Neoadjuvant Therapy Group Research Articles

Abstract 4257: The survival prediction after curative resection with adjuvant chemotherapy and neo-adjuvant chemotherapy in locally advance stage by gastric mucosal IL-8 mRNA expression for Thai gastric cancer

Abstract Background: Unlike Japanese gastric cancer, the majority type of Thai gastric cancer caused poor prognosis; especially poorly differentiated, signet ring cell histologic type that is predominant in nearly 70 percent of gastric cancer population. The detection of high mRNA IL-8 expression level independently related to poor prognostic histologic type in our recent study. We aim to study adjuvant or neo-adjuvant chemotherapy, and IL-8 mRNA expression level to predict the survival rate after treatment. Method: The prospective study gastric cancer therapy was conducted in 170 new advances gastric cancer cases. The authors recruited only stage III and IV of 111 cases. Adjuvant chemotherapy was completely administration in 68 patients. For the group of neo-adjuvant therapy, FOLFOX IV regimen and others were administrated in 43 patients who had unresectable tumor and underwent enteric access procedure to before chemotherapy treatment. IL- 8 mRNA expression level was tested before chemotherapy treatment. Chi-square test, log rank test, and Kaplan Meier survival curve were used for qualitative and quantitative data analysis (STATA10.0, USA), and p value<.05 is reported statistically significant. Result: Demographic data was described and divided adjuvant therapy, 68 patients, in to 2 groups by two chemotherapy regimens of 5-Fluouracil (5-FU) based combined with cytotoxic drug. The Age, sex, smoking, drinking, disease stage, histology, tumor position, type of operation, percent of positive node were reported as no statistically significant differences in 2 groups. The total means number of lymph node taken off is 11.96±11.48 and 24.62 ±16.48 nodes, respectively and there is no statistically significant. For the Adjuvant therapy, the overall survival rate in 2 groups is not reach statistical significant difference at 45 months. However, toxicity occurred in Cisplatinum with 5- Fluouracil( Cis-FU) more than FOLFOX IV regimen with clinically significant by anemia and neutropenia those need treatment, but no death related toxicity of chemotherapy. Kaplan Meier of overall survival curve treatment has not demonstrated difference between 2 regimens. However, for the neo-adjuvant therapy group, overall survival has reach 40 months and 75 percent of population is still survived in group of high expression. The patients who had IL-8 expression level Raw RQ more than 100, or log10 more than 2 have trend to have prolong median and overall survival than patient who had low expression, although there is not statistically significant difference. Conclusion: The improvement of treatment result by neo-adjuvant therapy by FOLFOX-IV regimen. The higher IL-8 mRNA expression level of Raw RQ more than 100, or log 10>2 demonstrated in prolong survival in group of neo-adjuvant therapy who response to the treatment. Citation Format: Sirikan Yamada. The survival prediction after curative resection with adjuvant chemotherapy and neo-adjuvant chemotherapy in locally advance stage by gastric mucosal IL-8 mRNA expression for Thai gastric cancer. [abstract]. In: Proceedings of the 105th Annual Meeting of the American Association for Cancer Research; 2014 Apr 5-9; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2014;74(19 Suppl):Abstract nr 4257. doi:10.1158/1538-7445.AM2014-4257

Effects of neoadjuvant chemoradiotherapy on postoperative morbidity and mortality associated with esophageal cancer

We compared the surgical outcomes between 114 patients who did not receive neoadjuvant therapy (group 1) and 92 others who received neoadjuvant chemoradiotherapy (nCRT) (group 2), and assessed the preoperative and surgical factors that influence postoperative morbidity to determine the impact of nCRT on morbidity and mortality after esophagectomy via cervical, right transthoracic, and abdominal approaches. The overall postoperative morbidity rates were 44.7% and 55.4% in groups 1 and 2, respectively (P = 0.13). Rates of anastomotic leak (8.8% vs. 16.3%; P = 0.10), pneumonia (9.6% vs. 13.0%; P = 0.44), recurrent nerve palsy (15.8% vs. 10.9%; P = 0.31), and all other complications did not significantly differ between the groups. Multivariable analysis revealed cervical lymph node dissection (odds ratio [OR], 1.97; 95% confidence interval [CI], 1.01-3.84; P = 0.047) as the sole independent covariate for overall morbidity. Furthermore, a history of cardiovascular disease (OR, 2.90; 95% CI, 1.03-8.24; P = 0.045), the retrosternal reconstruction route (OR, 15.15; 95% CI, 3.56-62.50; P = 0.0002), and a longer surgical duration (OR, 1.01; 95% CI, 1.002-1.02; P = 0.01) were independent covariates for anastomotic leakage, and advanced age (OR, 1.08; 95% CI, 1.01-1.15; P = 0.02) and lower body mass index (OR, 1.16; 95% CI, 1.01-1.33; P = 0.04) were independent covariates for pneumonia. However, whether or not patients received nCRT was irrelevant. We found that nCRT is safe for three-incision esophagectomy and it does not increase the incidence of postoperative morbidity and mortality relative to esophagectomy alone.

Volume of breast tissue excised during breast-conserving surgery in patients undergoing preoperative systemic therapy

We aimed to determine whether clinical examination could adequately ascertain the volume of tissue to be resected during breast-conserving surgery after neoadjuvant therapy. We reviewed the clinical reports of 279 patients with histologically diagnosed invasive breast carcinomas treated with neoadjuvant therapy followed by surgery or with primary surgery alone. We estimated volumes of excised tissues, the volume of the tumor mass and the optimal volume required for excision based on 1 cm of clear margins. The actual excess of resected volume was estimated by calculating the resection ratio measured as the volume of the resected specimen divided by the optimal specimen volume. The study endpoints were to analyze the extent of tissue resection and to ascertain the effect of excess resected tissue on surgical margins in both groups of patients. The median tumor diameter was 2.0 and 1.5 cm in the surgery and neoadjuvant therapy groups, respectively. The median volume of resected mammary tissue was 64.3 cm³ in the primary surgery group and 90.7 cm³ in the neoadjuvant therapy group. The median resection ratios in the primary surgery and neoadjuvant therapy groups were 2.0 and 3.3, respectively (p<0.0001). Surgical margin data were similar in both groups. Comparison of the volume of resected mammary tissues with the tumor diameters showed a positive correlation in the primary surgery group and no correlation in the neoadjuvant therapy group. Surgeons tend to excise large volumes of tissue during breast-conserving surgery after neoadjuvant therapy, thereby resulting in a loss of the correlation between tumor diameter and volume of the excised specimen.

Novel aspects of preoperative chemoradiation therapy improving anti‐tumor immunity in pancreatic cancer

Pancreatic cancer is an aggressive cancer with poor prognosis. Little is known about the immune response in the tumor microenvironment after chemotherapy for initially unresectable tumor. The purpose of this study was to investigate the immunological effects of chemoradiation therapy in the tumor microenvironment of pancreatic adenocarcinoma. Seventeen patients with pancreatic adenocarcinoma with and without preoperative chemoradiation therapy were retrospectively analyzed using immunohistochemical methods for HLA class I heavy chain, CD4(+), CD8(+), CD45RO(+) and Foxp3(+) T cell infiltrations. Seven of the 17 study patients received preoperative chemoradiation therapy. There were no statistically significant differences in the number of CD4(+) and CD8(+) T cell infiltrations in the tumor microenvironment. However, the number of Foxp3(+) T cell infiltrations was significantly lower in the neoadjuvant chemoradiation therapy group. The HLA class I expression status was the same between the two groups. In conclusion, preoperative chemoradiation therapy in pancreatic adenocarcinoma is useful for reducing regulatory T cell levels in combination with its direct cytotoxic effects.

Is neoadjuvant therapy beneficial in clinically staged T2N0 esophageal cancer?

135 Background: The optimal treatment strategy for clinical stage T2N0 (cT2N0) esophageal cancer is poorly defined. The specific aims of this analysis were to determine the impact of neoadjuvant therapy (NAT) in cT2N0 esophageal cancer patients on overall survival, nodal metastasis, staging, and pathological complete responders (pCR) NAT. Methods: We reviewed a retrospective cohort of 27 patients with cT2N0 esophageal cancer at Oregon Health &amp; Science University, an NCI-Designated Cancer Center from 1999 to 2011. All patients were staged pre-operatively using Endoscopic Ultrasound (EUS), CT +/- FDG-PET. Patients were identified into two cohorts: NAT followed by surgery and surgery alone. We compared overall survival between the cohorts using Kaplan-Meier analysis. Results: Eleven patients (41%) received NAT followed by surgery and sixteen patients (59%) underwent surgery alone. Minimal invasive esophagectomy and decreased length of stay (p &lt; 0.05) were associated with the presence of neoadjuvant therapy. The difference in overall survival rate was not statistically significant between NAT and surgery alone groups (p = 0.96). Three of 11 patients (27%) had a pCR and 8 (73%) were partial or non responders after NAT. In the surgery only group, nine of 16 patients (56%) were understaged, 6 (38%) were overstaged and 1 (6%) was correctly staged. Despite being clinically node negative, 14/27 (52%) had node positive disease in both groups with 5/11 (45%) in NAT group and 9/16 (56%) in surgery group. Conclusions: The benefit of NAT in cT2N0 esophageal cancer patients remains unclear. However, our finding of significant clinical understaging and frequent positive nodes in clinically node negative patients suggests a clinical benefit to NAT for some cT2N0 patients before surgery. These observations support design of a prospective clinical trial to define the role of NAT in patients with cT2N0 esophageal cancer.

Effect of multidisciplinary team treatment on outcomes of patients with gastrointestinal malignancy

To evaluate the effect of multidisciplinary team (MDT) treatment modality on outcomes of patients with gastrointestinal malignancy in China. Data about patients with gastric and colorectal cancer treated in our center during the past 10 years were collected and divided into two parts. Part 1 consisted of the data collected from 516 consecutive complicated cases discussed at MDT meetings in Peking University School of Oncology (PKUSO) from December 2005 to July 2009. Part 2 consisted of the data collected from 263 consecutive cases of resectable locally advanced rectal cancer from January 2001 to January 2005. These 263 patients were divided into neoadjuvant therapy (NT) group and control group. Patients in NT group received MDT treatment, namely neoadjuvant therapy + surgery + postoperative adjuvant therapy. Patients in control group underwent direct surgery + postoperative adjuvant therapy. The outcomes in two groups were compared. The treatment strategy was altered after discussed at MDT meeting in 76.81% of gastric cancer patients and in 58.33% of colorectal cancer patients before operation. The sphincter-preservation and local control of tumor were better in NT group than in control group. The 5-year overall survival rate was also higher in NT group than in control group (77.23% vs 69.75%, P = 0.049). MDT treatment modality can significantly improve the outcomes of patients with gastrointestinal malignancy in China.

Neoadjuvant hormonal therapy does not impact the treatment success of high-intensity focused ultrasound for the treatment of localized prostate cancer

To assess the potential efficacy of the effects of neoadjuvant hormonal therapy on high-intensity focused ultrasound (HIFU) in the treatment of localized prostate cancer. One hundred seventy patients with localized prostate cancer underwent HIFU of the prostate, of which 114 patients, who met the study criteria, were included in the current study. The primary outcome was prostate-specific antigen (PSA) changes, and the secondary outcome was morbidity. Biochemical failure was defined according to the Phoenix criteria (prostate-specific antigen nadir +2 ng/ml). The median follow-up period for all patients was 45.0 months (range: 12-70). All patients underwent PSA evaluation, and 52 (56.5%) had a 2-month PSA nadir recorded at the follow-up visit. PSA nadir was achieved by 3 months in 84.2% of treatments. The mean PSA nadir was 0.28 ng/ml. The 114 patients consisted of two groups: 44 patients treated with neoadjuvant hormonal therapy (group 1), and 70 patients treated without neoadjuvant hormonal therapy (group 2). The mean PSA nadir achieved in group 1 was 0.19 ng/ml versus 0.34 ng/ml in group 2 (n.s.). The occurrence rates of treatment-related toxicities were similar in both groups. In patients with localized prostate cancer, HIFU therapy resulted in comparable immediate cancer control. The present results indicate that combined treatment using hormonal therapy and HIFU does not have a synergistic effect on the PSA nadir.

Abstract P1-01-05: Clinical Significance of Tumor Burden in the Sentinel Nodes after Neoadjuvant Therapy Differs from Sentinel Nodes in the Adjuvant Setting and This May Influence the Management of the Axilla

Abstract Background. Lymph node metastases are the most significant prognostic factor for breast cancer patients. The use of sentinel node biopsy (SLN) has generated an increased detection of positive nodes through the identification of isolated tumor cells (ITC) and micrometastasis. The objective of this study is to evaluate the significance of SLN micrometastasis and ITC for patients undergoing neoadjuvant chemotherapy versus patients undergoing surgery first. Material and Methods. A total of 571 patients with clinically node negative T1-T3 breast cancer underwent SLN surgery from 2004 to 2008. Clinicopathological data were reviewed and comparison was made between results in the adjuvant and neoadjuvant setting. Results. Of the 571 patients, 71 patients (12.5%) underwent SLN biopsy after neoadjuvant chemotherapy and 500 (87.5%) underwent surgery first. The SLN identification rate in the adjuvant and neoadjuvant therapy groups were similar (96.2% vs 95.8%). Mean number of sentinel nodes removed were 2,2 (range 1-15) in the adjuvant group and 2.2 (range 1-7) in the neoadjuvant group. The SLN was positive in the adjuvant group in 151 patients (30%) while in 27 patients (37.5%) in the neoadjuvant group. The SLN was the only positive node in 106 patients (70.1%) in the adjuvant group and in 6(26%) in the neoadjuvant group. Micrometastasis in the SLN was found in 39 patients (7.8%) in the adjuvant group and in 7 (9.8%) patients in the neoadjuvant group. In the adjuvant group, 7 patients (17.9%) had additional non SLN positive in the axillary dissection (ALND), while 3 (49%) in the neoadjuvant group. ALND was performed in all patients with ITC in the SLN in the neoadjuvant setting and 50% of them had additional nonSLN. Discussion. The significance of micrometastasis or ITC in the sentinel node seems to differ in patients with neoadjuvant therapy or surgery first. Micrometastsis or ITC in patients with prior neoadjuvant therapy may reflect residual disease in the axilla, as 50% of patients will have additional positive nodes. Completion axillary node dissection should be considered in this group of patients. Even more, the majority of patients with a positive SLN in the neoadjuvant group harbored additional positive axillary nodes. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P1-01-05.

Abstract P2-06-07: Estrogen Receptor Beta as a Coadjuvant Target? A Short-Time Prospective Double Blind Study

Abstract Background: The role of estrogen receptor beta (ER-b) in human breast cancer remains unclear. There is no consensus regarding the clinical utility of an ER-b assay. Some studies have suggested that ER-b may oppose actions of estrogen receptor alpha (ER-a) in breast cancer cells and clinical evidences indicate that loss of ER-b expression is associated with a poor prognosis and resistance to endocrine therapy. Tumor expression of the Ki67 antigen is used to assess the prognosis of cancer patients. A change in the expression of Ki67 after short-term exposure of patients to therapeutic agents is frequently used as a proliferation marker of treatment efficacy. The association between ER-b and HER-2, the human epidermal growth factor receptor 2 used in the clinical setting as a prognostic and predictive marker, in breast tumors remains unclear. Objectives: The aim of this study was to compare the expression of Ki-67, HER-2, ER-a and ER-b in postmenopausal women with invasive ductal carcinomas (IDC), prior and after tamoxifen and anastrozole in neoadjuvant short-time treatment. Material and Methods: Patients were double-blind randomized in a prospective placebo controlled study with three neoadjuvant hormone therapy (HT) groups. To determine the clinical significance of the tumor cell proliferation during endocrine therapy for breast cancer, we measured the expression of Ki67 in tumor biopsy samples taken before and after 26 days of presurgical treatment with anastrozole 1mg/day (n= 25) or tamoxifen 20mg/day (n= 24) or placebo (n=29) in 78 patients with primary palpable IDC (stage II and III). Pre and post HT samples were disposed in tissue micro array blocks and submitted to immunohistochemical essay. Biomarkers status (Ki-67, HER-2, ER-a and ER-b) were obtained comparing each immunohistochemical evaluation of pre and post-surgery samples using semi-quantitative Allred's method. Statistical analysis were performed using the GEE (General Estimation Equations) and Anova tests with significant p &amp;lt; 0,05. Results: Randomization was adequate. HER2 did not show any variation in the three groups evaluated. With positive ER-b (Allred's score 3 to 8), only anastrozole group showed a significant reduction in KI-67 status from 4.46 in the pre-treatment to 3.15 in post treatment samples (p=0.0130). Positive ER-a breast cancers showed a significant reduction in KI-67 status in tamoxifen and anastrozole groups, and this reduction was correlated to a positive ER-b score. Discussion: Clinical management of breast cancer is guided by assessment of some tumor parameters. One of these is estrogen receptor status. With the discovery of ER-b, definition of ER status is potentially more complex. Our study brings new data about the short-time exposure to endocrine therapy. The role of ER-a may be different when co-expressed with ER-b and ER-b signaling may be a therapeutic target in these tumors. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P2-06-07.

In an era of health reform: Defining cost differences in current esophageal cancer management strategies and assessing the cost of complications

Outcomes assessing various treatment modalities for esophageal cancer primarily report results in terms of morbidity, mortality, survival, and quality of life. The most appropriate stage-by-stage treatment for esophageal cancer remains controversial. There are limited data outlining the comparative costs of surgical, combined modality and definitive chemoradiation treatments, and added costs associated with complications. Between 2000 and 2004, 4 treatment groups were studied: surgery alone, chemotherapy followed by surgery, chemoradiotherapy followed by surgery, and chemoradiotherapy alone. Fifteen consecutive patients from each group receiving their entire treatment at Virginia Mason Medical Center were identified. Patient demographics and outcomes were taken from a prospective institutional review board-approved surgical database, and chart review obtained information for neoadjuvant therapy and definitive chemoradiotherapy groups. Treatment-related costs were extracted from Virginia Mason Medical Center's financial data management system between date of diagnosis to 90 days after completion of primary therapy. Treatment groups were similar in age, gender ratio, American Society of Anesthesiologists status, body mass index, and tumor cell type. Costs increased with the number of treatment modalities: surgery alone, $33,517; chemotherapy followed by surgery, $41,875; chemoradiotherapy followed by surgery, $47,389; and chemoradiotherapy alone, $46,659. Treatment-related complications were surgery alone, 47%; chemotherapy followed by surgery, 64%; chemoradiotherapy followed by surgery, 66%; and chemoradiotherapy alone, 87% (P = .139). Complications increased costs in all groups: surgery alone, 26% (P = .008); chemotherapy followed by surgery, 23% (P = .001); chemoradiotherapy followed by surgery, 9% (P = .702); and chemoradiotherapy alone, 19% (P = .248). Costs vary significantly among treatment approaches: surgery alone costs 80% of chemotherapy and surgery, 71% of chemoradiotherapy and surgery, and 72% of chemoradiotherapy alone. Costs of tri-modality therapy and definitive chemoradiotherapy are similar. Especially in the absence of definitive evidence-based data, these costs should be a factor in the production of future national treatment guidelines. Decreasing costs requires future quality initiatives in esophageal cancer treatment that focus on minimizing complications related to treatment.

Clinical significance of lymphovascular invasion in rectal cancer following neoadjuvant therapy

Objective To investigate lymphovascular invasion (LVI) in mid-low rectal cancer following neoadjuvant therapy. Methods A total of 297 consecutive patients with mid-low rectal cancer received radical surgery from August 2002 to August 2005 at Beijing Cancer Hospital. All patients were divided into the neoadjuvant therapy group and a control group according to whether they underwent preoperative radiotherapy or radiochemotherapy. Histological assessment of tumor specimens was made, and correlation of LVI and prognosis was analysed using the chi-square test. The disease-free survival rate and overall survival rate were analysed by the Kaplan-Meier survival curve. Results The overall positive rate of LVI was 23.9% (71/297). The positive rates of LVI in neoadjuvant therapy group and control group were 21.5% (31/144) and 26. 1% (40/153), respectively,with no significant difference between the groups ( x2 = 0.872, P ＞ 0.05). In the neoadjuvant therapy and control groups, LVI was significantly associated with pathologic T and N stages as well as the degree of histological differentiation (x2 =13.490, 27.401,7.323;16. 188, 21.623, 16.534, P＜0.05). In the control group, LVI was closely associated with local recurrence (x2 =4. 010, P ＜0.05 ), whereas this was not the case in the neoadjuvant therapy group (x2 =0.000, P＞0.05). LVI was significantly associated with distal metastasis in both the neoadjuvant therapy and control groups (x2 = 4.950, 14. 332, P ＜ 0.05 ). The disease-free and overall survival rates of patients with LVI were 46.4% (26/56) and 56.7% (34/60), which were significantly lower than 75.1%(148/197) and 79.4% ( 166/209 ) of those with no LVI, respectively ( x2 = 16. 720, 12.660, P ＜ 0.05 ).Conclusions Neoadjuvant therapy does not significantly reduce LVI;however, the biological behaviour of LVI has changed. Patients with LVI may benefit from neoadjuvant radiotherapy. Key words: Neoadjuvant therapy; Rectal neoplasms; Lymphovascular invasion

A Novel Histopathological Evaluation Method Predicting the Outcome of Non-small Cell Lung Cancer Treated by Neoadjuvant Therapy: The Prognostic Importance of the Area of Residual Tumor

Histopathological evaluation method for predicting the outcome of non-small cell lung cancer (NSCLC) treated by neoadjuvant therapy has not been fully assessed. The purpose of this study was to assess a novel histopathological evaluation method for predicting the outcome of NSCLC treated by neoadjuvant therapy. We reviewed the histopathology of the tumors of 53 NSCLC treated by neoadjuvant chemotherapy, chemoradiotherapy, or radiotherapy followed by complete resection and identified the histologic features produced by neoadjuvant therapy by comparing them with the histologic features of the tumors in 138 NSCLC cases treated by surgery without neoadjuvant therapy. We also measured the area of residual tumor (ART) on the maximum cut surface of the tumors and analyzed the relationships between the histologic features, ART, and the outcome. The proportions of cases with the histologic features "cholesterin clefts," "foreign body reactive giant cells," "stromal hyalinosis," and "bizarre nucleus in more than 50% of the cancer cells" were significantly higher in the neoadjuvant therapy group than in the surgery alone group. However, the presence of none of these features had any significant effect on survival. Although pathologic T factor and N factor had no significant effect on overall survival, smaller ART (< or =400 mm) and absence of pleural invasion (p [-]) were predictors of a outcome (p = 0.014 and p = 0.003, respectively). Smaller ART and p (-) predict a better outcome of NSCLC treated by neoadjuvant therapy. We concluded that ART is a novel histopathological evaluation method for predicting the outcome of NSCLC treated by neoadjuvant therapy.

The effect of neoadjuvant therapy on the 5-fluorouracil metabolic and relative enzymes of oral squamous cell carcinoma

To assess the effect of neoadjuvant therapy using tegafur/uracil (UFT) and radiation therapy on the 5-fluorouracil (5-FU) metabolic and relative enzymes, thymidylate synthase (TS), dihydropyrimidine dehydrogenase (DPD), orotate phosphoribosyl transferase (OPRT) and thymidine phosphorylase (TP) in oral squamous cell carcinoma (OSCC), we examined the mRNA expression and immunohistochemical staining status of these enzymes using 17 surgical specimens. Seven patients did not receive any neoadjuvant therapy and 10 were treated with UFT and local irradiation therapy. Our result showed that the mRNA expression of these enzymes in neoadjuvant group was not significantly different from that of non-treated group using real-time quantitative PCR. To confirm the protein expression, we also carried out immunohistological staining of TS and DPD two key enzymes in the 5-FU metabolism, using the same specimens. Immunohistological staining status did not correspond to the results of mRNA analysis completely, though no significant difference between the groups was observed. Furthermore, no significant relationship between the UFT administration period and mRNA expression of the 5-FU metabolic enzymes was observed in neoadjuvant therapy group and also the distribution of the enzyme mRNA expression levels was similar to that of non-treated group. The results suggested that the neoadjuvant therapy of OSCC might not affect the expression status of 5-FU metabolic and relative enzymes in surgical tumor samples and the tumor tissues might serve as a useful specimen source to analyze the expression status of the 5-FU metabolic and relative enzymes and to determine the prospective efficiency of 5-FU-based adjuvant chemotherapy.

A novel histopathological evaluation method for predicting the outcome of non-small cell lung cancer treated by neoadjuvant therapy

e11574 Background: Chemotherapy, chemoradiotherapy, or radiotherapy is sometimes used to treat non-small cell lung cancer (NSCLC) before surgical resection (neoadjuvant therapy). However, no histopathological evaluation method for predicting the outcome of NSCLC treated by neoadjuvant therapy has been fully assessed. The purpose of this study was to assess a novel histopathological evaluation method for predicting the outcome of NSCLC patients who received neoadjuvant therapy followed by surgical resection. Methods: We reviewed the histopathology of the tumors of 61 NSCLC patients who received neoadjuvant chemotherapy, chemoradiotherapy, or radiotherapy and identified the histological features produced by neoadjuvant therapy by comparing them with the histopathological features of the tumors in 138 NSCLC cases treated by surgery without neoadjuvant therapy. We also measured the area of residual tumor (ART) on the maximum cut surface of the tumors and analyzed the relationships between the histological features, ART, and the outcome. Results: The proportions of cases with the histological features “cholesterin clefts,” “foreign body reactive giant cells,” “stromal hyalinosis,” and “cancer cells more than 50% of which contained a bizarre nucleus” were significantly higher in the neoadjuvant therapy group than in the surgery alone group. However, the presence of none of these features except “stromal hyalinosis” had any significant effect on survival in the neoadjuvant therapy group. Although pathological T factor (ypT) and N factor (ypN) had no significant effect on overall survival, smaller ART (≤400 mm2) and absence of pleural invasion (p(-)) were predictors of a outcome (p=0.004 and p=0.001, respectively). Conclusions: Smaller ART (≤400 mm2) and p(-) predict a better outcome of NSCLC in patients who receive neoadjuvant therapy. We concluded that ART is a novel histopathological parameter for predicting the outcome of NSCLC patients who receive neoadjuvant therapy followed by surgical resection. No significant financial relationships to disclose.

Lymph Node Harvest After Proctectomy for Invasive Rectal Adenocarcinoma Following Neoadjuvant Therapy

Recent reports indicate that neoadjuvant therapy significantly reduces the lymph node harvest of rectal cancer. The aim of this study was to interpret the lymph node harvest in this setting based on the primary tumor response. All patients undergoing proctectomy were included. Three variables were used as indicators of primary tumor response: ypT stage, tumor size, and tumor regression grade. From 1998 to 2007, 237 patients were identified: 157 in the neoadjuvant therapy group and 80 in the nonneoadjuvant therapy group. Neoadjuvant therapy significantly reduced the number of lymph nodes harvested (P = 0.011). Compared with the nonneoadjuvant group, there were significantly fewer lymph nodes in the neoadjuvant early T stage group (P = 0.001), small tumor size group (P = 0.003), and low tumor regression grade group (P < 0.001). However, there was no significant difference between the nonneoadjuvant group and the neoadjuvant advanced T stage (P = 0.664), large tumor (P = 0.815), and high tumor regression grade groups (P = 0.566). The current standard of lymph node harvest should be applied to patients with poorly responding primary tumors after neoadjuvant therapy. However, a new standard may be necessary to define the adequate number of lymph nodes for tumors that respond well to neoadjuvant therapy.

Neoadjuvant hormonal deprivation for patients undergoing radical prostatectomy

The purpose of this study is to evaluate the therapeutic effect of radical prostatectomy combined with preoperative neoadjuvant hormonal ablation therapy for prostate cancer (PCa). In this study, a total of 31 patients with local PCa underwent radical prostatectomy; of these, 12 patients underwent preoperative hormonal deprivation with a combination of goserelin and flutamide for a period of 5.6 months. Data regarding clinical characteristics were compared between the neoadjuvant therapy and radical prostatectomy groups. A total of 31 patients received pelvic lymph node clearance, and the rate of positive lymph nodes was 12.9% (4/31). Serum prostate-specific antigen (PSA) was 8.9 +/- 1.2 microg L(-1) after the neoadjuvant therapy and 0.4 +/- 0.3 microg L(-1) one month after the radical prostatectomy. There were significant differences in the positive surgical margins, seminal vesicle invasion and lymph node metastasis between the neoadjuvant therapy group (n = 12) and the radical prostatectomy group (n = 19, P < 0.01). The resulsts indicates that preoperative hormonal deprivation induced by goserelin and flutamide can decrease clinical and pathological staging, but assessment of its influence on long-term prognosis requires further study.

Impact of neoadjuvant chemoradiotherapy on functional outcomes for patients with uT3 rectal cancer undergoing restorative resection

4098 Background: Our aim is to determine whether neoadjuvant chemoradiation adversely affects functional outcomes for patients with ultrasound stage T3 (uT3) middle and lower third rectal cancer undergoing surgery. Methods: All patients with uT3 middle and lower third rectal cancers who underwent surgery from 1986–2007 were identified from a prospectively maintained cancer database. Prospectively accrued functional outcomes for patients who had neoadjuvant therapy (Group A) were compared with those for patients who did not (Group B). Quality of life (QOL) was measured using SF 36. Results: There were 297 patients in Group A and 153 in group B. Complete response rate was 16.6%. Group A had more males(76 vs 65%, p=0.02) and were younger (59±11.9 vs 66.5 ±12.2 yrs, p<0.001). Group A also had lower tumor distance from anal verge(5.5±2.4 vs 6.2±2.3 cm, p=0.004), greater use of hand-sewn anastomoses (29.9% versus 12.0%, p=0.002) and proximal diversion(38.2% vs19.2%, p<0.001). Tumor differentiation was similar in both groups. Group B had larger tumors (4.5±1.8 vs 2.6±1.7, p=<0.001) with more involved lymph nodes (1, 0–52; 0, 0–22, p=<0.001). Anastomotic leak rate was similar(Grp A: 4 vs 6.8%, p=0.27). Group A had lower local recurrence (12.6% vs. 24.4%, p<0.001) and greater disease free survival rate(75.7% vs. 51.9%, p<0.001). Long term functional outcome were measured by number of day and night time bowel movements, control of solid, liquid and gas and pad use. After adjusting for age, gender, complication and reservoir use, at the time of their most recent evaluation, functional outcomes for patients undergoing restorative resection (Grp A 67.8%, Grp B53.5%) were comparable between groups. Despite the greater proportion of patients with a permanent stoma in Group B, QOL was similar between groups. Conclusion: For uT3 cancer of the mid and lower rectum, neoadjuvant therapy is associated with better oncologic outcomes. With careful surgical technique and judicious use of a reservoir, chemoradiation prior to surgery does not appear to adversely influence functional outcomes. The presence of a permanent stoma does not seem to influence QOL. No significant financial relationships to disclose.

Frequency and number of neuroendocrine tumor cells in prostate cancer: No difference between radical prostatectomy specimens from patients with and without neoadjuvant hormonal therapy

Neuroendocrine tumor cells in prostate cancer are thought to increase after hormonal therapy due to neuroendocrine differentiation of tumor cells. This assumption is based on the histological analyses of limited portions of the cancerous lesions examined. Radical prostatectomy specimens were obtained from 122 consecutive patients with prostate adenocarcinoma, 70 of whom underwent prostatectomy alone (Group A) and 52 with neoadjuvant hormonal therapy (Group B). Sections from all the 5-mm-thick slices from formalin-fixed specimens were immunostained for chromogranin-A, and the total number of choromogranin-A-positive neuroendocrine tumor cells were counted. No difference was found between Groups A and B in the frequency of cancer with neuroendocrine cells. The total number of neuroendocrine cells in cancer varied widely with no difference of median values in the two groups. These results do not support the assumption that hormonal therapy induces neuroendocrine differentiation, but suggest androgen-independent neuroendocrine cells existed before therapy.

Neoadjuvant Therapy for Rectal Cancer Down-Stages the Tumor but Reduces Lymph Node Harvest Significantly

The impact of neoadjuvant therapy (NAT) for rectal cancer on lymph node yield is not well known. This study evaluates the impact of NAT on tumor regression and lymph node harvest. The subjects were 40 patients with rectal cancer; 20 receiving high-dose, long-course neoadjuvant therapy, and 20 age- and sex-matched controls who did not receive neoadjuvant therapy. Tumor regression (TRG) was graded from 1 to 5 as: TRG1, no residual tumor cells; TRG2, occasional residual tumor cells with marked fibrosis; TRG3, marked fibrosis with scattered tumor cells or groups; TRG4, abundant cancer cells with little fibrosis; TRG5, no tumor regression. We also evaluated the number of lymph nodes retrieved from excised specimens, the size of the largest node, and the extent of lymph node involvement by the tumor. Tumor regression was seen in all patients; as TRG1 in 6 (30%), TRG2 in 2 (10%), TRG3 in 3 (15%), and TRG4 in 9 (45%). The median nodal harvest was 4 (range (0-12) in the NAT group vs 9 (range 1-19) in the control (P = 0.001). The median size of the largest lymph node was 5 mm (range 2-12 mm) in the NAT group vs 9 mm (range 4-15 mm) in the control group (P = 0.004). Tumor-positive nodes were identified in 4 of 17 of the NAT group patients and in 9 of the 20 controls (P = 0.308). Although NAT down-stages rectal cancer, it results in a significantly low yield of lymph nodes, which are also significantly smaller than those in nonirradiated controls. Therefore, surgeons and histopathologists must ensure adequate sampling and accurate staging is done for patients with irradiated rectal cancer.

Evaluation of quality of life of patients with oral squamous cell carcinoma. Comparison of two treatment protocols in a prospective study

Background and purpose In recent years, various therapeutic concepts have been developed for treating oral cancer, these include preoperative simultaneous ‘neoadjuvant’ radio-chemotherapy and one-stage-surgery with tumour ablation and reconstruction. When considering long-term survival, there is substantial evidence that the neoadjuvant therapy is superior to the primary surgical approach with postoperative radiation. Both treatment concepts, however, have a strong impact on the quality of life. Patients and methods This study prospectively evaluates and compares quality of life in 53 patients with oral cancer treated according to a neoadjuvant concept or primarily surgically, using the questionnaires QLQ C-30 and H and N35 by the EORTC. Results Initially both groups showed a marked reduction in the quality of life. Despite a clear improvement in the first postoperative year baseline values were not reached in most of the scores. Specific long-lasting impairments in the symptom scales concerning oral functions were found in both treatment arms. In the neoadjuvant therapy group, however, especially global health and the emotional status were reduced to a higher degree than in the other group. This was particularly noticeable in the early treatment phase. Conclusions Following an initial deterioration of quality-of-life after 3 months a gradual improvement of physical and psychological function was observed in the course of the first post-treatment year in both groups. Severe side effects can be observed. These side effects vary strongly in their individual expression. Limitations in the quality of life can be justified, if the more aggressive therapy resulted in a better disease free survival.