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

Background:

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

Methods:

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

Results:

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

Conclusions:

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

Haemoptysis as a prognostic factor in lung adenocarcinoma after curative resection

Background:

Haemoptysis is a common symptom of lung cancer. Its prognostic role and mechanisms are still poorly understood.

Methods:

We retrospectively reviewed 666 consecutive patients with primary lung adenocarcinoma who underwent complete resection. The prognostic value of haemoptysis with respect to overall survival (OS), disease-specific survival (DSS) and disease-free survival (DFS) was analysed. To further explore the possible mechanisms of haemoptysis, we evaluated vascular endothelial growth factor (VEGF) expression, tumour necrosis, vascular invasion and extratumoural microvessel density (MVD) in 112 randomly selected patients.

Results:

Haemoptysis predicted poor OS, DSS and DFS in operable lung adenocarcinoma (all P<0.001). In addition, haemoptysis was associated with high white blood cell (WBC) count (P=0.032), high fibrinogen (Fib; P<0.001), high tumour greatest dimension (P<0.001), severe vascular invasion (P=0.002) and central tumour location (P<0.001). We obtained no statistically significant differences of VEGF expression, tumour necrosis and extratumoural MVD in haemoptysis and non-haemoptysis groups.

Conclusion:

Our study demonstrates that haemoptysis predicts poor OS, DSS and DFS in lung adenocarcinoma after curative resection. Vascular invasion rather than angiogenesis or tumour necrosis could be the most important mechanism of haemoptysis in lung adenocarcinoma.     

Results of postoperative radiochemotherapy of the patients with resectable gastroesophageal junction adenocarcinoma in Slovenia

Background.

Although the incidence of adenocarcinomas of the gastroesophageal junction (GEJ) is sharply rising in the Western world, there are still some disagreements about the staging and the treatment of this disease. The aim of this retrospective study was to analyse the effectiveness and safety of postoperative radiochemotherapy in patients with a GEJ adenocarcinoma treated at the Institute of Oncology Ljubljana.

Patients and methods.

Seventy patients with GEJ adenocarcinoma, who were treated with postoperative radiochemotherapy between January 2005 and June 2010, were included in the study. The treatment consisted of 6 cycles of chemotherapy with 5-FU and cisplatin and concomitant radiotherapy with the total dose of 45 Gy.

Results.

Twenty-six patients (37.1%) completed the treatment according to the protocol. The median follow-up time was 17.7 months (range: 3.3–64 months). Acute toxicity grade 3 or more, such as stomatitis, dysphagia, nausea or vomiting, and infection, occurred in 2.9%, 34.3%, 38.6% and 41.5% of patients, respectively. At 3 years locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS) were 78.2%, 25.3%, 35.8%, and 33.9%, respectively. In the multivariate analysis of survival, splenectomy and level of Ca 19-9 >20 kU/L before the adjuvant treatment were identified as independent prognostic factors for lower DFS, DSS and OS. Age <60 years, higher number of involved lymph nodes and advanced disease stage were identified as independent prognostic factors for lower DSS and OS.

Conclusions.

In patients with GEJ adenocarcinoma who first underwent surgery, postoperative radiochemotherapy is feasible, but we must be aware of a high risk of acute toxic side effects.     

The demographic features,clinicopathologic characteristics,treatment outcome and disease-specific prognostic factors of solitary fibrous tumor: a population-based analysis

Background

Solitary fibrous tumor''s (SFT) demographic features, clinicopathologic characteristics, treatment outcome and disease-specific prognostic factors were unexplored comprehensively.

Methods

SEER program was used to identify patients diagnosed with SFT from 1973 to 2012. Overall collected data were analyzed by using the SPSS 18.0.

Results

In total, 804 cases were found including 613 cases with SFT-specific mortality and 801 patients were analyzed for overall survival (OS). The 3-year disease specific survival (DSS), 5-year DSS and 10-year DSS were 73.3%, 65.7% and 53.3%. The 3-year OS, 5-year OS and 10-year OS were 71.9%, 63.3% and 47.3%. In the multivariate survival analysis, the age > 51 years (hazard ratio [HR] = 1.851 for DSS, P = 0.024 and HR = 1.652 for OS, P = 0.033; Reference [Ref] ≤ 51 years for DSS and ≤ 53 years for OS), SEER stage metastasized tumor (HR = 4.269 for DSS, P = 0.000 and HR = 2.905 for OS, P = 0.028, Ref - localized + regional tumor), pathologic grade III + IV (HR = 2.734 for DSS, P = 0.001 and HR = 2.585 for OS, P = 0.000, Ref - grade I + II) were adversely associated with DSS and OS. In addition, surgery was favorably associated with DSS (HR = 0.217, P = 0.045, Ref - surgery + radiotherapy).

Conclusions

The surgery was an independent prognostic factor for DSS. The patient''s age, SEER stage and pathologic grade were SFT-specific independent prognostic indicators for DSS and OS.     

The survival outcome and patterns of failure in node positive endometrial cancer patients treated with surgery and adjuvant radiotherapy with curative intent

Objective

The purpose of this study was to evaluate the patterns of failure, overall survival (OS), disease-free survival (DFS) and factors influencing outcome in endometrial cancer patients who presented with metastatic lymph nodes and were treated with curative intent.

Methods

One hundred and twenty-six patients treated between January 1996 to December 2008 with surgery and adjuvant radiotherapy were identified from our service''s prospective database. Radiotherapy consisted of 45 Gy in 1.8 Gy fractions to the whole pelvis. The involved nodal sites were boosted to a total dose of 50.4 to 54 Gy.

Results

The 5-year OS rate was 61% and the 5-year DFS rate was 59%. Grade 3 endometrioid, serous, and clear cell histologies and involvement of upper para-aortic nodes had lower OS and DFS. The number of positive nodes did not influence survival. Among the histological groups, serous histology had the worst survival. Among the 54 patients relapsed, only three (6%) failed exclusively in the pelvis and the rest of the 94% failed in extrapelvic nodal or distant sites. Patients with grade 3 endometrioid, serous and clear cell histologies did not influence pelvic failure but had significant extrapelvic failures (p<0.001).

Conclusion

Majority of node positive endometrial cancer patients fail at extrapelvic sites. The most important factors influencing survival and extrapelvic failure are grade 3 endometrioid, clear cell and serous histologies and involvement of upper para-aortic nodes.     

Lymph node density in oral cavity cancer: results of the International Consortium for Outcomes Research

Background:

Lymph node density (LND) has previously been reported to reliably predict recurrence risk and survival in oral cavity squamous cell carcinoma (OSCC). This multicenter international study was designed to validate the concept of LND in OSCC.

Methods:

The study included 4254 patients diagnosed as having OSCC. The median follow-up was 41 months. Five-year overall survival (OS), disease-specific survival (DSS), disease-free survival (DFS), locoregional control and distant metastasis rates were calculated using the Kaplan–Meier method. Lymph node density (number of positive lymph nodes/total number of excised lymph nodes) was subjected to multivariate analysis.

Results:

The OS was 49% for patients with LND⩽0.07 compared with 35% for patients with LND>0.07 (P<0.001). Similarly, the DSS was 60% for patients with LND⩽0.07 compared with 41% for those with LND>0.07 (P<0.001). Lymph node density reliably stratified patients according to their risk of failure within the individual N subgroups (P=0.03). A modified TNM staging system based on LND ratio was consistently superior to the traditional system in estimating survival measures.

Conclusion:

This multi-institutional study validates the reliability and applicability of LND as a predictor of outcomes in OSCC. Lymph node density can potentially assist in identifying patients with poor outcomes and therefore for whom more aggressive adjuvant treatment is needed.     

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.     

High levels of carbonic anhydrase IX in tumour tissue and plasma are biomarkers of poor prognostic in patients with non-small cell lung cancer

Background:

Carbonic anhydrase IX (CAIX) is an enzyme upregulated by hypoxia during tumour development and progression. This study was conducted to assess if the expression of CAIX in tumour tissue and/or plasma can be a prognostic factor in patients with non-small cell lung cancer (NSCLC).

Methods:

Tissue microarrays containing 555 NSCLC tissue samples were generated for quantification of CAIX expression. The plasma level of CAIX was determined by ELISA in 209 of these NSCLC patients and in 58 healthy individuals. The CAIX tissue immunostaining and plasma levels were correlated with clinicopathological factors and patient outcome.

Results:

CAIX tissue overexpression correlated with shorter overall survival (OS) (P=0.05) and disease-specific survival (DSS) of patients (P=0.002). The CAIX plasma level was significantly higher in patients with NSCLC than in healthy individuals (P<0.001). A high level of CAIX in the plasma of patients was associated with shorter OS (P<0.001) and DSS (P<0.001), mostly in early stage I+II NSCLC. Multivariate Cox analyses revealed that high CAIX tissue expression (P=0.002) was a factor of poor prognosis in patients with resectable NSCLC. In addition, a high CAIX plasma level was an independent variable predicting poor OS (P<0.001) in patients with NSCLC.

Conclusion:

High expression of CAIX in tumour tissue is a predictor of worse survival, and a high CAIX plasma level is an independent prognostic biomarker in patients with NSCLC, in particular in early-stage I+II carcinomas.     

Patterns of failure for stage I ampulla of Vater adenocarcinoma: a single institutional experience

Background

Ampullary adenocarcinoma is a rare malignancy associated with a relatively favorable prognosis. Given high survival rates in stage I patients reported in small series with surgery alone, adjuvant chemoradiotherapy (CRT) has traditionally been recommended only for patients with high risk disease. Recent population-based data have demonstrated inferior outcomes to previous series. We examined disease-related outcomes for stage I tumors treated with pancreaticoduodenectomy, with and without CRT.

Methods

All patients with stage I ampullary adenocarcinoma treated from 1976 to 2011 at Duke University were reviewed. Disease-related endpoints including local control (LC), metastasis-free survival (MFS), disease-free survival (DFS) and overall survival (OS) were analyzed using the Kaplan-Meier method.

Results

Forty-four patients were included in this study. Thirty-one patients underwent surgery alone, while 13 also received adjuvant CRT. Five-year LC, MFS, DFS and OS for patients treated with surgery only and surgery with CRT were 56% and 83% (P=0.13), 67% and 83% (P=0.31), 56% and 83% (P=0.13), and 53% and 68% (P=0.09), respectively.

Conclusions

The prognosis for patients diagnosed with stage I ampullary adenocarcinoma may not be as favorable as previously described. Our data suggests a possible benefit of adjuvant CRT delivery.     

Capecitabine in adjuvant radiochemotherapy for gastric adenocarcinoma

Background

In patients with non-metastatic gastric cancer surgery still remains the treatment of choice. Postoperative radiochemotherapy with 5-fluorouracil and leucovorin significantly improves the treatment outcome. The oral fluoropyrimidines, such as capecitabine, mimic continuous 5-fluorouracil infusion, are at least as effective as 5-fluorouracil, and such treatment is more comfortable for the patients.

Patients and methods.

In the period from October 2006 to December 2009, 101 patients with gastric cancer in stages Ib–IIIc were treated with postoperative chemoradiation with capecitabine. Distal subtotal resection of the stomach was performed in 46.3%, total resection in 50.5% and multivisceral resection in 3.2% of patients. The main endpoints of this study were loco-regional control (LRC), disease-free survival (DFS), disease-specific survival (DSS) and overall survival (OS). The rates of acute side-effects were also estimated.

Results

Seventy-seven percent of patients completed the treatment according to the protocol. The median follow-up time of all patients was 3.9 years (range: 0.4–6.3 years) and in survivors it was 4.7 years (range: 3.2–6.3 years). No death occurred due to the therapy. Acute toxicity, such as nausea and vomiting, stomatitis, diarrhoea, hand-foot syndrome and infections of grade 3 or 4, occurred in 5%, 1%, 2%, 8.9% and 18.8% of patients, respectively. On the close-out date 63.4% patients were still alive and with no signs of the disease. The 4-years follow-up survey showed that LRC, DFS, DSS and OS were 95.5%, 69.2%, 70.7%, and 66.2%, respectively. Higher pN-stage and splenectomy were found to be independent prognostic factors for all four types of survival and perineural invasion and lower treatment intensity for DFS, DSS and OS.

Conclusions

Postoperative radiochemotherapy with capecitabine is feasible, with low toxicity and the results of such treatment are good.     

Contribution of pelvic and para-aortic lymphadenectomy with sentinel node biopsy in patients with IB2-IIB cervical cancer

Objective:

Detection of lymph node involvement in women with IB2–IIB cervical cancer could have a positive effect on survival. We set out to evaluate the incidence of pelvic and/or para-aortic lymph node involvement using the sentinel node (SN) biopsy and its impact on survival.

Methods:

From 2002 to 2010, 66 women with IB2–IIB cervical cancer underwent a pelvic and paraaortic lymphadenectomy with SN biopsy. Survival between groups according to lymph node status was evaluated.

Results:

Mean tumour size was 43.5 mm. At least one SN was detected in 69% of the 45 SN procedures performed. Sixteen of these patients had metastatic SN and the false negative rate was 20%. Metastatic pelvic SNs or non-SNs were detected in 33 patients (50%), including pelvic-positive nodes in 26 (40%), pelvic- and paraaortic-positive lymph nodes in seven (11%), and paraaortic skip metastases in two (6%). Positive paraaortic node was the sole determinant for disease-free survival (DFS) and overall survival (OS; P<0.001). Differences in DFS and OS between groups according to the nodal status were observed (P<0.001).

Conclusion:

SN procedure gave a higher rate of metastasis detection. Further studies are required to evaluate whether pre-therapeutic node staging, including paraaortic and pelvic lymphanedectomy, should be performed.     

Lower tumour burden and better overall survival in melanoma patients with regional lymph node metastases and negative preoperative ultrasound

Background

The purpose of the study was to evaluate the ability of ultrasound (US) and fine needle aspiration biopsy (FNAB) in reducing the number of melanoma patients requiring a sentinel node biopsy (SNB); to compare the amount of metastatic disease in regional lymph nodes in SNB candidates with clinically uninvolved lymph nodes and of those with US uninvolved lymph nodes; and to compare the overall survival (OS) of both groups.

Methods

Between 2000 and 2007, a SNB was successfully performed in 707 patients with melanoma. The preoperative US of the regional lymph node basins was performed in 405 SNB candidates. In 14 of these patients, the US-guided FNAB was positive and they proceeded directly to lymph node dissection. In 391 patients, the preoperative US was either negative (343 patients) or suspicious (48 patients) (US group). In the remaining 316 patients the preoperative US was not performed (non-US group).

Results

The proportion of macrometastatic sentinel lymph nodes (SN), number of metastatic lymph nodes per patient and proportion of nonsentinel lymph node metastases were found to be lower in the US group compared to the non-US group. The smaller tumour burden of the US group was reflected in a significantly better OS of patients with SN metastases.

Conclusions

The preoperative US of regional lymph nodes spares some patients with melanoma from undergoing a SNB. Patients with regional metastases and a negative preoperative US have a significantly lower tumour burden in comparison to those with clinically negative lymph nodes, which is also reflected in a better OS.     

Treatment Outcome of Breast Cancer with Pathologically Proven Synchronous Ipsilateral Supraclavicular Lymph Node Metastases

Purpose

The aim of this study was to investigate the prognosis, patterns of failure, and prognostic factors for breast cancer patients with pathologically proven synchronous ipsilateral supraclavicular lymph node (ISCLN) metastases.

Methods

We reviewed the records of breast cancer patients with pathologically proven ISCLN metastases. Local aggressive treatment was defined as treatment including surgery, axillary lymph node dissection (ALND), ISCLN excision, radiotherapy (RT), and chemotherapy.

Results

A total of 111 patients were included. The 5-year overall survival (OS) and disease-free survival (DFS) rates were 64.2% and 56.2%, respectively. On univariate analysis, RT, ALND, trastuzumab treatment, hormone receptor (HR) status, and local aggressive treatment were identified as significant factors for OS. The 5-year OS for 73 patients who received local aggressive treatment was superior to that of 38 patients who received nonaggressive treatment (70.9% vs. 49.3%, p=0.036). Multivariate analysis showed that RT, HR status, and trastuzumab were significant variables for the 5-year OS and DFS.

Conclusion

Multimodality treatment with surgery, taxane-based chemotherapy, hormone therapy, and RT is strongly recommended for breast cancer patients with synchronous ISCLN metastases.     

Experiences of pretreatment laparoscopic surgical staging in patients with locally advanced cervical cancer: results of a prospective study

Objective

To prospectively evaluate the feasibility, safety, and survival of laparoscopic surgical staging in patients with locally advanced cervical cancer.

Methods

From Oct 2001 to Jul 2006, a total of 83 consecutive patients were eligible for inclusion and underwent laparoscopic surgical staging.

Results

Three patients with intraoperative great vessel injury and 1 patient in whom the colpotomizer was unable to be inserted were excluded. Laparoscopic surgical staging was feasible in 95.2% (79/83). Immediate postoperative complications were noted in 12 (15.2%) patients. Prolonged complications directly related to operative procedures numbered 2 (2.5%), and were trocar site metastases. The mean time from surgery to the start of radiotherapy (RT) or concurrent chemoradiotherapy (CCRT) was 11 (5-35) days. All patients tolerated the treatment well and completed scheduled RT or CCRT without disruption of treatment and additional admission. The rate of modification of the radiation field after surgical staging was 8.9% (7/79). Five-year progression-free survival and overall survival (OS) rates were 79% and 89%, respectively. The OS of patients with microscopic lymph node metastases, which were fully resected, were comparable to those of patients without lymph node metastasis. However, the OS of patients with macroscopic lymph node metastases that were fully resected were poorer compared with those of patients without lymph node metastasis.

Conclusion

Pretreatment laparoscopic surgical staging is a feasible and safe treatment modality. However the survival benefit of debulking lymph nodes or full lymph node dissection is not clear.     

The impact of combined radiation and chemotherapy on outcome in uterine papillary serous carcinoma compared to chemotherapy alone

Objective

To investigate the impact of pelvic radiation on survival in patients with uterine serous carcinoma (USC) who received adjuvant chemotherapy.

Methods

Patients with stage I-IV USC were identified from the Surveillance, Epidemiology, and End Results program 2000 to 2009. Patients were included if treated with surgery and chemotherapy. Patients were divided into two groups: those who received chemotherapy and pelvic radiation therapy (CT_RT) and those who received chemotherapy only (CT). Kaplan-Meier curves and Cox regression proportional hazard models were used.

Results

Of the 1,838 included patients, 1,272 (69%) were CT and 566 (31%) were CT_RT. Adjuvant radiation was associated with significant improvement in overall survival (OS; p<0.001) and disease-specific survival (DSS; p<0.001) for entire cohort. These findings were consistent for the impact of radiation on OS (p<0.001) and DSS (p<0.001) in advanced stage (III-IV) disease but not for early stage (I–II) disease (p=0.21 for OS and p=0.82 for DSS). In multivariable analysis adjusting for age, stage, race and extent of lymphadenectomy, adjuvant radiation was a significant predictor of OS and DSS for entire cohort (p=0.003 and p=0.05) and in subset of patients with stage III (p=0.02 and p=0.07) but not for patients with stage I (p=0.59 and p=0.49), II (p=0.83 and p=0.82), and IV USC (p=0.50 and p=0.96). Other predictors were stage, positive cytology, African American race and extent of lymphadenectomy.

Conclusion

In USC patients who received adjuvant chemotherapy, adjuvant radiation was associated with significantly improved outcome in stage III disease but not for other stages. Positive cytology, extent of lymphadenectomy and African race were significant predictors of outcome.     

Lymph node tissue kallikrein-related peptidase 6 mRNA: a progression marker for colorectal cancer

Background:

A most important characteristic feature for poor prognosis in colorectal cancer (CRC) is the presence of lymph node metastasis. Determination of carcinoembryonic antigen (CEA) mRNA levels in lymph nodes has proven powerful for quantification of disseminated tumour cells. Here, we investigate the utility of human tissue kallikrein-related peptidase 6 (KLK6) mRNA as a progression biomarker to complement CEA mRNA, for improved selection of patients in need of adjuvant therapy and intensified follow-up after surgery.

Methods:

Lymph nodes of pTNM stage I-IV CRC- (166 patients/503 lymph nodes) and control (23/108) patients were collected at surgery and analysed by quantitative RT–PCR.

Results:

Lymph node KLK6 positivity was an indicator of poor outcome (hazard ratio 3.7). Risk of recurrence and cancer death increased with KLK6 lymph node levels. Patients with KLK6 lymph node levels above the 90th percentile had a hazard ratio of 6.5 and 76 months shorter average survival time compared to patients with KLK6 negative nodes. The KLK6 positivity in lymph nodes with few tumour cells, that is, low CEA mRNA levels, also indicated poor prognosis (hazard ratio 2.8).

Conclusion:

In CRC patients, lymph node KLK6 positivity indicated presence of aggressive tumour cells associated with poor prognosis and high risk of tumour recurrence.     

Age as an independent prognostic factor for survival of localised synovial sarcoma patients

Background:

We performed a retrospective nationwide study to explore age as a prognostic factor in synovial sarcoma patients.

Methods:

Data on 613 synovial sarcoma patients were obtained from the Netherlands Cancer Registry. The prognostic relevance of age groups (children, adolescent and young adults (AYAs), adults, and elderly) was estimated by Kaplan–Meier survival curves and multivariable Cox-proportional hazards modelling.

Results:

A total of 461 patients had localised disease at diagnosis. The 5-year overall survival (OS) was 89.3±4.6%, 73.0±3.8%, 54.7±3.6%, and 43.0±7.0% in children (n=54), AYAs (n=148), adults (n=204), and elderly (n=55), respectively. Treatment modalities had no significant effect on survival in the univariable analysis. Multivariable analysis identified age at diagnosis, tumour localisation, and tumour size as significant factors affecting OS. Both tumour localisation and size were equally distributed over the age groups.

Conclusions:

We show that outcome of synovial sarcoma patients significantly decreases with age regardless of primary tumour site, size, and treatment.     

Cisplatin plus paclitaxel and maintenance of bevacizumab on tumour progression, dissemination, and survival of ovarian carcinoma xenograft models

Background:

Bevacizumab is being incorporated as first-line therapy with standard-of-care chemotherapy on epithelial ovarian carcinoma (EOC). We investigated bevacizumab combined with chemotherapy on tumour progression and mouse survival in EOC xenograft models.

Methods:

Bevacizumab was administered concomitantly with cisplatin plus paclitaxel (DDP+PTX), continued after induction (maintenance) or started after chemotherapy. The effect on tumour progression was monitored by bioluminescence imaging (BLI) (1A9-luc xenograft). Tumour dissemination into the peritoneal organs and ascites formation (HOC22 xenograft) was evaluated by histological analysis at the end of treatment (interim) and at euthanasia (survival). The effects on overall survival (OS) were investigated in both EOC models.

Results:

Bevacizumab with PTX+DDP delayed tumour progression in mice bearing EOC xenografts. OS was significantly extended, with complete responses, by bevacizumab continued after stopping chemotherapy in the HOC22 xenograft. Bevacizumab alone inhibited ascites formation, with only limited effect on tumour burden, but combined with PTX+DDP reduced ascites and metastases. Bevacizumab started after induction with PTX+DDP and maintained was equally effective on tumour progression and survival on 1A9-luc xenograft.

Conclusion:

Bevacizumab combined with chemotherapy not only affected tumour progression, but when administered as maintenance regimen significantly prolonged survival, reducing ascites, and tumour dissemination. We believe our findings are consistent with the clinical results and shed light on the potential effects of this kind of treatment on tumour progression.     

Long term outcome after combined modality treatment for anal cancer

Background

The aim of the retrospective study was to evaluate the effectiveness and toxicity of radiochemotherapy in patients with squamous cell carcinoma of the anal canal treated at a single institution.

Patients and methods

Between 1/2003 and 9/2010, 84 patients were treated with radical radiochemotherapy at the Institute of Oncology Ljubljana, Slovenia. The treatment consisted of 3-dimensional conformal external beam radiotherapy with concurrent chemotherapy (5-fluorouracil and mytomycin C), followed by brachytherapy or external beam boost. The toxicity of therapy and its effectiveness were assessed.

Results

The treatment was completed according to the protocol in 79.8% of patients. The median follow-up time of 55 survivors was 53 months (range: 16–105 months). The 5-year locoregional control (LRC), disease-free survival (DFS), disease-specific survival (DSS), overall survival (OS) and colostomy-free survival (CFS) rates were 71%, 68%, 81%, 67% and 85%, respectively. No treatment-related mortality was observed. The most frequent acute side-effect of the treatment was radiodermatitis (grade 3–4 in 58.2% of patients). LENT-SOMA grade 3–4 late radiation side effects were observed in 15 (18%) patients. In patients with brachytherapy boost a trend of less late side effects was observed compared to patients with external beam boost (P=0.066). On multivariate analysis, complete clinical disease response was identified as an independent prognostic factor for LRC, DFS and DSS, the salvage surgery for LRC and DFS, whereas Hb below 120 g/l retained its independent prognostic value for OS.

Conclusions

Radiochemotherapy provides an excellent disease control and the survival with preserving anal sphincter function in majority of patients. Surgical salvage with abdominoperineal resection for persistent or recurrent disease has curative potential.     

Statin use in primary inflammatory breast cancer: a cohort study

Background:

Some studies have suggested that statins, which have cholesterol-lowering and anti-inflammatory properties, may have antitumor effects. Effects of statins on inflammatory breast cancer (IBC) have never been studied.

Methods:

We reviewed 723 patients diagnosed with primary IBC in 1995–2011 and treated at The University of Texas MD Anderson Cancer Center. Statin users were defined as being on statins at the initial evaluation. Based on Ahern et al''s statin classification (JNCI, 2011), clinical outcomes were compared by statin use and type (weakly lipophilic to hydrophilic (H-statin) vs lipophilic statins (L-statin)). We used the Kaplan–Meier method to estimate the median progression-free survival (PFS), overall survival (OS) and disease-specific survival (DSS), and a Cox proportional hazards regression model to test the statistical significance of potential prognostic factors.

Results:

In the multivariable Cox model, H-statins were associated with significantly improved PFS compared with no statin (hazard ratio=0.49; 95% confidence interval=0.28–0.84; P<0.01); OS and DSS P-values were 0.80 and 0.85, respectively. For L-statins vs no statin, P-values for PFS, DSS, and OS were 0.81, 0.4, and 0.74, respectively.

Conclusion:

H-statins were associated with significantly improved PFS. A prospective randomised study evaluating the survival benefits of statins in primary IBC is warranted.