Determinate Disease-free Survival Research Articles

Peri-operative and survival outcomes analysis of patients with endometrial cancer managed by three surgical approaches: a long-term Bulgarian experience.

The study aim was to assess the peri-operative, oncologic, and survival outcomes for patients with endometrial cancer (EC) managed by abdominal hysterectomy (AH), laparoscopic hysterectomy (LH), or robotic hysterectomy (RH) approaches at premier centers in Bulgaria. We analyzed histologically diagnosed EC cases operated via any of the three surgical methods during 2008-2019. Data analyses included patients and tumor characteristics, peri-operative outcomes, and disease status. We grouped FIGO stages I and II to represent early-stage EC and to investigate their survival. Kaplan-Meier and Cox regression analyses were performed to determine disease-free survival (DFS) and overall survival (OS). Consecutive 917 patients (AH = 466; LH = 60, RH = 391) formed the basis of study analyses. Most of demographics and tumor characteristics of the patients were comparable across the groups except few minor variations (e.g., LH/RH cases were younger, heavier, more stage IA, endometrioid, G1, low-risk group). LH and RH group cases had significantly lower operative time than AH (p < 0.001), shorter hospital length-of-stay (p < 0.001), higher post-operative Hgb (p < 0.001). RH cases had fewer blood transfusions than AH or LH (p < 0.001). Cox multivariate analyses indicate that OS was not influenced by the type of surgical approach. Despite the fact that the DFS in "early-stage" EC is significantly better in AH group than RH, the type of surgery (i.e., AH, LH, or RH) for "all stages" is insignificant factor for DFS. With our long-term experience, minimally invasive surgical approach resulted in superior peri-operative, oncologic, and survival outcomes. Specifically, RH is not only safe in terms of post-operative results, but also for mortality and oncologic rates.

Prognostic Significance of EMVI in Rectal Cancer in a Tertiary Cancer Hospital in India.

Background Presence of extramural venous invasion (EMVI) is a poor prognostic factor for rectal cancer as per literature. However, India-specific data are lacking. Aim The aim of the study is to determine the prognostic significance of EMVI in locally advanced rectal cancer on baseline MRI. Materials and Methods We retrospectively reviewed 117 MRIs of operable non-metastatic locally advanced rectal cancers in a tertiary cancer institute. Three dedicated oncoradiologists determined presence or absence of EMVI, and its length and thickness, in consensus. These patients were treated as per standard institutional protocols and followed up for a median period of 37 months (range: 2–71 months). Kaplan-Meier curves (95% CI) were used to determine disease-free survival (DFS), distant-metastases free survival (DMFS), and overall survival (OS). Univariate analysis was performed by comparing groups with log-rank test. Results EMVI positive cases were 34/114 (29%). More EMVI-positive cases developed distant metastasis compared with EMVI-negative cases (14/34–41% vs. 22/83–26%). The difference, however, was not statistically significant ( p = 0.146). After excluding signet-ring cell cancers ( n = 14), EMVI showed significant correlation with DMFS ( p = 0.046), but not with DFS or OS. The median thickness and length of EMVI was 6 and 14 mm, respectively in patients who developed distant metastasis, as compared with 5 and 11 mm in those who did not, although this difference was not statistically significant. Conclusion EMVI is a predictor of distant metastasis in locally advanced non-metastatic, non-signet ring cell rectal cancers. EMVI can be considered another high-risk feature to predict distant metastasis.

Outcomes of Post-Operative Treatment with Concurrent Chemoradiotherapy (CRT) in High-Risk Resected Oral Cavity Squamous Cell Carcinoma (OCSCC): A Multi-Institutional Collaboration.

Adjuvant chemoradiation (CRT), with high-dose cisplatin remains standard treatment for oral cavity squamous cell carcinoma (OCSCC) with high-risk pathologic features. We evaluated outcomes associated with different cisplatin dosing and schedules, concurrent with radiation (RT), and the effect of cumulative dosing of cisplatin. An IRB-approved collaborative database of patients (pts) with primary OCSCC (Stage I–IVB AJCC 7th edition) treated with primary surgical resection between January 2005 and January 2015, with or without adjuvant therapy, was established from six academic institutions. Patients were categorized by cisplatin dose and schedule, and resultant groups compared for demographic data, pathologic features, and outcomes by statistical analysis to determine disease free survival (DFS) and freedom from metastatic disease (DM). From a total sample size of 1282 pts, 196 pts were identified with high-risk features who were treated with adjuvant CRT. Administration schedule of cisplatin was not significantly associated with DFS. On multivariate (MVA), DFS was significantly better in patients without perineural invasion (PNI) and in those receiving ≥200 mg/m2 cisplatin dose (p < 0.001 and 0.007). Median DFS, by cisplatin dose, was 10.5 (<200 mg/m2) vs. 20.8 months (≥200 mg/m2). Our analysis demonstrated cumulative cisplatin dose ≥200 mg/m2 was associated with improved DFS in high-risk resected OCSCC pts.

Analysis of abdominal vs. robotic radical hysterectomies for patients with cervical cancer: a Bulgarian experience.

To assess and compare the peri-operative, oncologic, and survival outcomes for women with cervical cancer (CC) treated with abdominal radical hysterectomy (ARH) versus robotic radical hysterectomy (RRH) approaches in Bulgaria. We retrospectively analyzed patients with histologically diagnosed CC operated via ARH or RRH methods during January-2008 to April-2019. The data analyzed include patients and tumor characteristics, peri-operative outcomes, and disease status. Kaplan-Meier method and Cox regression analysis were performed to determine disease-free survival (DFS) and overall survival (OS). There were consecutive 1347 patients (ARH = 1006, RRH = 341), which formed the basis of study analyses. Women in the RRH group had significantly shorter median hospital length-of-stay than ARH cases (7 vs. 11days, p < 0.001), higher post-operative hemoglobin (116 vs. 108g/L, p < 0.001), and fewer blood transfusions (7.3% vs. 21.5%, p < 0.001), respectively. The overall incidence of post-operative complications was also lower in the RRH vs. ARH group (2.1% vs. 9.4%, p < 0.001). Median follow-up time for ARH vs. RRH groups was 4.32 vs. 5.24years, respectively (p < 0.001). Kaplan-Meier analysis demonstrated that the RRH cohort had a significantly higher survival rate compared to the ARH group (CC-specific death 8.5% vs. 16.5% respectively). Mean time to recurrence did not differ significantly in either surgical approach (p = 0.495). Cox multivariate regression showed no significant impact of surgical approach on DFS or OS. No significant difference in DFS or OS between ARH vs. RRH for CC was observed. RRH approach does not lead to inferior oncologic outcomes and is associated with better peri-operative outcomes. In regard to "all stages" of CC, we found robotic surgery safer compared to laparotomy, and thus consider RRH a better surgical treatment option for patients with CC.

Adjuvant Chemoradiotherapy for Gastric Tumors with D2 Dissection: A Controversial Problem

Objectives: What would be the optimal adjuvant therapy in operated gastric and gastro-esophageal junction (GEJ) adenocarcinoma patients who underwent D2 lymph node dissection remains to be a controversial issue in oncology. The objective of this study is to determine disease-free survival (DFS) and overall survival (OS) data in patients with gastric and GEJ adenocarcinoma with D2 dissected who receive adjuvant chemotherapy (CT) and adjuvant chemoradiotherapy (CRT), to examine the adverse effect profiles developed during treatment, to determine whether adding CRT to the treatment impacts the completion of adjuvant chemotherapy. Methods: Fifty-seven patients older than 18 years of age with D2 dissection, pathologically stage I-IIIC who received adjuvant CT and CRT treatment were included. Patients who were metastatic at the time of diagnosis, received neoadjuvant chemotherapy or CRT, did not have adequate follow-up and whose data could not be reached were excluded from the study. Results: In the study, while 3-year DFS was 60%, 3-year OS was 62.5%. 3-year OS was 53.3% for those with a performance score of 0-1 after CRT, while 3-year OS was 16% for those with a score of 2-3 (p=0.003). The 3-year DFS was 45% for those with 0-1 eastern cooperative oncology group (ECOG) performance score after CRT, while 3-year DFS was 16% for those with 2-3 (p=0.006). The estimated median OS and DFS were significantly shorter in 15 patients who could not complete adjuvant chemotherapy after CRT (75 months vs. 22 months for OS; p=0.00), (87 vs. 17 months for DFS; p<0.001). The most common adverse effect was fatigue (91%), and the most common hematological adverse effect was anemia (89.5%). Conclusion: Adding CRT to adjuvant chemotherapy in operated gastric and GEJ cancer patients who underwent D2 lymph node dissection might decrease the overall adjuvant treatment completion rate and the overall performance score of the patients and cause the risk of decreasing the success of adjuvant therapy by impacting the profile of adverse effects. Keywords: Adjuvant chemoradiotherapy, D2 dissection, gastric cancer

Role of pelvic exenteration in the treatment of persistent or recurrent gynecological cancers

Objective: Pelvic exenteration has been recognized as potentially curative for selected patients with persistent or recurrent gynecologic malignancies confined in the pelvis. Our main objective is to determine disease-free survival (DFS), overall survival (OS), and factors associated with recurrence.

Cyclin D1 G870A Polymorphism: Relation to the Risk of ALL Development, Prognosis Impact, and Methotrexate Cytotoxicity.

Background:Cyclin D1 (CCND1) regulates cell cycle progression during the late G1 and S phase and takes part in methotrexate metabolism. It was hypothesized that CCND1 gene polymorphism affects acute lymphoblastic leukemia (ALL) development, prognosis and may relate to methotrexate cytotoxicity. Subjects and methods:This study included 50 ALL patients and 50 healthy controls, CCND1 G870A polymorphism was studied in all items using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and evaluated methotrexate cytotoxicity for ALL patients using liver function tests before and after methotrexate treatment. We followed up patients for one year to determine disease-free survival (DFS) and overall survival (OS) and its relation to the CCND1 genotype. Results:We found that AA genotype and A allele have a higher risk of developing ALL compared to the control group. Additionally, we found no notable association between CCND1 variant and methotrexate cytotoxicity and no role of CCND1 polymorphism in ALL prognosis. Conclusion:Our results suggested that CCND1 G870A polymorphism is associated with a high risk of ALL development. However, it has no role in ALL prognosis or methotrexate cytotoxicity.

Hypermethylation of GADD45A Defines a Methylation Profile Distinct to Mutant IDH1/2, and Correlates with More Aggressive AML

We have previously reported that hypermethylationof the GADD45A promoter (GADD45AmeHI) occurs frequently in AML at a specific CpG residue (CpG1) and associates with poor overall survival for patients on standard chemotherapy (Perugini et al, Leukemia 2013). Sequenom multiplex analysis of 195 AML patients revealed a co-occurrence of GADD45AmeHI with recurrent mutations at conserved residues in IDH1 and IDH2 (p<0.0001, Fisher’s exact test). These mutations in IDH1 and IDH2 result in enzyme isoforms that produce high levels of the onco-metabolite 2-hydroxyglutarate with a wide-range of effects including inhibition of α-KG-dependent dioxygenases and association with a profound DNA hypermethylation phenotype in AML (Figueroa et al, Cancer Cell 2010). Furthermore these mutations are found in pre-leukemic AML clones (Shlush et al, Nature 2014) and lead to pre-leukaemic phenotypes in mouse models (Sasaki et al, Nature 2012, Kats et al, Cell Stem Cell 2014, Ogawara et al, Cancer Research 2015). Here we investigated the relationship between hypermethylation at GADD45A CpG1, IDH1/2 mutation status, global methylation patterns and patient survival.We performed survival analysis to determine disease-free survival (DFS) and relapse-free survival (RFS) for AML patients with GADD45AmeHI or IDH1/2-mutations. This showed that GADD45AmeHI is a significant independent predictor of poor DFS and RFS, particularly in normal karyotype AML (Cox regression analysis, NK-AML DFS, P=0.009 HR=2.55, RFS, P=0.003 HR=2.75). Despite the co-association of GADD45AmeHI with mutations in IDH1 and IDH2, the mutation status of IDH1/2 did not predict DFS or RFS in these patients. To examine further the relationship between GADD45AmeHI and IDH1/2-mutation, and to investigate how this might influence tumour cell biology in AML, we determined global methylation patterns for a panel of AML diagnosis (Dx) samples (base-pair-resolution analysis using enhanced reduced representation bisulfite sequencing; ERRBS) in which both GADD45AmeHI and IDH mutation status has been determined. Unsupervised analyses of global methylation patterns grouped the AML Dx samples into three clusters including cluster 1 (n=12) which was associated with GADD45AmeHI samples with IDH- mutations, cluster 2 (n=13) which was enriched for GADD45AmeHI lacking IDH- mutations, and cluster 3 (n=9) which was associated with GADD45AmeLO (low CpG1 methylation) IDH-WT AML. We propose that this CpG in the GADD45A promoter may be subject to alternative events affecting DNA methylation in AML pathogenesis, including events distinct from IDH1/2 mutation. Finally, in GADD45AmeHI AML we detected hypermethylated regions compared to CD34+ normal bone marrow controls within 2016 gene promoters, 848 of which were unique to the GADD45AmeHI samples and not present in IDH1/2-mutant samples. We hypothesize that these differentially methylated genes may contribute mechanistically to the poor survival observed for this subtype.To determine how GADD45AmeHI status might associate with disease progression, DNA methylation assessment was performed on the patient panel-matched relapse samples (Rx). While GADD45AmeHI occurs frequently in both cluster 1 and 2 there is a significant difference in level of GADD45A CpG1 methylation at Dx and Rx for samples in cluster 1 vs cluster 2 and 3 (Figure 1), consistent with mutant IDH1/2 activity influencing methylation levels at this CpG site. Given that GADD45A has an established basal role in the maintenance of genomic stability (Liebermann & Hoffman, Springer 2013), and is a determinant of HSC self-renewal and response to genotoxic insult (Wingert et al, Stem Cells 2016, Chen et al, Blood 2014) we are also investigating whether GADD45A methylation and silencing plays a direct role in determining aggressiveness and response to chemotherapy for GADD45AmeHIAML.In conclusion this data suggests that methylation at this specific CpGof the GADD45A promoter, in combination with IDH1/2 mutation status, associate with varying global methylation phenotypes. Importantly, we demonstrate that GADD45AmeHI better predicts poorer prognosis than IDH1/2 mutation status, despite the significant co-association of these characteristics in AML.SES and FEGB contributed equally to this work. [Display omitted] DisclosuresGuzman:Cellectis: Research Funding. Roboz:Agios, Amgen, Amphivena, Astex, AstraZeneca, Boehringer Ingelheim, Celator, Celgene, Genoptix, Janssen, Juno, MEI Pharma, MedImmune, Novartis, Onconova, Pfizer, Roche/Genentech, Sunesis, Teva: Consultancy; Cellectis: Research Funding. Levine:Qiagen: Membership on an entity's Board of Directors or advisory committees; Novartis: Consultancy. Melnick:Janssen: Research Funding.

Abstract 216: Pancreatic cancer fluorescence-­guided surgery with a fluorophore­-conjugated antibody to carcinoembryonic antigen (CEA) improves surgical resection and increases disease-free and overall survival in orthotopic mouse models

Abstract We established nude­ mouse models of human pancreatic cancer with surgical orthotopic implantation of the human BxPC­3 pancreatic cancer for fluorescence-guided surgery (FGS). After 2 weeks, mice then underwent bright-­light surgery (BLS) or FGS 24 hours after intravenous injection of anti CEA­-Alexa Fluor 488. Completeness of resection was assessed from postoperative imaging. Mice were followed postoperatively until premorbid to determine disease-free survival (DFS) and overall survival (OS). Complete resection was achieved in 92% of mice in the FGS group compared to 45.5% in the BLS group (p = 0.001). FGS resulted in a smaller postoperative tumor burden (p = 0.01). Cure rates with FGS compared to BLS improved from 4.5 to 40%, respectively (p = 0.01), and 1­year postoperative survival rates increased from 0% with BLS to 28% with FGS (p = 0.01). Median DFS increased from 5 weeks with BLS to 11 weeks with FGS (p = 0.0003). Median OS increased from 13.5 weeks with BLS to 22 weeks with FGS (p = 0.001). FGS resulted in greater cure rates and longer DFS and OS using a fluorophore-­conjugated anti ­CEA antibody. The present results demonstrate that FGS has potential to improve the surgical treatment of pancreatic cancer. Citation Format: Cristina A. Metildi, Sharmeela Kaushal, George A. Luiken, Robert M. Hoffman, Michael Bouvet. Pancreatic cancer fluorescence-­guided surgery with a fluorophore­-conjugated antibody to carcinoembryonic antigen (CEA) improves surgical resection and increases disease-free and overall survival in orthotopic mouse models. [abstract]. In: Proceedings of the 106th Annual Meeting of the American Association for Cancer Research; 2015 Apr 18-22; Philadelphia, PA. Philadelphia (PA): AACR; Cancer Res 2015;75(15 Suppl):Abstract nr 216. doi:10.1158/1538-7445.AM2015-216

Autologous Tumor Lysate-Pulsed Dendritic Cell Immunotherapy with Cytokine-Induced Killer Cells Improves Survival in Gastric and Colorectal Cancer Patients

Gastric and colorectal cancers (GC and CRC) have poor prognosis and are resistant to chemo- and/or radiotherapy. In the present study, the prophylactic effects of dendritic cell (DC) vaccination are evaluated on disease progression and clinical benefits in a group of 54 GC and CRC patients treated with DC immunotherapy combined with cytokine-induced killer (CIK) cells after surgery with or without chemo-radiotherapy. DCs were prepared from the mononuclear cells isolated from patients using IL-2/GM-CSF and loaded with tumor antigens; CIK cells were prepared by incubating peripheral blood lymphocytes with IL-2, IFN-γ, and CD3 antibodies. The DC/CIK therapy started 3 days after low-dose chemotherapy and was repeated 3–5 times in 2 weeks as one cycle with a total of 188.3±79.8×106 DCs and 58.8±22.3×108 CIK cells. Cytokine levels in patients' sera before and after treatments were measured and the follow-up was conducted for 98 months to determine disease-free survival (DFS) and overall survival (OS). The results demonstrate that all cytokines tested were elevated with significantly higher levels of IFN-γ and IL-12 in both GC and CRC cohorts of DC/CIK treated patients. By Cox regression analysis, DC/CIK therapy reduced the risk of post-operative disease progression (p<0.01) with an increased OS (<0.01). These results demonstrate that in addition to chemo- and/or radiotherapy, DC/CIK immunotherapy is a potential effective approach in the control of tumor growth for post-operative GC and CRC patients.

Elevated preoperative serum cancer antigen 15.3 levels are associated with reduced disease-free survival: a single-institution experience

We aimed to evaluate the prognostic significance of the preoperative tumor-marker cancer antigen (CA) 15.3 in Saudi patients with breast cancer and to find out whether any correlation exists between preoperative CA 15.3 and tumor size and nodal status. Preoperative blood samples for serum CA 15.3 levels were taken in 112 breast cancer patients who underwent breast-conserving surgery or modified radical mastectomy between February 1988 and August 2008. Serum levels of CA 15.3 below 35 U/mL were considered normal. The correlation between pre- and postoperative CA 15.3 levels with tumor size and nodal status was calculated using Pearson correlative coefficients. Kaplan-Meier curves were used to determine disease-free survival (DFS) according to CA 15.3 groups (<35, 36-100 and above >100 U/mL). The mean age of the cohort was 47.0 years (range 23-76, standard deviation 10.3). According to menopausal status, 93 patients (83.0%) were premenopausal, and 19 patients (17.0%) were postmenopausal. Mean preoperative CA 15.3 levels were 43.69 U/mL (1.0-209.87). Ten-year DFS rates were 100%, 84%, and 57.7% for CA 15.3 <35 U/mL, 36-100 U/mL, and >100 U/mL, respectively (P = 0.003). Preoperative CA 15.3 levels showed positive correlation with primary tumor size (R = 0.43, R (2) = 0.83, P = 0.03) and nodal status (R = 0.59, R (2) = 0.28, P < 0.0001), respectively. Elevated preoperative CA 15.3 above 35 U/mL in Saudi women breast cancer patients showed correlation with primary tumor size and nodal status, and preoperative CA 15.3 level is an independent prognostic factor for DFS. Preoperative serum CA 15.3 levels may be helpful for risk stratification along with other factors.

Tubular Carcinoma of the Breast: Clinicopathologic Features and Survival Outcome Compared with Ductal CarcinomaIn Situ

PurposeTubular carcinoma (TC) of the breast is an uncommon histological subtype of invasive breast cancer with an excellent prognosis compared with standard invasive ductal carcinoma. Recent studies suggested a possible precursor role for low grade ductal carcinoma in situ (DCIS) in the development of TC. The goal of this analysis was to understand the clinicopathologic features and outcomes of TC by comparing TC with DCIS.MethodsA retrospective review identified 70 patients with TC and 1,106 patients with DCIS between 1995 and 2011. Student t-test and Fisher exact test were used to compare the clinicopathologic characteristics of TC patients with those of DCIS patients. The Kaplan-Meier method and Cox regression analysis were used to determine disease-free survival (DFS) rates.ResultsCompared to DCIS, TC exhibited favorable clinicopathologic characteristics such as a lower nuclear grade (92.3%), higher expression of hormonal receptors (estrogen receptor-positive, 92.9%; progesterone receptor-positive, 87.0%), and less frequent overexpression of human epidermal growth receptor 2 (12.9%). DFS did not differ significantly between the TC and DCIS groups (5-year DFS, 100% vs. 96.7%; 10-year DFS, 92.3% vs. 93.3%; p=0.324), and cancer-specific deaths were not noted in either group. However, axillary lymph node involvement was observed in six (8.6%) of the 70 patients with TC. Three of these patients had small tumors (≤1 cm).ConclusionIn our study cohort, TC was associated with an excellent prognosis and a low rate of lymph node metastasis. However, lymph nodes metastases were found even in patients with small tumors (≤1 cm). Axillary staging must be considered for all patients with TC of the breast.

Can LMWH improve the outcome of patients with inoperable stage III non-small cell lung cancer?

Aim of the studyLung cancer is the most common malignancy, accounting for one-third of all deaths from cancer. Some studies have shown that low molecular weight heparin (LMWH) significantly prolongs the survival of patients with non-small cell lung cancer (NSCLC).The aim of this study was to determine the effects of treating inoperable stage III NSCLC with LMWH in addition to concurrent chemoradiotherapy.Material and methodsEighty-two patients with inoperable stage III NSCLC were evaluated at Dicle University's Medical Oncology Department between 2005 and 2010. All patients were treated with concurrent chemoradiotherapy (CRT) with or without LMWH (enoxaparin 4000 IU/day) depending on the patient's risk of thrombosis. The primary objectives were to determine disease-free survival (DFS) and overall survival (OS) for patients treated with LMWH.ResultsA total of 38 patients in the LMWH negative group and 44 patients in the LMWH positive group were included in the study. The median OS was 11.2 months for the enoxaparin recipients and 12.7 months for the non-enoxaparin group (p = 0.4). The median DFS was 9.3 months with CRT alone and 10.0 months with CRT plus enoxaparin (p = 0.9). The one-year OS rates were 47% and 34% for groups treated with CRT and enoxaparin plus CRT, respectively, while the two-year OS rates were 23% and 21%, respectively. No significant difference was noted between the two groups in terms of grade 3–4 hematologic toxicity and mucositis (p = 0.3).ConclusionsThis study did not demonstrate improvements in survival for patients with NSCLC treated with enoxaparin. LMWH's positive contribution is still controversial.

Long-term survival of endometrioid endometrial cancer patients

IntroductionTo establish risk factors for onset and progression of endometrioid endometrial cancer still remains the aim of scientists. The aim of the study was to determine disease-free survival (DFS) and overall survival (OS) in women with endometrioid endometrial cancer.Material and methodsA retrospective review of 142 patients with endometrioid endometrial cancer after surgery treated with adjuvant radiotherapy and/or chemotherapy in the Regional Cancer Centre in Lodz between 2002 and 2004 was performed. Clinical and pathological data were correlated with clinical outcome and survival.ResultsIn 3 patients (2.1%) clinical progression was diagnosed during the treatment. In 23 patients (16.7%) after primary remission, relapse was diagnosed 2-56 months after treatment. DFS and OS were 81.7% and 83.1% respectively. Better DFS significantly correlated with larger number of pregnancies (> 1), stage I of the disease and optimal surgery. Lower stage of disease, pelvic lymph node dissection, optimal surgery and depth of myometrial infiltration ≤ 50% were independent prognostic factors for better OS.ConclusionsThe results of our study provided significant evidence that early detection of endometrioid endometrial cancer enables optimal surgery. It reduces the indications for adjuvant therapy in stage I of the disease, and makes the prognosis significantly better. Other clinical and pathological factors such as numerous pregnancies, pelvic lymphadenectomy, and depth of myometrial infiltration, although important, are of less significance. Further prospective, randomized studies are necessary to prove the role of these factors.

A Retrospective Review of Association between Clinico-Pathologic Prognostic Factors and Disease Outcome in Node-Positive or High-Risk Node Negative Breast Cancer Patients Treated with Adjuvant Cyclophosphamide, Doxorubicin Followed by Paclitaxel: A Venezuelan Study.

Abstract Background: Breast cancer is a disease with a biologic and clinical heterogeneity explained by differences in the genetic composition, which translate into variability in estrogen receptor (ER), progesterone receptors (PR), Her2–Neu receptor (HER2) expression and permit to identify subgroups that show different prognoses and that also respond differently to treatment. The goal of this study was to determine disease-free survival (DFS) in relation to clinico-pathologic features and ER/PR/HER2 subgroups, in node-positive or high-risk breast cancer patients in a Venezuelan single institution. Methods: We reviewed data between May 1999 to July 2006, from our breast tumor registry with attention to clinical and pathologic prognostic factors. All patients were treated with either mastectomy or breast conserving surgery-with axillary node assessment for stage and adjuvant chemotherapy with doxorubicin 60mg/m2 and cyclophosphamide 600mg/m2 both IV day 1 x 4 cycles, followed by paclitaxel 175mg/m2 day 1 x 4 cycles every 3 weeks or every 2 weeks. All patient received radiation therapy and adjuvant hormonal therapy when indicated. Disease-free survival (DFS) was measured from the date of biopsy to the date of relapse. DFS was estimated using the univariate Kaplan-Meier method. Twelve clinico-pathologic factors that could influence relapse were selected and analyzed using the Cox Proportional Hazards Model. All analyses were carried out using Stata (version 6.0).Results: A total of 92 breast cancer patients all received adjuvant chemotherapy and radiotherapy, 79% of the patients received hormonal therapy with either Tamoxifen or an Aromatase Inhibitor according to their menopausal status. The median follow-up is 55.42 months (range 9.5-110 months). Median age was 50 years (27-70). Local and distant failures were 3% and 11% respectively. For the overall population, the probability of DFS at 2, 5 and 9 years was respectively 93%, 83% and 83%. The results of univariate analysis showed that the mayor significant prognostic factor for influencing relapse was Estrogen receptor (HR:0.29) (p=0.06). Univariate survival analyses comparing grade of differentiation, stage of disease and number of metastasis in axillary lymph nodes with respect to Disease-free survival were performed and showed no significant difference. Patients with triple negative tumors showed an increased risk of relapse with a significant decrease in 9-year disease-free survival 38.1% (p&amp;lt;0.001) and patients with ER+/PR+/HER2- had the best DFS 90% (p&amp;lt;0.001). Conclusions: Estrogen receptor expression was the most significant biologic prognostic factors for relapse in this population. Triple negative tumors were associated with worse DFS. Different DFS in ER/PR/HER2 subgroups clearly illustrates the heterogeneity of this disease and support the importance of tailored therapy in this era. Citation Information: Cancer Res 2009;69(24 Suppl):Abstract nr 6056.

Preoperative Chemotherapy Does Not Increase Morbidity or Mortality of Hepatic Resection for Colorectal Cancer Metastases

Hepatic metastasis from colorectal cancer (mCRC) is best treated with a multidisciplinary approach. Conflicting data exist regarding the impact of preoperative chemotherapy on morbidity and mortality after hepatectomy. We hypothesized that preoperative chemotherapy does not adversely impact complications or mortality associated with hepatectomy. A retrospective analysis was performed and included patients with mCRC who underwent hepatectomy from 1996 to 2006. Patients were separated into two groups: those who received preoperative chemotherapy and those who did not. Univariate and multivariate analyses were performed to determine the factors associated with morbidity and mortality. Kaplan-Meier analyses were performed to determine disease-free survival (DFS) and overall survival (OS). One hundred eighty-six patients were analyzed: 112 (60%) received preoperative chemotherapy for a median of 4.2 months. Eighty patients (43%) underwent major hepatectomy. When comparing the two groups, there were no differences in hepatic tumor size (median 3 cm; p = 0.35), type of resection (p = 0.62), stage (p = 0.44) or location (p = 0.10) of the primary tumor, preoperative carcinoembryonic antigen (CEA) level (p = 0.80), or number of nodes in lymphadenectomy (p = 0.62). Only number of positive nodes after colectomy (p = 0.02), age (p < or = 0.0001), and combined resection/radiofrequency ablation (RFA) (p = 0.004) were statistically different between the two groups. There was no difference in rates of morbidity (p = 0.81), mortality (p = 0.29), DFS (p = 0.25) or OS (p = 0.30). We conclude that the use of preoperative chemotherapy did not increase the risk of complications or death for patients undergoing hepatectomy for metastatic colorectal cancer. Pre-hepatectomy chemotherapy appears to be safe and is an important part of the multidisciplinary approach for this disease.