent bevacizumab versus bevacizumab plus chemotherapy in patients with metastatic colorectal cancer. An ancillary study was conducted to evaluate the circulating tumor cell (CTC) count as a prognostic and/or predictive marker for efficacy endpoints.

Patients and Methods.

One hundred eighty patients were included. Blood samples were obtained at baseline and after three cycles. CTC enumeration was carried out using the CellSearch® System (Veridex LLC, Raritan, NJ). Computed tomography scans were performed at cycle 3 and 6 and every 12 weeks thereafter for tumor response assessment.

Results.

The median progression-free survival (PFS) interval for patients with a CTC count ≥3 at baseline was 7.8 months, versus the 12.0 months achieved by patients with a CTC count <3 (p = .0002). The median overall survival (OS) time was 17.7 months for patients with a CTC count ≥3, compared with 25.1 months for patients with a lower count (p = .0059). After three cycles, the median PFS interval for patients with a low CTC count was 10.8 months, significantly longer than the 7.5 months for patients with a high CTC count (p = .005). The median OS time for patients with a CTC count <3 was significantly longer than for patients with a CTC count ≥3, 25.1 months versus 16.2 months, respectively (p = .0095).

Conclusions.

The CTC count is a strong prognostic factor for PFS and OS outcomes in metastatic colorectal cancer patients.     

Effect of hepatic arterial infusion chemotherapy of 5-fluorouracil and cisplatin for advanced hepatocellular carcinoma in the Nationwide Survey of Primary Liver Cancer in Japan

Background:

The efficacy of hepatic arterial infusion chemotherapy for the treatment of advanced hepatocellular carcinoma (HCC) remains unclear.

Methods:

The outcome of 476 patients with HCC who underwent hepatic arterial infusion chemotherapy with 5-fluorouracil and cisplatin (HAIC) were compared with 1466 patients who did not receive active therapy.

Results:

A survival benefit of the therapy after adjusting for known risk factors was observed (hazard ratio, 0.48; 95% CI, 0.41–0.56; P<0.0001). In propensity score-matched analysis (n=682), median survival time was longer for patients who underwent chemotherapy (14.0 months) than for patients who did not receive active treatment (5.2 months, P<0.0001).

Conclusion:

For advanced HCC, HAIC is considered to be an effective treatment.