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Predictive Significance of Serum Level of Vascular Endothelial Growth Factor in Gastric Cancer Patients.

The study aims to evaluate serum VEGF expression in gastric cancer patients and investigate its relationship with clinicopathological parameters. We also examined the serum VEGF levels in GC patients having received surgery or chemotherapy treatment to assess its predictive and prognostic value as a biomarker. We enrolled 154 GC patients having not received neoadjuvant treatment and 100 healthy controls. In the treatment groups, 13 surgery patients and 15 chemotherapy patients were investigated. 42 chemotherapy patients with different chemotherapy efficacy were recruited as well. The serum VEGF was examined by ELISA. Serum VEGF level was remarkably upregulated in GC group compared with healthy group (p < 0.001). The serum VEGF level of GC group was significantly correlated with tumor cells differentiation degree, clinical stages, tumor infiltration depth, lymph node metastasis, and tumor size. The serum VEGF level of the 1 to 3 days after operation group was much lower than that of the preoperative group (p < 0.001) and the 7 days after operation group (p < 0.001). By contrast, serum VEGF level was decreased significantly after chemotherapy (p = 0.001). Importantly, serum VEGF level in PD+SD group was significantly higher compared to the PR+CR group (p = 0.011). Therefore, serum VEGF was a valuable biomarker in clinically monitoring the condition of GC patients.

Body Mass Index and Perioperative Complications After Esophagectomy for Cancer.

Given the increasing rate of obesity, the effects of excessive body weight on surgical outcomes constitute a relevant quality of care concern. Our aim was to determine the relationship between preoperative body mass index (BMI) on perioperative complications after esophagectomy for cancer. From our comprehensive esophageal cancer database consisting of 510 patients, we identified 166 obese (BMI ≥30), 176 overweight (BMI 25-29), and 148 normal-weight (BMI 20-24) patients. Malnourished patients (BMI of <20) were excluded. Incidence of preoperative risk factors and perioperative complications in each group were analyzed. The patient group consists of 420 men and 70 women with a mean age at time of surgery were 64 years (range 28-86 years). The categories of patients (obese, overweight, and normal-weight) were similar in terms of demographics and comorbidities, with the exception of a younger age (62.5 years vs 66.2 years vs 65.3 years, P = 0.002), and a higher incidence of diabetes (23.5% vs 11.4% vs 10.1%, P = 0.001) and hiatal hernia (28.3% vs 14.8% vs 20.3%, P = 0.01) for obese patients. More patients with BMI >24 were found with adenocarcinoma, compared with the normal-weight group (90.8% vs 90.9% vs 82.5%, P = 0.03). Despite similar preoperative stage, obese patients were less likely to receive neoadjuvant treatment (47.6% vs 54.5% vs 66.2%, P = 0.004). The type of surgery performed, overall blood loss, extent of lymphadenectomy, rate of resections with negative margins, and postoperative complications were not influenced by BMI on univariate and multivariate analysis. In our experience, BMI did not affect number of harvested lymph-nodes, rates of negative margins, and morbidity and mortality after esophagectomy for cancer. In our experience, esophagectomy could be performed safely and efficiently in mildly obese patients.

R1 rectal resection: look up and don't look down.

After rectal resection for adenocarcinoma, pathological examination may reveal invasion of the distal margin (DM) and/or a circumferential resection margin of the tumor (CRM-T) or of involved nodes (CRM-N) less than or equal to 1 mm. Such findings transform a planned R0 resection to R1. : The aim was to analyze the impact of an R1 resection on prognosis, recurrence rate, and choice of adjuvant treatment. All R1 resections observed between 2006 and 2011 were retrospectively collected. Patients were matched with 80 patients with R0 resections according to age, body mass index, gender, neoadjuvant treatment, type of resection, ypT/pT stages, and N stage. Among 472 rectal resections performed, 40 (8.5%) were R1 (CRM-T=34; CRM-N=11; invaded DM=4). Among the 4 patients with invaded DM, 3 underwent salvage abdominoperineal resection. Of the 12 patients who had not received neoadjuvant treatment, 5 received adjuvant radiotherapy. Mean follow-up was 49.3±29.3 months for the 120 patients; 5-year overall survival (OS) and disease-free survival (DFS) were 72% and 56%. Comparison between R0 and R1 resections showed a trend toward worse OS in R1 resections: 62% versus 79% (P=0.0954), a significantly worse DFS: 41% versus 65% (P=0.0267). Local recurrence rates were similar: 12% versus 13% (P=0.9177), whereas distant recurrence was significantly more frequent after R1 resection: 56% versus 26% (P=0.0040). R1 resection is associated with a worse prognosis, but local recurrence rate does not differ significantly from matched R0 resections. The difference was observed for distant recurrences, especially lung, favoring the use of chemotherapy and close surveillance of the thorax.

German Clinical Registries: Neoadjuvant Chemoradiotherapy in Non Small Cell Lung Cancer

ABSTRACT Aim: In 2000 and 2011 the “Arbeitsgemeinschaft Deutscher Tumorzentren (ADT)” and the “Kooperationsverband Qualitatssicherung durch klinische Krebsregister (KoQK)” collected the German data of clinical cancer registries for certain tumour entities using a standardized data sheet. These data were analyzed in February 2014, and we report the results for neoadjuvant therapy in non small lung cancer (NSCLC). Methods: A total of 129740 patients with NSCLC were submitted for analysis. Of 10819 (41.4%) in stage IIIA 9356 presented with stage IIIA (N2) (35.8%), while 15325 (58.6%) already had reached stage IIIB. Most often squamous cell carcinoma (52.3%) was diagnosed followed by adenocarcinoma (32.5%) and large cell carcinoma (5.2%), but a large percentage of “other non small cell lung cancer” (10%) were included. Results: “Neoadjuvant therapy” was documented in 1441 patients but 393 of these underwent chemoradiotherapy alone and did not proceed to surgery and thus were omitted in the further evaluation. In the remaining 1048 radiotherapy (n = 53), chemotherapy (n = 328) or chemoradiotherapy (n = 604) preceded surgery. Comparing patients who received neoaduvant therapy with patients who did not receive neoadjuvant treatment stages and gender showed no significant differences but patients receiving neoadjuvant treatment in the mean were younger (women 60 vs. 66 years, men 62 vs. 67 years). Patients who had been treated neoadjuvant lived longer (median 25 vs. 12 months) and showed better therapeutic response, but at the same time local relapses or metastases were registered more frequently. Conclusions: We conclude that patients who received neoadjuvant therapy lived longer. Whether this is due to their younger age (and probably better ECOG at diagnosis) can not be found out in this retrospective analysis of non-randomized patients. Disclosure: All authors have declared no conflicts of interest.

How reliable is immunohistochemical staining for DNA mismatch repair proteins performed after neoadjuvant chemoradiation?

Immunohistochemistry (IHC) testing for mismatch repair proteins (MMRP) is currently being used primarily in colorectal cancer resection specimens. We aimed to compare the results of IHC staining performed on biopsy specimens obtained at endoscopy with that performed on surgical specimens after neoadjuvant therapy. Thirty-two rectal cancer subjects had paired preneoadjuvant and postneoadjuvant tissue available for IHC staining (MLH1, MSH2, MSH6, and PMS2), whereas 39 rectosigmoid cancer patients who did not receive neoadjuvant treatment served as controls. Each slide received a qualitative (absent, focal, and strong) and quantitative score (immunoreactivity [0-3] × percent positivity [0-4]). The quantitative scores of MMRP from the operative material were significantly lower in the neoadjuvant group than in the control (P < .05 for all).The scores of all MMRP from endoscopic biopsies were not significantly different between the neoadjuvant and the control groups. Disagreement between the endoscopic biopsy and the operative material was evident in 23 of 128 stains (18.5%) in the neoadjuvant group and in 12 of 156 stains (7.7%) in the control group (P = .009). In the neoadjuvant group, a disagreement pattern of "endoscopic strong operative focal" was observed in 28.1% for PMS2, 12.5% for MSH6, 12.5% for MLH1, and 6.3% for MSH2, and in the control group, this same disagreement pattern was found in 12.8% for PMS2, 7.7% for MSH6, 7.7% for MLH1, and 0% for MSH2. Based on our findings, we suggest that for rectal cancer, the endoscopic material rather than the operative material should serve as the primary material for IHC staining.

Nomogram for predicting the benefit of neoadjuvant chemoradiotherapy for esophageal cancer: A SEER-Medicare analysis.

4073 Background: The impact of neoadjuvant chemoradiotherapy for esophageal cancer remains difficult to establish for specific patient (pt) populations. The primary aim of this study was to create a web-based prediction tool that provides individualized survival projections based on clinically relevant tumor and treatment data. Methods: Pts diagnosed with esophageal cancer between 1997 and 2005 were selected from the Surveillance, Epidemiology, and End Results (SEER) Medicare database. The covariates chosen for retrospective analysis were: sex, T and N stage, histology, total lymph nodes examined, and receipt of neoadjuvant chemotherapy (CT), radiotherapy (RT), or chemoradiotherapy (CRT). After weighting correction by treatment groups, a log logistic regression model for overall survival (OS) was selected based on goodness of fit analysis. Based on bootstrap resampling with 100 repetitions the Concordance Index (CI) was 0.703. Results: 1,128 resected esophageal pts that either did or did not receive neoadjuvant treatment were appropriate for analysis. On log logistic multivariate analysis: age, sex, T stage, N stage, number of lymph nodes harvested, receipt of neoadjuvant CRT, and receipt of chemotherapy were significantly associated with OS. All T stages greater than 1 benefitted from neoadjuvant CRT (p=&lt;0.001). No T stage benefitted from isolated neoadjuvant CT or RT. Patients with nodal metastases benefitted from neoadjuvant CRT (p=&lt;0.001) and CT (p=0.002). Conclusions: SEER-Medicare pts with resected esophageal cancer can be used to produce a survival prediction tool that can: 1) serve as a counseling and decision aid to pts and caregivers regarding their postoperative prognosis and 2) assist in research protocol design. Patients T2 or greater or with lymph node metastases benefitted from neoadjuvant CRT based on our data. This nomogram may underestimate the benefit of neoadjuvant CRT due to its variable downstaging effect on final pathologic stage. This web based tool is available for use at http://skynet.ohsu.edu/nomograms .

Decreased core muscle size is associated with worse patient survival following esophagectomy for cancer

Preoperative risk assessment, particularly for patient frailty, remains largely subjective. This study evaluated the relationship between core muscle size and patient outcomes following esophagectomy for malignancy. Using preoperative computed tomography scans in 230 subjects who had undergone transhiatal esophagectomy for cancer between 2001 and 2010, lean psoas area (LPA), measured at the fourth lumbar vertebra, was determined. Cox proportional hazards regression was employed to analyze overall survival (OS) and disease-free survival (DFS) adjusted for age, gender, and stage, and the Akaike information criterion was used to determine each covariate contribution to OS and DFS. Univariate analysis demonstrated that increasing LPA correlated with both OS (P = 0.017) and DFS (P = 0.038). In multivariate analysis controlling for patient and tumor characteristics, LPA correlated with OS and DFS in patients who had not received neoadjuvant treatment (n = 64), with higher LPA associated with improved OS and DFS. Moreover, LPA was of equivalent, or slightly higher importance than pathologic stage. These measures were not predictive among patients (n = 166) receiving neoadjuvant chemoradiation. Core muscle size appears to be an independent predictor of both OS and DFS, as significant as tumor stage, in patients following transhiatal esophagectomy. Changes in muscle mass related to preoperative treatment may confound this effect. Assessment of core muscle size may provide an additional objective measure for risk stratification prior to undergoing esophagectomy.

Prostate Cancers of Different Zonal Origin: Clinicopathological Characteristics and Biochemical Outcome After Radical Prostatectomy

To evaluate the effect of prostate cancer zonal origin on the biochemical outcome after radical prostatectomy, to analyze clinicopathological features of tumors arising in different zones and to test the ability of the nomogram to predict the probability of transition zone cancer at radical prostatectomy. Our cohort consisted of 1441 patients who underwent radical prostatectomy who did not receive neoadjuvant treatment. Clinicopathological characteristics and biochemical outcomes were compared between the groups of men with different zonal location of prostate cancer. Performance of the nomogram in predicting cancer location was evaluated with respect to discrimination and calibration. The rates of positive margin were similar in men with transition zone and mixed tumors and were significantly higher than those with peripheral zone tumors. Most of the positive margins in patients with transition zone and mixed cancers were located at the apico-anterior part of the gland. On multivariate analysis, transition zone cancer location was associated with better biochemical recurrence-free survival (P = .043). The Harrel c-index of the models that did and did not include zonal origin of cancer was 0.810 and 0.807, respectively. Performance of the nomogram was poor. The association between transition zone tumor origin and the risk of biochemical recurrence does not add important predictive value to the standard prognostic factors. Although information about the risk of prostate cancer involvement of the transition zone may be important for surgical planning, our ability to predict this risk preoperatively is limited.

Accuracy of computed tomography in staging colon cancer patients.

614 Background: Though adjuvant chemotherapy is well-established for treating patients with AJCC Stage III colon cancer, there is growing interest in giving chemotherapy neoadjuvantly for these patients. Since clinical staging to determine eligibility requires accurate preoperative imaging, our objective was to determine whether computed tomography (CT) scans can be used to detect nodal disease in colon cancer patients. Methods: We identified patients with AJCC stage I-III colon cancer who underwent curative resection between 2006 and 2010 at our institution. Patient CT scans were obtained and final radiologic reports were recorded in a database. CT images underwent secondary prospective review by a blinded independent surgeon with the intent to identify mesenteric lymphadenopathy (N+). Clinical staging from the original radiologic report and secondary surgeon review of the CT images were then compared with pathologic staging. Results: Imaging and pathology were available for 67 colon cancer patients. Original radiologic review reported N+ disease in 10 of 67 patients (15%), but final pathology revealed 31 of 67 (46%) patients to be N+. Therefore, radiological review correctly predicted Stage III disease in 10 of 31 (32%) patients. On final pathology, 36 of 67 (54%) patients had no nodal disease (N0). Radiologic reports noted absence of lymphadenopathy in 29 of 67 (43%) patients, thus accurately predicting N0 disease in 29 of 36 (80%) patients. Of 67 studies, 14 (21%) had no mention of lymphadenopathy and were considered N0. Of these 14, 6 were N+ on final pathology. Surgeon review accurately identified N+ disease in 4 of these 6 patients. On surgeon review, sensitivity increased from 32% to 68% while specificity dropped from 80% to 61%, corresponding to a decrease in false negatives from 68% to 32% and an increase in false positives from 20% to 39%. Conclusions: Current clinical staging of colon cancer by CT has low accuracy. However, actively seeking nodal disease improves sensitivity but with minor loss of specificity. Improved radiologic criteria and technology may further increase accuracy in clinical staging of Stage III colon cancer patients who will receive neoadjuvant treatment.

Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial

We compared the efficacy and safety of the addition of lapatinib versus trastuzumab to anthracycline-taxane-based neoadjuvant chemotherapy. In the GeparQuinto randomised phase 3 trial, patients with untreated HER2-positive operable or locally advanced breast cancer were enrolled between Nov 7, 2007, and July 9, 2010. Patients were eligible if their tumours were classified as cT3/4a-d, or hormone receptor (HR)-negative, HR-positive with clinically node-positive and cT2 disease (cT2 cN+), or HR-positive and pathologically node-positive in the sentinel lymph node for those with cT1 disease (cT1 pN(SLN+)). Patients were randomly assigned in a 1:1 ratio to receive neoadjuvant treatment with four cycles of EC (epirubicin [90 mg/m(2) intravenously] plus cyclophosphamide [600 mg/m(2) intravenously], every 3 weeks), and four cycles of docetaxel (100 mg/m(2) intravenously every 3 weeks) with either trastuzumab (6 mg/kg intravenously, with a starting loading dose of 8 mg/kg, for eight cycles, every 3 weeks) or lapatinib (1000-1250 mg per day orally) throughout all cycles before surgery. Randomisation was done by dynamic allocation with the minimisation method of Pocock and patients were stratified by participating site, HR status, and extent of disease (cT1-3 cN0-2 vs T4 or N3). The primary endpoint was pathological complete response (defined as ypT0 and ypN0) and was analysed in all patients who received at least one cycle of EC. Participants and investigators were not masked to treatment assignment. Pathologists in centres assessing surgery outcomes were masked to group assignment. This trial is registered with ClinicalTrials.gov, number NCT00567554. Of 620 eligible patients, 309 were randomly assigned to chemotherapy with trastuzumab (ECH-TH group) and 311 to chemotherapy with lapatinib (ECL-TL group). Two patients in the ECH-TH group and three patients in the ECL-TL group did not start treatment because of withdrawal of consent or immediate surgery. 93 (30·3%) of 307 patients in the ECH-TH group and 70 (22·7%) of 308 patients in the ECL-TL group had a pathological complete response (odds ratio [OR] 0·68 [95%CI 0·47-0·97]; p=0·04). Chemotherapy with trastuzumab was associated with more oedema (119 [39·1%] vs 88 [28·7%]) and dyspnoea (90 [29·6%] vs 66 [21·4%]), and ECL-TL with more diarrhoea (231 [75·0%] vs 144 [47·4%]) and skin rash (169 [54·9%] vs 97 [31·9%]). 43 (14·0%) patients discontinued in the ECH-TH group and 102 (33·1%) in the ECL-TL group. 70 serious adverse events were reported in the ECH-TH group and 87 in the ECL-TL group. This direct comparison of trastuzumab and lapatinib showed that pathological complete response rate with chemotherapy and lapatinib was significantly lower than that with chemotherapy and trastuzumab. Unless long-term outcome data show different results, lapatinib should not be used outside of clinical trials as single anti-HER2-treatment in combination with neoadjuvant chemotherapy. GlaxoSmithKline, Roche, and Sanofi-Aventis.

P3-07-37: Clinical Characteristics and Treatment of Brazilian Women with Breast Cancer at Public and Private Institutions.

Abstract Background: Breast cancer is the most common type of cancer among Brazilian women with almost 50.000 new cases per year. There are few data regarding the clinical presentation, treatment and specially outcome of this population. Brazilian health system is composed by Public institutions (Pu); Private centers (Pr) and some institutions that assist both Public and Private patients (PuPr). Material and Methods: We collected data from 17 cancer centers distributed throughout Brazil among Pu; Pr and PuPr centers. We've analyzed data from 1-clinical characteristics, 2- pathologic characteristics and 3-type of treatment received among 2435 patients from May 2008 to May 2009. Results: Mean age at diagnosis was 53 years, with about 30% below age 50. Most of the cases were Invasive Ductal Cancer (83%). Stage 0 was seen in 3.2%, Stage I in 21,8%, Stage II in 46,6%, Stage 3 in 24,6% and Stage IV in 3,9 %. Clinical Stage III + IV was seen in 18,5% of the Pu institutions, only 3,7% of the Pr ones and about 6,2% among those PuPr. Hormone receptors were positive in 55%. Her-2 was overexpressed in 27,3% of the patients, and triple negative were seen in 11,6%. Most of the patients were submitted to surgery (92,9%). In Pu institutions only 36% of the patients were submitted to Breast Conserving Surgery (BCS) and in the Pr institutions 49,4% of the patients were submitted to BCS and in the PuPr 47%. Breast reconstruction was made in 15,8% and did not differ between Pu and Pr institutions. Sentinel node biopsy was done in 30,6% of the patients (26,8% of the patients from the Pr institutions and 26,8% of the Pu ones and 33% among PuPr). Neoadjuvant treatment was done in 21,5% of the patients (Pu=27,2%; Pr=13,9% and PuPr 13,2%). Most of this neoadjuvant treatment was chemotherapy (93,8%) and only 4,3% was hormonetherapy (HT). 30% of the patients received AC, 41% A+taxane and 18,9% FAC/FEC. Besides we have almost 30% of Her-2 overexpressed only 1,1% of the patients received trastuzumab in the neoadjuvant setting. Tamoxifen was used in 48,3% when neoadjuvant HT was done, and aromatase inhibitor (AI) was used in 34,5%. Most of the patients received any kind of adjuvant treatment (89,2%). Chemotherapy was done in 76,6% and hormonetherapy in 69,8%. When chemotherapy was used the preference regiment was FAC/FEC (27,3%), followed by CMF (17,5%) and AC (11,9%). Trastuzumab was use in only 5,8% of the patients (Pu=6,8%, Pr=18,3% and PuPr 3% among all patients that received chemotherapy). In the adjuvant setting, Tamoxifen (TAM) was prescribed in 69,8% of the cases (Pu=87,6%, Pr=79,6% and PuPr 78,8%), AI in 8,2% (Pu=5,9%, Pr=9,3% and PuPr 13,8%), and sequential TAM/AI in 6,6% (Pu=6,1%, Pr=8,3% and PuPr 6,4%). About 17% of the patients had metastasis. Conclusions: There are important differences between the public and private institutions in Brazil, the patients from the Pu institutions were five times more likely to be diagnosed in stage III or IV, they usually receive neoadjuvant treatment, and when surgery was done, most of them were treated with radical procedures. Besides the overexpression of Her-2 (30%) a minority of the patients received treatment with trastuzumab even for the Private centers (high cost for a developing country). Citation Information: Cancer Res 2011;71(24 Suppl):Abstract nr P3-07-37.

Emlődaganatos betegek primer szisztémás terápiája során elért eredményeink (2007–2010)

The importance of preoperative neoadjuvant (NA) systemic treatment in operable breast cancer has significantly increased in the last few years. The aim of our retrospective study was to determine the effect of NA therapy in breast cancer patients treated in our unit and analyze radiological and pathological response rates in the context of surgical treatment. One hundred and fourteen cases of breast cancer with NA therapy were analyzed and clinical data were collected from March 2007 to December 2010. Twenty-two patients received NA treatment for inoperable tumours. As far as operable cancers (92 patients), the indications for NA treatment were high tumour grade, presence of axillary metastasis and relatively young age. 5-Fluorouracil-Epirubicin-Cyclophosphamid or Taxotere-Epirubicin regimens were administered in 6 cycles followed by radiological evaluation and surgery. Herein, we compared the preoperative staging with the pathological results after surgery. NA therapy resulted in complete regression in 17% of patients, significant regression in 21%, while moderate regression was achieved in 43% of patients. No regression was detected in 19%. The decrease in T stage was not followed by decrease in N stage in significant number of cases. Moreover, in some cases NA therapy caused complete radiological regression, while histologically it still remained positive. In certain cases, breast conserving surgery was feasible due to down-staging caused by NA therapy. NA therapy was effective primarily in decreasing tumour size; however, it was less effective on axillary lymph node metastases. Due to the presence of the residual DCIS component, the volume of resection could not be decreased as much as down-staging of the invasive cancer would have permitted.

Neoadjuvant therapy and rates of margin re-excision in patients with invasive breast cancer.

131 Background: Many patients with invasive breast cancer receive neoadjuvant chemotherapy (NACT) prior to undergoing definitive surgical management in an effort to facilitate breast conservation. This study compares the re-excision rates of patients undergoing NACT with those who proceed directly to surgical treatment. A retrospective review of all breast cancer patients treated with neoadjuvant chemotherapy between November 2007 and June 2010 was performed. Re-excision rates were calculated for patients who received NACT and were then compared to a group of contemporaneous patients who did not receive neoadjuvant treatment (non-NACT). Re-excisions were routinely performed for disease &lt;2mm from the margin. Patients with DCIS or LCIS were excluded. For statistical analysis, t-test and chi square tests were performed using SAS v9.2. Results: During the study period, 152 patients received neoadjuvant chemotherapy and then underwent surgical treatment of breast cancer. Of these patients, 108 (71.0%) underwent partial mastectomy as primary treatment, 44 (29.0%) underwent mastectomy. As a comparison group, we evaluated 188 consecutive patients diagnosed with invasive breast cancer who underwent initial treatment in the form of partial mastectomy. Table 1 demonstrates the characteristics of NACT and non-NACT patients and margin re-excision rates. Conclusions: Neoadjuvant chemotherapy is often administered in an effort to allow women with larger tumors to pursue breast conservation therapy. This study demonstrates that the rate of margin re-excision in NACT patients is not statistically different from those patients who undergo partial mastectomy as their primary treatment. [Table: see text]

The effect of neoadjuvant Imatinib therapy on outcome and survival after rectal gastrointestinal stromal tumour

The study aimed to characterize the pathological and clinical response of rectal gastrointestinal stromal tumours (GISTs) to neoadjuvant Imatinib. The medical records of patients with rectal GISTs who were diagnosed and treated in five medical centres in Israel between January 2002 and January 2009 were retrospectively examined. Twelve patients who fulfilled the inclusion criteria of nonmetastatic rectal GIST for which preoperative neoadjuvant treatment with Imatinib was considered were suitable for enrollment. Of the 12 patients, nine received neoadjuvant treatment with Imatinib. The three patients who had immediate surgery were excluded. There were five men and four women with a median age of 63 years and a median follow up of 32 months. All tumours were located in the lower two-thirds of the rectum. One patient had a complete clinical response, six had a partial response and two had stable disease. Seven patients subsequently underwent surgery; six had an R0 resection and one had an R1 resection. Three patients had recurrence. There was no disease-related mortality. The reduction in both tumour size and mitotic activity during preoperative Imatinib therapy was significant. Preoperative Imatinib therapy can shrink large rectal GISTs, improving the chances of successful radical surgery and decreasing the risk of considerable morbidity.

Precaution of over or under treatment for colorectal cancer

Insufficient treatment and overtreatment in the management of colorectal cancer greatly influence patients' outcome. The clinicopathological stage of carcinoma located in colon and rectum is different for anatomical differences. The indication of adjuvant chemotherapy varies in colon or rectal cancer. Locally advanced rectal cancer should receive neoadjuvant treatment, however, the optimal regimen is still controversial.

Incorporation of adjuvant therapy into the multimodality management of gastrointestinal stromal tumors of the stomach in the United States.

Gastrointestinal stromal tumors (GIST) treatment changed considerably with introduction of imatinib in 2001 and reports of early successes. However, little is known about imatinib incorporation into practice. Our objective was to examine the integration of adjuvant systemic therapy into GIST management. Patients with gastric GIST were identified (n=4508) from the National Cancer Data Base (2001-2007). Separate regression models were developed to examine factors associated with adjuvant and neoadjuvant therapy use. A total of 3050 patients underwent surgical resection. From 2001-2003 to 2006-2007, use of adjuvant therapy increased from 29 to 47% (P<0.001). Patients were less likely to receive adjuvant therapy if tumors were <3cm, low grade, had negative margins, were treated at low-volume centers, or were diagnosed during 2001-2003 (P<0.01). Adjuvant systemic therapy for lesions <3cm also increased (17 to 25%, P=0.001). For high-risk GISTs, adjuvant therapy use increased from 41 to 58% overall, with increases of 46 to 70% at high-volume centers and 40 to 48% at low-volume centers (P<0.001). Neoadjuvant therapy increased from 0 to 8%; patients were more likely to receive neoadjuvant treatment if their tumor was >6cm, treated at high-volume centers, or were diagnosed during 2006-2007 (P<0.001). Adjuvant systemic therapy use for GISTs was increasing and widespread prior to FDA approval of adjuvant imatinib, suggesting that contemporaneous advances in management of advanced GIST were being simultaneously and rapidly translated into the adjuvant setting. As relatively costly therapies are integrated into practice, more robust tracking systems are needed to monitor the incorporation of new treatments.

Prognostic significance of Ki-67 in node-negative (pN0), triple-negative (TN) breast cancer (BC).

1056 Background: TNBCs occur more frequently in younger women, tend to relapse and metastasize early and have a poor prognosis. They are associated with a range of adverse features including high Ki-67 values. The aim of this analysis was to investigate if Ki-67 could help to identify different prognostic subgroups within the primary pN0 TNBCs. Methods: Patients (pts) with pN0 BC and with ER negative (0%), PgR negative (0%), HER2 scores of 0 and/or FISH not amplified were identified through the institutional clinical database. All pts underwent surgery at the European Institute of Oncology, Milan, Italy, between January 1997 and December 2005 and did not receive neoadjuvant treatment. The association between Ki-67 and other tumour characteristics was evaluated with the Kruskal-Wallis test. The relationship between Ki-67 and the risk of breast-related deaths was evaluated with a multivariable Cox regression model. Cubic splines were applied to the Cox model to analyze Ki-67 as a continuous variable. Results: We identified 496 consecutive pN0 M0 TNBC pts with a median age of 52 years; 443 pts underwent quadrantectomy (89%), and 425 pts (86%) received adjuvant chemotherapy, mainly classical CMF (n=315/425 pts, 74%). The median Ki-67 was 48% (range 4-95). The median follow up was 6 years (range 0.5 −13). Total deaths and deaths from BC were 52 (10.5%) and 38 (7.7%), respectively. Ki-67 was significantly higher in ductal TNBC when compared to other histological types (p<0.01). Moreover, Ki-67 increased with decreasing age (p<0.01), increasing tumour size (p<0.01) and grade (p<0.01). When analyzing Ki-67 as a continuous variable, the risk of death from BC increased steeply with increasing Ki-67 up to about 35% and remained flat thereafter (adjusted effect of Ki-67 P=0.049; adjusted non-linear effect P=0.021). Accordingly, when dividing pts into lower (≤35%)and higher (>35%) Ki-67 subgroups, the 5−year cumulative incidence of breast related deaths were 2.3% and 9.0%, respectively, with an adjusted HR>35 vs ≤35of 2.5 (95% CI 1.0 – 6.0, p=0.046). Conclusions: Within the group of pts with pN0 TNBC, Ki-67 value was associated with different prognoses. Ki-67 value might be useful in the design of trials of risk-adapted adjuvant therapies.

Evolution of multimodality management of gastrointestinal stromal tumors of the stomach.

94 Background: Gastrointestinal stromal tumor (GIST) treatment has changed considerably with introduction of imatinib in 2001, initiation of ACOSOG adjuvant trial in 2002, and FDA adjuvant approval in 2008. However, little is known about how imatinib has been incorporated over time. Our objective was to examine the evolution of multimodality management of GISTs. Methods: Patients coded specifically as gastric GISTs were identified (n = 4,508; 443 hospitals) from the National Cancer Data Base (2001-2007). Changes over time were assessed with chi-squared test for trend. Separate multivariable regression models were developed to examine factors associated adjuvant and neoadjuvant practices. Results: Gastric GISTs reported to NCDB steadily increased: 463 in 2001 to 831 in 2007. 3,289 underwent resection: 78% partial/wedge, 6% total/near-total, and 14% multivisceral. From 2001 to 2007, use of adjuvant therapy increased from 29% to 47% (p &lt; 0.001), although patients were less likely to get adjuvant therapy if older, tumors &lt; 3cm, low grade, negative margins, or treated at low-volume hospitals (p &lt; 0.01). Adjuvant systemic therapy for lesions &lt; 3 cm also increased (17% to 25%, p = 0.001). For GISTs &gt; 6 cm, use of adjuvant therapy increased from 41% to 49% overall, with increases of 45% to 70% at high-volume centers and of 39% to 48% at low-volume centers (all p &lt; 0.001). Neoadjuvant therapy increased from 0% to 15% (p &lt; 0.001) with patients more likely to receive neoadjuvant treatment if size &gt; 6 cm, treated at high-volume centers, or treated in 2006-2007 (p &lt; 0.001). Multivisceral resections decreased over time (19% to 12%, p &lt; 0.001). The proportion of patients treated at high-volume centers increased slightly over time (22.2% to 26.9%, p = 0.006). Conclusions: Adjuvant systemic therapy use for GISTs was increasing and widespread prior to FDA approval of adjuvant imatinib, suggesting contemporaneous advances in advanced GIST management were being translated into the adjuvant setting more than expected. As relatively costly therapies are integrated into practice, more robust tracking systems are needed to follow and guide the incorporation of new treatments. No significant financial relationships to disclose.

Relationship of statins to clinical presentation and biochemical outcomes after radical prostatectomy in Korean patients

The aim of this study was to determine whether or not statins influence biochemical recurrence (BCR) in Korean patients undergoing surgical treatment for prostate cancer. We reviewed data from 687 men who underwent radical retropubic prostatectomy and who did not receive neoadjuvant treatment. Of these patients, 87 reported the use of preoperative statins at surgery. BCR-free survival was determined after exclusion of 78 patients with lymph node metastases and/or who received immediate adjuvant treatment. Patients on statin therapy were more likely to have a co-morbid disease (P < 0.05). Mean PSA (9.6 vs 13.6 ng ml(-1), P = 0.002) and PSA density (0.27 vs 0.38 ng ml(-1) ml(-1), P<0.001) were significantly lower in patients on statins. However, in the multivariable linear regression model, statin use was not associated with a decrease in PSA. Overall BCR for the entire cohort was not significantly different between the statin and nonstatin groups. On multivariate analysis, positive surgical margin and seminal vesicle invasion were independent risk factors for BCR-free survival, whereas other variables, including statin use, were not significant in predicting the risk of BCR. Patients with positive surgical margin and seminal vesicle invasion had a 2.1- (odds ratio, 2.15; 95% confidence interval, 1.29-3.57; P = 0.003) and 2.2-fold risk (odds ratio, 2.21; 95% confidence interval, 1.25-3.89; P = 0.006) of BCR. Preoperative statin use is not associated with reduced BCR following radical prostatectomy.

An elevated body mass index does not reduce survival after esophagectomy for cancer.

Incidences of esophageal cancer and obesity are both rising in the United States. The aim of this study was to determine the influence of elevated body mass index on outcomes after esophagectomy for cancer. Overall and disease-free survivals in obese (BMI≥30), overweight (BMI 25-29), and normal-weight (BMI 20-24) patients undergoing esophagectomy constituted the study end points. Survivals were calculated by the Kaplan-Meier method, and differences were analyzed by log rank method. The study included 166 obese, 176 overweight, and 148 normal-weight patients. These three groups were similar in terms of demographics and comorbidities, with the exception of younger age (62.5 vs. 66.2 vs. 65.3years, P=0.002), and higher incidence of diabetes (23.5 vs. 11.4 vs. 10.1%, P=0.001) and hiatal hernia (28.3 vs. 14.8 vs. 20.3%, P=0.01) in obese patients. Rates of adenocarcinoma histology were higher in obese patients (90.8 vs. 90.9 vs. 82.5%, P=0.03). Despite similar preoperative stage, obese patients were less likely to receive neoadjuvant treatment (47.6 vs. 54.5 vs. 66.2%, P=0.004). Response to neoadjuvant treatment, type of surgery performed, extent of lymphadenectomy, rate of R0 resections, perioperative complications, and administration of adjuvant chemotherapy were not influenced by BMI. At a median follow-up of 25months, 5-year overall and disease-free survivals were longer in obese patients (respectively, 48, 41, 34%, P=0.01 and 48, 44, 34%, P=0.01). In our experience, an elevated BMI did not reduce overall and disease-free survivals after esophagectomy for cancer.