Adjuvant Chemotherapy Group Research Articles

PD-L1 expression and TOP3A mutation as prognostic factors for adjuvant chemotherapy in triple negative breast cancer.

541 Background: Triple negative breast cancer (TNBC) is a highly aggressive subtype of breast cancer that is markedly heterogeneous and lacks specific targets. The aim of this study is to explore potential predictors and therapeutic targets based on clinical and genetic characteristics. Methods: 138 patients with triple-negative breast cancer after surgical treatment were 1:1 randomly assigned to the paclitaxel combined with carboplatin (TCb) group or the epirubicin combined with cyclophosphamide sequential paclitaxel (EC-T) adjuvant chemotherapy group. PD-L1 was retrospectively analyzed by surgically resected specimens, and 733 cancer-related genes were detected by NGS. Pathway enrichment analysis was performed using DAVID for functional enrichment genetic alterations. Cox regression models and Kaplan-Meier were used to evaluate disease-free survival (DFS). Results: In this study, there was no significant difference in DFS between the TCb and EC-T groups. 31 (22.5%) of 138 TNBC patients were positive for PD-L1 expression, including 15 (10.9%) patients positive for PD-L1 in tumor cells (TCs) and 29 (21.0%) patients positive for PD-L1 in tumor-infiltrating immune cells (TICs). Patients with positive PD-L1 expression, either in TCs or TICs, achieved better DFS [HR=0.13 (95% CI: 0.02-0.93), p=0.016], the difference was also shown in the EC-T group [HR=0 (95% CI: 0- inf), p=0.037], but not in the TCb group [HR=0 (95% CI: 0.04-2.1), p=0.189]. In addition, we identified 7 patients with mutations in DNA topoisomerase IIIα(TOP3A), a homologous recombination (HR)-related gene, and patients with mutations in this gene had worse DFS than those without mutations [HR=4]. However, there was no statistically significant association between BRCA mutation and response to either therapeutic regimens. Conclusions: In this TNBC patient population, immunohistochemistry (IHC) and NGS analyses identified potential prognostic markers. PD-L1 positive and TOP3A mutation were significantly associated with early triple-negative breast cancer prognosis.

Role of surgery in a case-control study of patients with clinical stage IIIA small cell lung cancer.

BackgroundThe role of surgery in the multidisciplinary treatment of clinical stage IIIA small cell lung cancer is yet to be verified. This study was performed to determine the benefit of surgery in patients with stage IIIA small cell lung cancer.MethodsPatients diagnosed with stage IIIA small cell lung cancer at Shanghai Pulmonary Hospital from 2005 to 2015 were included and divided into two groups: the surgery with neoadjuvant and adjuvant chemotherapy group and the concurrent chemo-radiotherapy group. Overall survival was compared between the two groups. A multivariate Cox regression model was constructed to evaluate factors associated with overall survival.ResultsOf 69 patients with stage IIIA small cell lung cancer during the study period, 40 patients (58%) underwent surgery with neoadjuvant and adjuvant chemotherapy, and 29 patients (42%) underwent concurrent chemo-radiotherapy. Patients in the surgery with neoadjuvant and adjuvant chemotherapy group had a longer overall survival compared with patients in the concurrent chemo-radiotherapy group (median survival: 33.1 vs. 16.2 months, respectively; 2-year overall survival: 44.2% vs. 14.9%, respectively; log-rank: P=0.045). A multivariate analysis revealed that surgery with neoadjuvant and adjuvant chemotherapy (hazard ratio: 0.374; 95% confidence interval: 0.173–0.808, P=0.012) was independently associated with overall survival.ConclusionsPatients with stage IIIA small cell lung cancer treated with surgical resection plus chemotherapy demonstrated longer overall survival compared with those who underwent concurrent chemo-radiotherapy. Surgery may be an option for clinical stage IIIA small cell lung cancer after induction chemotherapy in selected patients.

Novel candidate factors predicting the effect of S-1 adjuvant chemotherapy of pancreatic cancer

The collagen gel droplet-embedded drug sensitivity test (CD-DST) was revealed to be useful for predicting the effect of S-1 adjuvant chemotherapy for pancreatic ductal adenocarcinoma (PDAC). However, collection of an adequate number of PDAC cells is difficult due to the surrounding fibroblasts. Thus, the aim of this study was to discover novel biomarkers to predict chemosensitivity based on the CD-DST results. Proteomics analysis was performed using liquid chromatography tandem mass spectrometry (LC–MS/MS). Candidate proteins were validated in patients with 5-FU CD-DST results via immunohistochemistry (IHC). The relationships between the candidate proteins and the effect of the adjuvant S-1 were investigated via IHC. Among the 2696 proteins extracted by LC–MS/MS, C1TC and SAHH could accurately predict the CD-DST results. Recurrence-free survival (RFS) was significantly improved in the IHC-positive group compared with the IHC-negative group in both factors. The negative group did not show a significant difference from the group that did not receive S-1. The double-positive group was associated with significantly prolonged RFS compared to the no adjuvant chemotherapy group. C1TC and SAHH have been shown to be useful biomarkers for predicting 5-FU sensitivity as a substitute for the CD-DST in adjuvant chemotherapy for PDAC.

Safety and effectiveness of oxaliplatin combined with capecitabine or oxaliplatin combined with S-1 neoadjuvant chemotherapy in the treatment of advanced gastric cancer

Objective: To explore the safety and efficacy of oxaliplatin plus capecitabine (CapeOX) or oxaliplatin plus S-1 (SOX) regimen neoadjuvant chemotherapy in the treatment of advanced gastric cancer. Methods: A retrospective cohort study was performed. Clinical data of patients diagnosed as advanced gastric cancer undergoing CapeOX/SOX neoadjuvant chemotherapy and standard laparoscopic radical operation for gastric cancer in Ruijin Hospital of Shanghai Jiaotong University School of Medicine from April 2016 to April 2019 were retrospectively collected. Inclusion criteria were as follows: (1) age≥18 years; (2) gastric adenocarcinoma was confirmed by histopathology and the clinical stage was T3-4aN+M0; (3) tumor could be resectable; (4) preoperative neoadjuvant chemotherapy was CapeOX or SOX regimen without radiotherapy or other regimen chemotherapy; (5) no other concurrent malignant tumor; (6) the Eastern Cooperative Oncology Group (ECOG) score ≤ 1; (7) no bone marrow suppression; (8) normal liver and kidney function. Exclusion criteria were as follows: (1) patients with recurrent gastric cancer; (2) patients receiving emergency surgery due to tumor perforation, bleeding, obstruction, etc.; (3) allergy to oxaliplatin, S-1, capecitabine or any drug excipients; (4) diagnosed with coronary heart disease, cardiomyopathy, or the New York Heart Association class III or IV; (5) pregnant or lactating women. A total of 118 patients were enrolled as the neoadjuvant chemotherapy group, and 379 patients with locally advanced gastric cancer who received surgery combined with postoperative adjuvant chemotherapy over the same period simultaneously were included as the adjuvant chemotherapy group. After propensity score matching was performed including gender, age, ECOG score, tumor site, clinical stage, chemotherapy regimen and other factors by 1:1 ratio, there were 40 cases in each group. The differences between the two groups in general conditions, efficacy of neoadjuvant chemotherapy, intraoperative conditions, postoperative conditions, histopathological results, chemotherapy-related adverse events, and survival status were compared and analyzed. Results: Comparison of baseline demographics between the two groups showed no statistically significant difference (all P>0.05). In the neoadjuvant chemotherapy group, 5.0% (2/40) of patients achieved clinical complete response, 57.5% (23/40) achieved partial response, 32.5% (13/40) remained stable disease, and 5.0% (2/40) had disease progression before surgery. Objective response rate was 62.5% (25/40), and disease control rate was 95.0% (38/40). There were no statistically significant differences between neoadjuvant chemotherapy group and adjuvant chemotherapy group in terms of operation time, intraoperative blood loss, number of lymph node harvested, length of postoperative hospital stay, and postoperative mortality and morbidity (all P>0.05). Postoperative complications were well managed with conservative treatment. No Clavien-Dindo IV or V complications were observed in both groups. Pathological results showed that the proportion of patients with pathological stage T1 in the neoadjuvant chemotherapy group was significantly higher than that in the adjuvant chemotherapy group [27.5% (11/40) vs. 5.0% (2/40)], while the proportion of patients with pathological stage T3 was significantly lower than that in the adjuvant chemotherapy group [20.0% (8/40) vs. 45.0% (18/40)], with statistically significant difference (χ(2)=15.432, P=0.001). In the neoadjuvant chemotherapy group, there were 4 cases of tumor regression grade 0, 8 cases of grade 1, 16 cases of grade 2, and 12 cases of grade 3. The pathological complete response rate was 10% (4/40), the overall pathological response rate was 70.0% (28/40). There was no statistically significant difference in the incidence of chemotherapy-related adverse events between neoadjuvant chemotherapy group and adjuvant chemotherapy group [40% (16/40) vs. 37.5% (15/40), P>0.05). There were no statistically significant differences in OS (43 months vs. 40 months) and 3-year OS rate (66.1% vs. 59.8%) between neoadjuvant chemotherapy group and adjuvant chemotherapy group (P=0.428). The disease-free survival (DFS) and 3-year DFS rates of the neoadjuvant chemotherapy group were significantly superior to those of the adjuvant chemotherapy group (36 months vs. 28 months, 51.4% vs. 35.8%, P=0.048). Conclusion: CapeOX or SOX regimen neoadjuvant chemotherapy is a safe, effective and feasible treatment mode for advanced gastric cancer without increasing surgical risk and can improve the DFS of patients.

The role of adjuvant chemotherapy in esophageal cancer patients after neoadjuvant chemotherapy plus surgery.

Esophageal cancer typically has a poor prognosis. While neoadjuvant chemotherapy (NAC) is reported to be effective for esophageal cancer patients, the prognosis of patients for whom NAC is ineffective remains poor. In total, 113 patients with thoracic esophageal squamous cell carcinoma who were treated between January 2006 and December 2015 were enrolled. These patients received NAC followed by radical surgery and had three or more pathologic positive lymph nodes. The effectiveness and feasibility of adjuvant chemotherapy (AC) were evaluated. Forty patients received AC (AC(+) group) and 73 patients did not (AC(-) group). Two-year relapse-free survival (RFS) rates of the AC(+) and AC(-) groups were 30.0% and 28.8%, respectively (p = 0.47). These patients were further divided into two subgroups, i.e., those with 3-6 positive lymph nodes (3-6 subgroup) and those with ≥ 7 positive lymph nodes (≥ 7 subgroup). Within the 3-6 subgroup (72 patients), 2-year RFS rates of the AC(+) and AC(-) groups were 38.5% and 33.9%, respectively (p = 0.31). Within the ≥ 7 subgroup (41 patients), 2-year RFS rates of the AC(+) and AC(-) groups were 25.9% and 7.1%, respectively (p = 0.04). AC may offer a significant additional benefit to the prognosis of esophageal cancer patients who have many positive lymph nodes even after NAC.

Effectiveness and toxicity of adjuvant chemotherapy in patients with non-small cell lung cancer.

ABSTRACTObjective:Adjuvant chemotherapy (AC) improves survival of patients with resected non-small cell lung cancer (NSCLC). However, the cisplatin-vinorelbine regimen has been associated with a significant risk of clinically relevant toxicity. We sought to evaluate the effectiveness, safety, and feasibility of AC for NSCLC patients in a real-world setting. Methods:This was a single-center, retrospective cohort study of patients with stage I-III NSCLC undergoing surgery with curative intent between 2009 and 2018. AC was administered at the discretion of physicians. The patients were divided into two groups: AC group and no AC (control) group. Study outcomes included overall survival (OS) and recurrence-free survival (RFS), as well as the safety profile and feasibility of the cisplatin-vinorelbine regimen in a real-world setting. Results:The study involved 231 patients, 80 of whom received AC. Of those, 55 patients received the cisplatin-vinorelbine regimen. Survival analyses stratified by tumor stage showed that patients with stage II NSCLC in the AC group had better RFS (p = 0.036) and OS (p = 0.017) than did those in the no AC group. Among patients with stage III NSCLC in the AC group, RFS was better (p < 0.001) and there was a trend toward improved OS (p = 0.060) in comparison with controls. Of those who received the cisplatin-vinorelbine regimen, 29% had grade 3-4 febrile neutropenia, and 9% died of toxicity. Conclusions:These results support the benefit of AC for NSCLC patients in a real-world setting. However, because the cisplatin-vinorelbine regimen was associated with alarming rates of toxicity, more effective and less toxic alternatives should be investigated.

The Effectiveness of Postoperative Chemotherapy on pT1bN0 and pT2N0 Gastric Cancer Patients with Risk Factors: An International Dual-Center Analysis.

PurposeThis study aimed to investigate the effectiveness of postoperative chemotherapy in pT1bN0 and pT2N0 gastric cancer patients with high risk factors.Materials and MethodsClinicopathological data of gastric cancer patients, who had undergone gastrectomy in high volume centers in Korea and China and were finally diagnosed with pT1bN0 and pT2N0 between 2006 and 2010, were analyzed retrospectively. Survival analyses stratified by risk factors and multivariable analyses were performed.ResultsA total of 1509 patients were enrolled, with 41 (2.7%) patients receiving adjuvant chemotherapy after gastrectomy and 1468 (97.3%) patients undergoing surgery alone. The adjuvant chemotherapy group showed higher percentages of tumor with maximal diameter >3 cm (51.2% vs. 25.8%), poor differentiation (68.3% vs. 49.8%), and less harvested lymph nodes (17.1% vs. 5.2%) compared to the surgery alone group. The overall survival rates were 95.1% in the adjuvant chemotherapy group and 93.3% in the surgery alone group, without significant difference. In multivariable analysis, age was found to be an independent prognostic factor. However, there were no difference in the overall survival between patients with risk factors and those without risk factors, even in terms of age. Meanwhile, patients with more than two risk factors who received chemotherapy showed better survival trend, especially for pT2N0 patients, compared to the surgery alone group, although no significant differences were observed.ConclusionIn pT1bN0 and pT2N0 patients, age was found to be an independent prognostic factor. However, adjuvant chemotherapy seemed to be unnecessary, while postoperative chemotherapy might offer survival benefits to pT2N0 patients with more than two risk factors.

Impact of Multimodality Treatment Sequence on Survival in Stage IIB Non-Small Cell Lung Cancer

The value of neoadjuvant treatment in combination with resection as multimodality therapy (MMT) for stage IIB non-small cell lung cancer remains controversial. This was a national cohort study of patients with clinical stage IIB non-small cell lung cancer (2006 to 2015) that used the National Cancer Database. Cohorts were defined on the basis of the MMT sequence and were categorized as follows: surgery plus adjuvant chemotherapy (AC), surgery plus adjuvant chemoradiation (ACRT), neoadjuvant therapy plus surgery (NA), surgery-alone, and definitive chemotherapy or chemoradiation (nonsurgical). The primary comparison was between the NA and AC cohorts. Propensity matching methods were used to match cohorts who had AC vs NA. Multivariable Cox regression was used to analyze the difference in risk of death between the NA and AC groups. There were 10,841 patients with stage IIB lung cancer: 2476 in the AC, 854 with ACRT, 1195 with NA, 2019 with surgery alone, and 4297 with nonsurgical treatment. Of the 6544 patients who underwent surgery, 37.8% had AC, 13.1% had ACRT, 18.3% had NA, and 30.9% had surgery alone. Relative to those patients treated with AC, nonsurgical treatment (hazard ratio [HR], 2.92; 95% confidence interval [CI], 2.69 to 3.17) or surgery-alone (HR, 1.26; 95% CI, 1.14 to 1.38) was associated with a significantly higher risk of death. After propensity matching, there was no difference in the risk of death between the NA and AC cohorts (HR, 1.07; 95% CI, 0.88 to 1.31). MMT, including surgical resection, is associated with improved OS, regardless of treatment sequence, with no difference in survival on the basis of an NA or AC approach. The potential benefits of NA over AC to ensure that patients complete MMT warrant further prospective investigation.

The Role of Adjuvant Chemotherapy in Non-Metastatic Goblet Cell Carcinoid of the Appendix: An 11-Year Experience from the National Cancer Database.

Goblet cell carcinoids (GCC) are an aggressive, albeit rare, subtype of appendiceal tumors that exhibit distinct histologic features and lack clear treatment guidelines. We aimed to ascertain the impact of adjuvant chemotherapy (AC) for GCC in a national cohort of patients. Patients who underwent a right hemicolectomy for stage I-III GCC of the appendix between 2006 and 2016 were selected from the National Cancer Database (NCDB). Stratification based on AC receipt was performed. Kaplan-Meier survival estimates and Cox proportional hazard regression were used to identify predictors of overall survival (OS). A total of 867 patients were identified, of whom 124 (14%) received AC. Patients in the AC group were significantly younger (54 vs. 57years; p = 0.006) and were predominantly of male sex (60 vs. 48%; p = 0.012). On histopathology, patients in the AC group had a higher proportion of poorly/undifferentiated grade (27 vs. 5%; p < 0.001), T4 disease (35 vs. 11%; p < 0.001), and lymph node-positive disease (45 vs. 7%; p < 0.001) than patients who did not receive AC. After excluding patients diagnosed in 2016 due to a lack of follow-up data (n = 162), a survival advantage for the AC group was detected only after stratification for lymph node-positive disease (p = 0.007). On Cox proportional hazard regression, AC demonstrated an independent association with improved OS (hazard ratio 0.24, 95% confidence interval 0.084-0.683; p = 0.007). The current analysis from the NCDB supports the role of AC for GCC of the appendix, chiefly for patients with lymph node metastatic disease.

Adjuvant chemotherapy as a risk factor for chronic postoperative pain after video-assisted thoracoscopic surgery: a 10-year single-centre retrospective study.

The association between adjuvant chemotherapy (AC) and chronic postoperative pain (CPP) after video-assisted thoracoscopic surgery (VATS) for lung cancer resection has not yet been reported. We, therefore, investigated the association between AC and the long-term incidence of CPP after VATS. We retrospectively reviewed 3015 consecutive patients who underwent VATS for lung cancer between 2007 and 2016. The patients were divided into 2 groups: those who received (AC group) and those who did not receive (non-AC group) AC within 3 months after VATS. Propensity score analysis was performed to adjust for baseline differences between the 2 groups. The cumulative incidence of CPP at the intervals of 3 months, over 36 months, was compared before and after matching. A Cox proportional hazards regression analysis was used to investigate the predictors of CPP after VATS. We included and assessed 2222 patients in this study. Of these, 320 patients (14.4%) received AC within 3 months post-VATS. The cumulative incidence of CPP during 36 months post-surgery was significantly higher in the AC group than in the non-AC group, before and after matching (log-rank test; P = 0.002 and 0.027, respectively). Cox proportional hazards regression analysis also showed that AC was a significant risk factor for CPP (hazard ratio 1.62, 95% confidence interval 1.16-2.28; P = 0.005). Our results indicate that AC is an important risk factor for CPP after VATS. Further understanding of the risk factors for CPP may facilitate its prediction and treatment.

N1c colon cancer and the use of adjuvant chemotherapy: a current audit of the National Cancer Database.

Colorectal cancer staging has evolved to define N1c as the presence of tumour deposits without concurrent positive lymph nodes. Work to date reports poor prognosis in N1c colon cancer, with Stage III categorization and adjuvant chemotherapy (AC) recommended. No study has yet evaluated the prevalence, treatment compliance or treatment-related outcomes on a national scale. We aimed to evaluate the prevalence of N1c colon cancer, use, outcomes and factors associated with AC in the USA. The National Cancer Database was reviewed for N1cM0 colon adenocarcinomas that underwent resection from 2010 to 2016. Cases were stratified into 'AC' or 'no AC' cohorts. The Kaplan-Meier method was used to estimate overall survival (OS) and compare the AC and no AC cohorts using the log-rank test. Multivariable logistic regression identified factors associated with AC. The main outcome measures were the prevalence and factors associated with AC use and its impact in N1c disease. Of the 5684 (1.59% of 357752) colon adenocarcinomas that were N1c, 55% (n=3071) received AC. AC significantly improved 1-, 3- and 5-year OS compared with no AC (96.2%, 80%, 67.4% and 72.9%, 48.5%, 33.8%, respectively; P<0.001). Compared with the no AC group, AC patients were younger, had less comorbidity, were of the male gender and received minimally invasive surgery at an academic treatment centre (all P<0.05). Socioeconomic and procedural factors significantly impacted the use of AC. In the USA, AC is underutilized in N1c colon cancer despite significantly improved OS. Socioeconomic and procedural factors associated with AC were identified, highlighting disparities in AC use and opportunities to improve oncological outcomes and survival.

Adjuvant Chemotherapy for Resected Ampulla of Vater Carcinoma: Retrospective Analysis of 646 Patients

PurposeThis study evaluated the efficacy of adjuvant chemotherapy (AC) in patients with resected ampulla of Vater (AoV) carcinoma.Materials and MethodsData from 646 patients who underwent surgical resection at Asan Medical Center between 2000 and 2017 were retrospectively reviewed.ResultsThe median age of the patients was 62 years, and 54.2% were male. Patients were classified into AC group (n=165, 25.5%) and no AC group (n=481, 74.5%). With a median follow-up duration of 88 months, in patients with stage I, II, III, median recurrence-free survival (RFS) was not reached, 44 months, and 15 months, respectively, and the median overall survival (OS) were not reached, 88 months and 35 months, respectively. Despite no statistical significance, RFS and OS were better in stage II patients with AC than in those without AC (median RFS, 151 months vs. 38 months; p=0.156 and median OS, 153 months vs. 74 months; p=0.299). In multivariate analysis for RFS and OS, TNM stage, R1 resection status, presence of lymphovascular invasion, and perineural invasion remained significant factors, whereas AC (hazard ratio [HR], 0.74; 95% confidence interval [CI], 0.54 to 1.00; p=0.052) was marginally related with RFS. After propensity score matching in only stage II/III patients, RFS and OS with AC were numerically longer than those without AC (HR, 0.80; 95% CI, 0.60 to 1.06; p=0.116 and HR, 0.77; 95% CI, 0.56 to 1.06; p=0.111).ConclusionAC with fluoropyrimidine did not improve survival of patients with resected AoV carcinoma. However, multivariate analysis with prognostic factors showed a marginally significant survival benefit with AC.

145P A nomogram for predicting the benefit of adjuvant chemotherapy after resection in patients with Borrmann type IV gastric cancer

This study sought to explore prognostic factors for patients with Borrmann type IV gastric cancer and to establish a predictive model for survival benefit of postoperative adjuvant chemotherapy in such patients. This study reviewed the clinical data of patients who underwent curative surgery at Fujian Medical University Union Hospital from 2006 to 2014 for Borrmann type IV gastric cancer using a prospective database. Cox regression analyses were performed to identify prognostic factors that formed the basis for a nomogram and risk groups. Establishment of risk groups to identify patients with Borrmann type IV gastric cancer who would benefit from adjuvant chemotherapy. 265 patients who underwent R0 resection were included in this study.Multivariate analysis showed that BMI, tumour differentiation, pT stage, pN stage, and ASA score were independent prognostic factors. Patients in the ACT-group had longer OS than patients in the SA-group, although the p-value for this difference was marginally above the threshold for statistical significance (23.8% vs. 10.9%, p=0.057). Stratified analysis showed that there was no significant difference in OS between the ACT-group and the SA-group for each AJCC stage (stage II: 40.6% vs. 29.8%, p=0.44; stage III: 21.4% vs. 9.7%, p=0.056).A nomogram was established based on these independent risk factors, and nomogram scores were used to divide all patients into a high-risk group (score>16), an intermediate-risk group (8<score≤16) and a low-risk group (score≤8).Further stratified analysis based on AJCC stage showed that the 3-year survival rate was higher in the adjuvant chemotherapy group than in the surgery alone group for low- and intermediate-risk patients in each AJCC stage, while high-risk patients in stage III did not significantly differ. The nomogram that we established may effectively be used to identify patients with Borrmann type IV gastric cancer who would benefit from postoperative adjuvant chemotherapy. Postoperative adjuvant chemotherapy can improve survival in low- and intermediate-risk patients.

Adjuvant Chemotherapy Improves Survival in pN-positive Clinical Stage IIIA Non-Small Cell Lung Cancer After Neoadjuvant Therapy and Resection

The utility of adjuvant chemotherapy (AC) after neoadjuvant therapy and curative intent surgery for clinical stage IIIA (cIIIA) non-small cell lung cancer (NSCLC) is not defined. We sought to evaluate the contribution of AC to overall survival (OS) in patients with cIIIA NSCLC who underwent neoadjuvant therapy followed by curative intent surgical resection. The National Cancer Database was queried from 2010 to 2016 for patients with cIIIA NSCLC who underwent curative intent surgical resection after neoadjuvant therapy. Patients were grouped by receipt of AC, and OS was calculated using the Kaplan-Meier method. The association between mortality and AC was evaluated using Cox regression. Ninety-day landmark and propensity score-matched analyses were performed to address bias associated with early postoperative morbidity and mortality. Of 3847 patients who met the inclusion criteria, 780 received AC (20.2%). In the unadjusted cohort there was no difference in 5-year OS between the AC and no AC groups (42.8% vs 43.9%, P= .105). Cox regression demonstrated a decreased risk of mortality in pN > 0 patients receiving AC (hazard ratio, 0.79; 95% confidence interval, 0.68-0.92; P < .003), whereas no difference was seen in node-negative patients (hazard ratio, 0.95; 95% confidence interval, 0.78-1.17; P= .64). In the propensity score-matched groups OS was significantly increased in pN > 0 patients who received AC (5-year OS: 42.4% vs 37%, P < .01), whereas no survival benefit was seen in those who were pN0. For patients with completely resected cIIIA NSCLC after neoadjuvant therapy, AC is associated with an increase in OS for patients with residual pathologic lymph node involvement.

Significance of mesothelin expression in preoperative endoscopic biopsy specimens for colorectal cancer prognosis.

Mesothelin (MSLN) is a cell surface glycoprotein that is normally expressed in the mesothelial cells but highly expressed in several malignant tumors, where the high expression is generally associated with poor prognosis. In this work, 512 patients with stage III colorectal cancer (CRC) were examined to ascertain the prognostic value of MSLN expression in preoperative endoscopic biopsy specimens. MSLN expression was evaluated by immunohistochemical staining. The tumor cells were MSLN-positive in 61 of the 512 patients (11.9%). MSLN expression was associated with a shorter disease-specific survival (DSS) period (5-year DSS = 68.7%, P = 0.0008). Besides, by multivariate analysis, MSLN expression was identified to be a marker of poor prognosis by multivariate analysis (P = 0.0033, hazard ratio (HR) = 2.31) as well as macroscopic type (P = 0.047, HR = 1.82) among the factors that can be evaluated preoperatively. MSLN-positive patients had a significantly poorer prognosis regardless of adjuvant chemotherapy administration (P = 0.0081 and P = 0.0018 for surgery alone and chemotherapy, respectively). MSLN-positive patients in the adjuvant chemotherapy group exhibited a significantly lower risk of recurrence when compared with those in the surgery alone group (P = 0.0090). In conclusion, high MSLN expression observed in preoperative endoscopic biopsy specimens of stage III CRC was an independent poor prognostic factor. Preoperative evaluation of MSLN by immunohistochemical staining might be applied to select individuals for intensive preoperative chemotherapy among the stage III CRC patients.

Outcome of Treatment After Locoregional Radiation, Neoadjuvant and Adjuvant Chemotherapy for Breast Cancer

The addition of systemic therapy to locoregional treatment for women with all stages of breast cancer improves survival. Reliable data are lacking about the outcomes of women with breast cancer in low-middle income countries who are treated with a combination of radiotherapy (RT), surgery, and systemic therapy. report the outcome of women with breast cancer treated with either neoadjuvant chemotherapy (NACT) or adjuvant chemotherapy at the National Centre for Radiotherapy and Nuclear Medicine in Accra, Ghana. The medical charts of all women with breast cancer managed at the National Centre for Radiotherapy and Nuclear Medicine from 2005 to 2014 were reviewed. Available patient specific demographic data, tumor stage, treatment sequence, and follow-up information were recorded. Logistic regression was used to estimate the presence of locoregional (LRR) and distant recurrence (DR) between two chemotherapy groups. Overall survival (OS) and disease-free survival (DFS) were used as time dependent outcomes and were analyzed using cox proportional hazard (CPH) model. All the models were adjusted with clinico-pathologic variables and estimates were reported along with their 95% confidence interval (CI). A total of 387 patients with a median follow up of 48 months were included in the study. The median age at diagnosis was 51 years. 49.6% of women had advanced pathologic stage ≥pT3. 58.9% (n = 228) received adjuvant chemotherapy whereas 41.1 % (n = 159) received NACT. The majority of women (94.1%, n = 365) received RT. 18.4% (n = 67) underwent breast conservation therapy followed by RT to a mean dose of 48.8 Gy in 10-30 fractions, and 81.6% (n = 298) had a mastectomy followed by RT to a mean dose of 47.92 Gy in 10-30 fractions. In an adjusted logistic model, no difference was observed in LRR between patients receiving NACT compared to those receiving adjuvant chemotherapy (OR = 1.05, 95% CI {0.44 - 2.47}, p = 0.9). However, NACT recipients had a higher likelihood of DR (OR = 1.97, 95% CI, {1.24 – 3.15}, p = 0.004). In a multivariate analysis, no differences were observed in survival between the two chemotherapy groups (HR = 1.43, 95% CI, {0.91 – 2.26}, p = 0.1). There was a trend towards lower DFS within the NACT group compared to the adjuvant chemotherapy group, with patients receiving NACT having a 52% likelihood of lower DFS (HR = 1.52, 95% CI, {0.96 – 2.39}, p = 0.06). While many women present with late stage disease in Ghana, outcomes after trimodal therapy are comparable to what is observed in developed countries. Advanced stage of disease is significantly associated with recurrence and survival, hence early detection in a resource limited setting is crucial to optimal outcomes. To our knowledge, this is the first and largest study to report on the outcomes of women with breast cancer who receive standard of care treatment in Ghana.

Is Radical Surgery Alone Enough in T1-3N1a Colon Cancer?

Background: Low lymphatic tumor burden is associated with a better prognosis. However, it is uncertain whether those patients diagnosed as cN0 found to be pN+ could be a favorable subgroup in stage III disease. Radical surgery alone might avoid overtreatment in those patients.Methods: Eligible patients diagnosed with colon cancer without metastasis were recruited from the Surveillance, Epidemiology, and End Results (SEER) database from 2004 to 2016 using SEER*Stat 8.3.5 software (Surveillance Research Program, National Cancer Institute) and divided into two groups: surgery group (n = 3,081) and surgery followed by adjuvant chemotherapy group (n = 4,591). Overall survival (OS) and cause-specific survival (CSS) differences were assessed by Kaplan–Meier analysis, and survival differences were estimated with log-rank tests. Univariate and multivariate Cox proportional hazard regressions were used to assess hazard ratios (HRs) and 95% confidence intervals (CIs) for colon cancer patients.Results: A total of 7,672 pT1-3N1a colon cancer patients were recruited from 208,751 colon cancer patients. The 5-year CSS rates of patients without and with adjuvant chemotherapy were 80.0 and 90.7%, respectively. The receipt of adjuvant chemotherapy after the radical resection of the primary tumor was independently associated with 57.3% decreased risk of colon cancer-specific mortality compared with surgery alone (HR = 0.427, 95% CI = 0.370–0.492, P < 0.001, using surgery alone as the reference).Conclusions: Adjuvant chemotherapy was significantly associated with improved prognosis and radical surgery alone did not provide enough treatment for colon cancer with very low lymphatic tumor burden.

Evaluating the Impact of ESPAC-1 on Shifting the Paradigm of Pancreatic Cancer Treatment

BackgroundIn 2004, the European Study Group for Pancreatic Cancer (ESPAC)-1 long-term data concluded that adjuvant chemotherapy provided a survival benefit for patients with pancreatic ductal adenocarcinoma (PDAC), whereas adjuvant chemoradiation was associated with worse overall survival. In this study, we investigated how long it took for US practice patterns to change following this trial. MethodsThe National Cancer Database was used to identify patients with stage I-III PDAC who underwent R0 or R1 resection followed by adjuvant chemotherapy or chemoradiation between 1998 and 2015. A multivariate analysis was performed to determine predictors of receiving adjuvant chemoradiation in the post-ESPAC-1 era. ResultsBetween 1998 and 2015, adjuvant chemotherapy use increased from 2.9% to 51.6%, whereas adjuvant chemoradiation decreased from 49.5% to 22.9%. In 2010, adjuvant chemotherapy utilization surpassed that of chemoradiation. For patients diagnosed in the post-ESPAC-1 era, adjuvant chemotherapy (n = 7733) and chemoradiation (n = 6969) groups were compared. Patients who underwent adjuvant chemoradiation were younger, had private insurance, underwent surgery at nonacademic centers, and had more pathologically advanced cancers (all P < 0.01). After 2010, R1 resection was the strongest independent predictor of adjuvant chemoradiation use by multivariate analysis (OR 2.05, CI 1.8-2.3, P < 0.01). ConclusionsAdjuvant chemotherapy use exceeded that of adjuvant chemoradiation 6 y after the final publication of ESPAC-1 in 2004, highlighting the challenges of disseminating and adopting clinical data. After 2010, R1 disease was the most significant predictor of receiving adjuvant chemoradiation. Prospective studies are underway to definitively address the role of adjuvant chemoradiation in PDAC.

377A Poster - Factors affecting locoregional recurrence rate of breast conserving surgery in patients with neoadjuvant chemotherapy

Background: Breast conserving surgery(BCS) is preferred over traditional mastectomy for better cosmetic and non-inferior oncological outcome. BCS is best indicated for early stage breast cancer with relatively small tumor size. Neo-adjuvant chemotherapy(NAC) helps downstaging locally advanced breast cancer and increase the possibility for BCS. However, recent meta-analysis from the Early Breast Cancer Trialists’ Collaborative Group (EBCTCG) showed a higher locoregional recurrence(LLR) rate in the NAC group than in the adjuvant chemotherapy group. Thus, the aim of this study was to retrospectively explore the factors affecting the LRR rate in breast cancer patients receiving BCS after NAC.

Adjuvant Chemotherapy in Two-Stage Tissue Expander/Implant Breast Reconstruction: Does it Affect Final Outcomes?

In immediate two-stage implant-based breast reconstruction, adjuvant chemotherapy, when indicated, is usually conducted between the stages, which might influence the outcomes of the second-stage operation. The purpose of this study was to evaluate the potential influence of adjuvant chemotherapy on the final outcomes of two-stage implant-based reconstructions. Patients who underwent immediate tissue expander/implant breast reconstruction between 2010 and 2016, with completion of both stages, were reviewed. Cases were categorized into two groups-adjuvant chemotherapy and no adjuvant chemotherapy. The rates of adverse outcomes were compared between the groups. A total of 602 cases in 568 patients were analyzed, with a mean follow-up period of 58.5months, including 236 patients receiving adjuvant chemotherapy and 366 patients not receiving adjuvant chemotherapy. The two groups had similar baseline characteristics, except for a significantly higher rate of adjuvant radiotherapy in the former group. The adjuvant chemotherapy group showed significantly higher rates of overall complications (odds ratio [OR] 2.127, 95% confidence interval [CI] 1.231-3.676), including infections (OR 4.239, 95% CI 1.059-16.970), severe capsular contractures (OR 2.107, 95% CI 1.067-4.159), and reconstruction failures (OR 12.754, 95% CI 1.587-102.481) compared with the control group, after adjusting for other variables, including adjuvant radiotherapy. In the analysis regarding the influence of chemotherapy regimens, the use of sequential anthracycline/cyclophosphamide and taxane, and concurrent 5-fluorouracil, doxorubicin and cyclophosphamide, were associated with increased risks for adverse outcomes compared with the no chemotherapy group, while the use of other regimens, including anthracycline/cyclophosphamide alone, was not. Adjuvant chemotherapy might influence the final outcomes of two-stage implant-based reconstruction.