Adjuvant Chemotherapy Group Research Articles

TS-1 add-on therapy in Japanese patients with triple-negative breast cancer after neoadjuvant or adjuvant chemotherapy: a feasibility study

SummaryPurpose We examined the feasibility, efficacy, and safety of TS-1 add-on therapy (TAT) in Japanese patients with triple-negative breast caner (TNBC). Methods TAT (TS-1, 80 mg/m2/day, BID, PO), consisting of the 21-day cycles of 14-day consecutive administration followed by 7-day drug holiday, was conducted for 365 days. The median follow-up was 75.2 months (range, 7.3–103.3 months). The primary endpoint was the feasibility of TAT. The secondary endpoints included relapse-free survival (RFS), overall survival (OS), and safety. Results 63 Japanese patients with TNBC (median age, 52.5 years; range, 23.7–68.6 years) were examined. Among them, 34 (54.0%) were postmenopausal, 54 (93.7%) had TNBC of common histological type, 51 (81.0%) had T1 to 3 tumors, 63 (100%) had undergone standardized surgery, and 44 (69.8%) and 19 (30.2%) had undergone neoadjuvant chemotherapy and adjuvant chemotherapy, respectively. The 365-day cumulative rate of TS-1 administration was 68.3% (95% confidence interval, 55.3–79.4), being comparable to 65.8% previously reported for gastric cancer. The 5-year RFS rates were 52.3% and 84.2% in the neoadjuvant and adjuvant chemotherapy groups, respectively, and the 5-year OS rates were 68.0% and 89.5%, respectively. The most common adverse events (AEs) were leucocyte count decreased (50.8%), total bilirubin decreased (44.4%), and pigmentation (42.9%). AEs were manageable clinically, and any grade 4 AEs did not develop. Conclusions The 365-day cumulative rate of TS-1 administration in TNBC patients was comparable to that in gastric cancer patients despite previous chemotherapy with anthracyclines and/or taxanes. TAT was feasible for TNBC patients after standard primary therapy.

Comparing the benefits of postoperative adjuvant chemotherapy vs. observation for stage IB non-small cell lung cancer: a meta-analysis.

The aim of this meta-analysis was to compare the benefits of postoperative adjuvant chemotherapy vs. observation for stage IB non-small cell lung cancer (NSCLC). A literature search was performed in PubMed, Embase, and Cochrane Library databases, and stage IB NSCLC patients were assigned to the postoperative adjuvant chemotherapy and observation groups. The 5-year overall survival (OS), 5-year disease-free survival (DFS), local recurrence, and distant metastasis were then assessed. In addition, statistical analysis was conducted using Review Manager 5.3 software. The meta-analysis involved nine articles and included 1,645 stage IB patients. There was no significance in the 5-year OS [relative risk (RR) =1.05; 95% confidence interval (CI): 0.98-1.13; P=0.14] and 5-year DFS (RR =1.29; 95% CI: 0.97-1.72; P=0.08) between the postoperative adjuvant chemotherapy and observation groups. However, there was a significant difference in local recurrence (RR =0.43; 95% CI: 0.23-0.80; P=0.007) and distant metastasis (RR =0.68; 95% CI: 0.48-0.97; P=0.03) between the two groups. Adjuvant chemotherapy might not be recommended for stage IB NSCLC.

Benefit of adjuvant chemoradiotherapy in patients with pathological stage III gastric cancer.

BackgroundFor patients with locally advanced gastric cancer (LAGC) after D2 gastrectomy, the survival benefits of receiving adjuvant chemoradiotherapy versus adjuvant chemotherapy are unclear. This study aimed to compare the 5- and 7-year overall survival (OS) in the two groups and to identify which patients can benefit more from adjuvant chemoradiotherapy.MethodsRetrospective data were collected from January 2009 to December 2014. The 5- and 7-year OS and disease-free survival (DFS) were compared between the two groups using the Chi-square test. The association of OS with prognostic factors was identified using the Cox’s proportional hazard model, which was then adjusted for survival coparison using propensity score-matching (PSM) analysis. The association of OS with each clinical/demographic factor was compared between the two groups using the Kaplan–Meier analysis.ResultsA total of 415 eligible patients were identified (135 adjuvant chemoradiotherapy, 280 adjuvant chemotherapy). Significant 5- and 7-year OS and DFS benefits were found in the adjuvant chemoradiotherapy group versus chemotherapy group. Multivariate analysis showed that age, TNM stage, lymph node (LN) ratio, tumor deposits, and total/subtotal gastrectomy were independent prognostic factors. When the PSM analysis was adjusting by these factors, 135 patients were matched with an improved survival benefit from adjuvant chemoradiotherapy. Patients in the adjuvant chemoradiotherapy group had a lower locoregional relapse. Subset analysis also identified significant OS benefits of adjuvant chemoradiotherapy in patients with LN ratio <50%, pIIIA, and pIIIB stage disease, while OS benefits were not observed in patients with tumor deposits, pN3b classification, or pIIIC stage disease.ConclusionAdjuvant chemoradiotherapy was shown to be superior in improving the OS in a certain population of patients compared with adjuvant chemotherapy. This finding may help to better guide the individualized treatments of patients with stage III LAGC after D2 gastrectomy.

Impact of histologic variants on the oncological outcomes of patients with upper urinary tract cancers treated with radical surgery: a multi-institutional retrospective study

No definitive evidence exists regarding the clinical significance of histologic variants (HV) in upper urinary tract cancer. We investigated the impact of HV on prognosis in patients with upper urinary tract cancer following radical surgery. We retrospectively analyzed 451 patients with upper urinary tract cancer who underwent radical nephroureterectomy at six affiliated hospitals from 1990 to 2015. Patients with distant metastatic disease prior to surgery and those who received neoadjuvant chemotherapy were excluded, leaving 441 eligible patients. Patients were classified into two groups: pure urothelial carcinoma (UC) and HV. The clinicopathological variables of each group were examined using Kaplan-Meier plots and proportional Cox hazard ratios (HR) to compare the oncological outcomes between the two groups. HV included 37 patients (8%). Compared with the pure UC patients, HV patients had significantly worse recurrence-free survival (RFS) and cancer-specific survival (CSS; RFS p = 0.0002, CSS p = 0.0001). Multivariate analysis for RFS revealed HV were independent predictors (HR 1.92; p = 0.026), but the association did not remain significant for CSS. There was no significant difference in CSS between the adjuvant chemotherapy (AC) group and the non-AC group for all HV patients, except in patients with ≥ pT3 tumor or positive lymph node status where the AC group had significantly favorable CSS. HV in upper urinary tract cancer are independent predictors for RFS, but not for CSS. AC improved CSS for HV patients with ≥ pT3 tumor or positive lymph node status.

Optimizing the Sequence of Chemotherapy for Upper Tract Urothelial Carcinoma with Clinically Positive Regional Lymph Nodes.

Upper tract urothelial carcinoma with clinically positive regional lymph nodes is an aggressive disease state with a high propensity for metastasis and death. The current literature is limited regarding national practice patterns and outcomes in this patient population. We identified 1,658 patients in the NCDB (National Cancer Database) who had cN+M0 upper tract urothelial carcinoma. Patients were stratified into treatment groups. We compared baseline patient and tumor characteristics between the groups, and completed survival analysis using a multivariate Cox regression model. There were 1,658 patients in the final study population. Preoperative chemotherapy was the least performed treatment. That group comprised 6.8% of the overall population and was associated with the highest median overall survival of 36 months compared to 21 months for adjuvant chemotherapy, 14 for chemotherapy only, 10 for surgery without perioperative chemotherapy and 5 for no treatment. On multivariate analysis preoperative chemotherapy was associated with improved median overall survival compared to that in the adjuvant chemotherapy group (HR 0.58, 95% CI 0.38-0.87). There was no statistically significant difference in survival between the chemotherapy only and the surgery only groups. Of patients in the preoperative chemotherapy group 34.6% achieved pN0 status compared to 10.3% of those who underwent surgery as initial therapy. Preoperative chemotherapy was the least performed treatment strategy in the management of cN+M0 upper tract urothelial carcinoma but it was associated with the highest median overall survival. There was no difference in survival between the chemotherapy only and the surgery only groups. Overall these results suggest that initial chemotherapy is appropriate in this population when feasible.

Does Neoadjuvant Chemotherapy Change the Role of Regional Lymphadenectomy in Pancreatic Cancer Survival?

The objective of this study was to evaluate the role of lymph node (LN) dissection and staging in outcomes of patients with pancreatic adenocarcinoma (PDAC) who underwent neoadjuvant chemotherapy (NAC). National Cancer Database was queried for patients with stages I to III PDAC diagnosed between 2004 and 2014. Overall survival (OS) was derived from Kaplan-Meier methods, and Cox-regression model was used to evaluate associations between the number of LN examined, number of positive nodes, and LN ratio with OS. A total 35,599 patients were included, 3395 (9%) underwent NAC, 19,865 (56%) received adjuvant chemotherapy (AC), and 12,299 (35%) underwent surgery alone. Cox-regression showed superior OS in NAC compared with AC and surgery alone (26 vs 23 vs 14 months, P < 0.001). Minimum number of LN examined affecting OS was 8 LNs in NAC (23.8 vs 26.6 months, P = 0.029), and 12 LNs in AC group (22 vs 23.1 months, P = 0.028). Lymph node ratio cutoff of greater than 0.2 was associated with decreased OS (19.4 vs 24.4 months, P < 0.001). Neoadjuvant chemotherapy is associated with improved survival in PDAC. Lymph node yield remains a significant prognostic factor after NAC, whereas the minimum number of harvested LNs associated with sufficient staging and survival is decreased.

Adjuvant chemotherapy versus observation after radical cystectomy in patients with node-positive bladder cancer

This retrospective study compared adjuvant chemotherapy (AC) versus observation after radical cystectomy (RC) in patients with node-positive bladder cancer (pN+). Outcomes were reviewed in patients with pTanyN1-3M0 bladder cancer who underwent RC with or without AC between 1995 and 2017. Baseline characteristics between the two groups were controlled with inverse probability of treatment weighting (IPTW)-adjusted analyses. Of 281 enrolled patients, the 3-year IPTW-adjusted rates of overall survival was higher in the AC group than the RC group (46.4% vs. 33.7%, p = 0.024). AC was an independent predictor of overall survival (hazard ratio = 0.48; P < 0.0001). When patients were subdivided by lymph node density (LND), the 3-year overall survival rates were similar between the AC and RC groups in patients with LND < 9%, but higher in the AC group in patients with LND 9–25% (53.4% vs. 23.7%) and LND ≥ 25% (27.4% vs. 16.1%). The numbers needed to treat to prevent one death at 3 years were three and nine in patients with LND 9–25% and ≥25%, respectively. In conclusion, AC after RC was associated with improved overall survival in patients with node-positive bladder cancer. Patients with an intermediate nodal burden may benefit most from AC.

Prognostic Impact of Increased Perioperative Platelet Count in Gastric Cancer Patients

BackgroundSolid tumors are a common cause of secondary (reactive) thrombocytosis, a paraneoplastic syndrome that is also a prognostic factor for various cancers. However, cutoff values for platelet count specific to gastric cancer and their prognostic roles are unknown. MethodsWe retrospectively analyzed records of 4643 patients with gastric cancer who underwent radical surgery from 2007 to 2010. The minimum P-value approach was used with the log-rank test to determine the optimal prognosis predicting threshold for preoperative platelet count. Change in perioperative platelet count over time was evaluated with a generalized estimating equation. Clinicopathologic features and prognostic significance were analyzed according to platelet count. ResultsThrombocytosis prevalence (platelet count ≥40 × 104/μL) was 1.6% (75 of 4643 patients). The platelet count cutoff value with the lowest P-value was ≥25.5 × 104/μL, and patients with higher platelet count had more advanced disease. Multivariate analysis showed that cutoff value was an independent prognostic factor of overall survival (hazard ratio 1.19, 95% confidence interval 1.03-1.37, P = 0.017). Patients who underwent adjuvant chemotherapy (n = 1300) and had a greater than 10% increase in platelet count at postoperative 1 y compared to before surgery had significantly poorer overall survival (hazard ratio 1.65, 95% confidence interval 1.11-2.45, P = 0.013). ConclusionsElevated preoperative platelet count (≥25.5 × 104/μL) and increased platelet count (≥10%) at postoperative 1 y in an adjuvant chemotherapy group were unfavorable prognostic factors. Platelet count could be a cost-effective biomarker for screening and monitoring patients with unfavorable survival outcomes.

Mucosal melanoma of the female genital tract: Operation modalities.

e21060 Background: Primary melanomas originating from the female genital tract are rare and aggressive. There are still no established guidelines for its primary surgery , so we analyzed the effect of the surgical approach on its relapse free survival (RFS) and overall survival (OS ) based on a phase 3 randomized trial (NCT03435302). Methods: Mucosal melanoma patients with female genital tract primary which were stageⅠ-Ⅲ and completely resected were enrolled as part of the multicenter, randomized, controlled, phase 3 trial for the comparison of adjuvant chemotherapy (TMZ plus DDP 6 cycles) vs. High-dose interferon group (HDI, 1 year).The RFS and OS was compared between local and extensive excision group. Results: Seventy eight female genital tract primary melanoma patients were enrolled from Feb 2014 to Jun 2016, Surgical approach was chosen by the surgeon, 39.2% (29/74) took local excision and 60.8% (45/74) extensive excision. The average age was 52.3 years. Of all these patients 46.2% were vulvar primary, 53.8% vaginal, and 85.3%stage I/II, 14.7% stage III. Primary ulceration was found in 68.1% lesions, 7 cases harbored with BRAF mutation. 57.7% patients randomized to adjuvant chemotherapy and 42.3% in HDI group. All these factors showed no difference in local excision and extensive excision group. At a median follow-up of 31.2 months (range: 5.3-60.0m), 64.4% got metastases and 23.1% showed local recurrence. RFS (8.0m vs. 11.4m, p = 0.523) and local recurrence rate (13.8% vs.31.1%, p = 0.105 ) did not show significant difference between local excision group and extensive excision group. OS in whole cohort was 28.9 months, it also did not show significant difference between two groups(local 25.5m vs. extensive 40.1m, p = 0.653). In univariate analysis there was also no relation between surgical approach and OS in this cohort. Conclusions: Based on this trial, for resectable female genital tract primary mucosal melanoma, there was no difference of local control rate, RFS and OS between local excision and extensive excision group. Local excision might be adequate for the primary leision. Still more prospective data are needed for this subtype of melanoma. Clinical trial information: NCT03435302.

Total cost of care for patients (pts) with stage II colon cancer (CC-II): A SEER-Medicare analysis.

6648 Background: Adjuvant chemotherapy (AC) for stage II colon cancer remains a controversial topic. We used Surveillance Epidemiology End Results (SEER) linkage with Medicare claims to explore the benefits of AC and cost of care in pts with CC-II diagnosed between 2004-2010. Methods: Colon cancer was identified using ICD-O-3 codes. TNM staging was used to classify pts as stage II. Cohort was restricted to pts who had surgery within 4months (mos) of the diagnosis and excluded pts who died within 3mos after the surgery as well as those who were enrolledon a health maintenance organization. We searched claims in the 4mos after surgery to identify pts who received AC using ICD-9 diagnosis and procedure codes, HCPCS, and revenue center codes. Kaplan-Meier method was used for survival analysis. Cost of care from payer’s perspective (Medicare) starting from surgery service to death or 3 years after surgery was captured from claims data. Results: A total of 16948 pts with CC-II diagnosed 2004-2010 were included in this analysis. Among those 14% received AC and 33% of them oxaliplatin. After adjusting for pts and tumor characteristics, probabilityof survival at 3years was 72.9% for pts who received AC and 74.2% for those who did not, HR=1.06 (95% CI, 0.96-1.17), with P-value: 0.229. The cost of care for the AC was significantly higher than the no-AC group (median $254,116 vs. $91,086). The biggest difference in between two groups was cost of outpatient and physician services. Costs for AC group was higher in years 1, 2, and 3 as seen in table. Conclusions: AC for CC-II is has a low value in elderly pts and should be avoided. [Table: see text]

&lt;p&gt;Adjuvant chemoradiotherapy versus adjuvant chemotherapy for patients with N3 gastric cancer after D2/R0 resection: a retrospective study based on propensity score analyses&lt;/p&gt;

Purpose: N3 gastric cancer (GC) is characterized by a heavy burden of lymph node metastasis and a high postoperative recurrence rate. The role of radiotherapy in this group of patients remains undetermined. The purpose of this study was to compare the effectiveness of adjuvant chemoradiotherapy (CRT) and adjuvant chemotherapy (ChT) for N3 GC after D2/R0 resection.Patients and methods: From January 2004 to December 2015, patients with N3 GC in the database of Fudan University Shanghai Cancer Center were retrospectively reviewed. The eligible patients were enrolled in an adjuvant CRT group and an adjuvant ChT group. Four different methods based on a propensity score model were used to balance the baseline characteristics. Then, survival analyses between the two groups were performed in addition to patterns of recurrence and subgroup analyses.Results: In total, 175 and 365 eligible patients were enrolled into the CRT and ChT groups, respectively. After balancing, the disease-free survival (DFS) of patients in the CRT group was significantly better than that of patients in the ChT group (p=0.021). Subgroup analyses showed that patients with N3a GC benefitted from adjuvant CRT.Conclusion: Compared with adjuvant ChT, adjuvant CRT can further improve the DFS of patients with N3 GC after D2/R0 resection. Patients with lymph node metastases should be further stratified when selecting patients for adjuvant CRT.

The Efficacy and Limitations of Postoperative Adjuvant Chemotherapy in Patients With Extrahepatic Cholangiocarcinoma.

The impact of adjuvant chemotherapy (AC) for extrahepatic cholangiocarcinoma (ECC) remains unclear. This study evaluated the efficacy and limitations of AC. Between 2006 and 2016, 106 patients with stage II-IV ECC who underwent curative resection with biliary tract reconstruction were retrospectively analyzed. Patients were divided into two groups: Those who received AC (n=57) and those who did not (n=49). Fewer grade 3-4 complications were observed in the AC group compared to the non-AC group (38.6 vs. 61.2%, p=0.03). In the non-AC group, complications were the most frequent reason for omitting AC (n=21, including 13 with biliary fistula). In the AC group, the therapy completion rate was 56.1% and the main reason for discontinuation was adverse events (n=12, including six with cholangitis). AC was not associated with survival benefits (median survival: 50.4 vs. 37.3 months, p=0.916). AC for ECC might be inadequate as a standard strategy due to the low implementation and completion rates because complications often hamper administration.

Concordance assessment of Watson for Oncology in breast cancer chemotherapy: first China experience.

BackgroundIBM Watson for Oncology (WFO) is an artificial intelligence cognitive computing system that provides confidence-ranked, evidence-based treatment recommendations for cancer. We examine the level of agreement for breast cancer chemotherapy between WFO recommended and clinical use in a large population of breast cancer cases.MethodsA total of 1,301 breast cancer patients were reviewed in The First Affiliated Hospital with Nanjing Medical University, China from June 2013 to December 2017. Patients’ data were entered manually into WFO by the trained senior oncology fellows. Chemotherapy recommendations were provided in 3 categories, “Recommended”, “For Consideration”, and “Not Recommended”. Concordance was achieved when oncologists’ treatment suggestions were in the “Recommended” or “For Consideration” categories.ResultsThe chemotherapy regimen concordance was 69.4% among all breast cancer cases, 65.0% among the cases in adjuvant chemotherapy (AC) group and 96.7% among the cases in neoadjuvant chemotherapy (NAC) group. The concordance varied greatly in subset analysis with respect to TNM stage and molecular subtype. AC recommendations were concordant in 92.3% of stage III breast cancer and 50.8% of stage I. However, the concordance varied by molecular subtype, which was higher for triple negative breast cancer (89.3%) than others. The chemotherapy regimen concordance declined significantly with increasing age, except for the age group 41–50 years.ConclusionsChemotherapy regimens provided by WFO did not exhibit a high degree of agreement with those suggested by oncologists in clinical practice in the hospital in China. The current effort is underway to enhance WFO’s capabilities as a cognitive decision support tool by incorporating regional guidelines, enabling oncologists and patients to benefit from WFO worldwide.

A Nomogram for Predicting Cancer-Specific Survival of TNM 8th Edition Stage I Non-small-cell Lung Cancer.

Models for predicting the survival outcomes of stage I non-small-cell lung cancer (NSCLC) defined by the newly released 8th edition TNM staging system are scarce. This study aimed to develop a nomogram for predicting the cancer-specific survival (CSS) of these patients and identifying individuals with a higher risk for CSS. A total of 30,475 NSCLC cases were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. We identified and integrated the risk factors to build a nomogram. The model was subjected to bootstrap internal validation with the SEER database, and external validation with a multicenter cohort of 1133 patients from China. The difference in the impact of adjuvant chemotherapy on model-defined high- and low-risk patients was examined using the National Cancer Database (NCDB). Eight independent prognostic factors were identified and integrated into the model. The calibration curves showed good agreement. The concordance index (C-index) of the nomogram was higher than that of the staging system (IA1, IA2, IA3, and IB) (internal validation set 0.63 vs. 0.56; external validation set 0.66 vs. 0.55; both p < 0.01). Specifically, 21.7% of stage IB patients (7.5% of all stage I) were categorized into the high-risk group (score > 30). There was a significant interaction effect between the adjuvant chemotherapy and risk groups in the NCDB cohort (p = 0.003). We established a practical nomogram to predict CSS for 8th edition stage I NSCLC. A prospective study is warranted to determine its role in identifying adjuvant chemotherapy candidates.

Neoadjuvant vs. adjuvant chemotherapy for cholangiocarcinoma: A propensity score matched analysis

BackgroundChemotherapy is frequently used in cholangiocarcinoma as an adjunct to surgical resection, but the appropriate sequence of chemotherapy with surgery is unclear. Patients and methodsUsing the National Cancer Database, we identified patients who underwent surgery and chemotherapy for stage I-III cholangiocarcinoma between 2006 and 2014. The propensity score reflecting the probability of receiving neoadjuvant chemotherapy was estimated by multivariate logistic regression method. Patients in the neoadjuvant and adjuvant chemotherapy study arms were then propensity-matched in 1:3 ratios using the nearest neighbor method. Overall Survival (OS) in the matched data set was estimated using the Kaplan-Meier method. Hazard ratios (HRs) were calculated using Cox proportional hazard regression model. ResultsOf the 1450 patients who met our inclusion criteria, 299 (20.6%) received neoadjuvant chemotherapy while 1151 (79.3%) received adjuvant chemotherapy. The median age at diagnosis was 63 years. 278 patients in the neoadjuvant group were matched to 700 patients in the adjuvant group. In the matched cohort, patients who received neoadjuvant chemotherapy had a superior OS compared to those who received adjuvant chemotherapy (Median OS: 40.3 vs. 32.8 months; HR: 0.78; 95% CI: 0.64–0.94, p = 0.01). The 1- and 5-year OS rates for the neoadjuvant chemotherapy group were 85.8% and 42.5% respectively compared to 84.6% and 31.7% for the adjuvant chemotherapy group. ConclusionIn this large national database study, neoadjuvant chemotherapy was associated with a longer OS in a select group of patients with cholangiocarcinoma compared to those who underwent upfront surgical resection followed by adjuvant chemotherapy.

Combination of lymphovascular invasion and the AJCC TNM staging system improves prediction of prognosis in N0 stage gastric cancer: results from a high-volume institution

BackgroundThis study sought to explore whether lymphovascular invasion can affect the prognosis of patients with stage N0 gastric cancer and to evaluate the survival benefit of adjuvant chemotherapy for such patients.MethodFrom January 2006 to December 2011, a total of 2102 gastric cancer patients undergoing radical gastric resection were enrolled in this study. Homogeneity, discriminatory ability, and monotonicity of gradients in the combination of lymphovascular invasion and the 8th edition of the AJCC staging system and the 8th edition of the AJCC staging system alone were compared using linear trend χ2, likelihood ratio χ2 statistics, and Akaike information criterion (AIC) calculations. The Kaplan-Meier method and the log-rank test were used to analyze between-group differences in survival rate.ResultThe median follow-up time of the whole group was 58 months, and the average age of the whole group was 63.9 years (range 21–89 years). The 3-year and 5-year overall survival rates in N0 patients with lymphovascular invasion were lower than those in N0 patients without lymphovascular invasion (3-year OS: 78.3% vs 92.5%, 5-year OS: 70.0% vs 88.3%, p < 0.001). A multivariate analysis showed that age (p < 0.001), lymphovascular invasion (p < 0.001), and pT (p < 0.001) were independent risk factors for the prognosis of N0 patients. Compared with the 8th edition of the AJCC staging system alone, the 8th AJCC staging system combined with lymphovascular invasion demonstrated a better linear trend χ2, likelihood ratio χ2 statistics, and AIC value (68.99 vs 58.58, 70.18 vs 58.36, 1473.38 vs 1485.04). In pT3N0M0 patients with lymphovascular invasion, the 3-year and 5-year overall survival rates of the adjuvant chemotherapy group were higher than those of the surgery alone group (3-year OS: 83.3% vs 68.2%, 5-year OS: 72.3% vs 50.0%, p = 0.048).ConclusionLymphovascular invasion is an independent prognostic factor in N0 patients. The 8th AJCC staging system combined with lymphovascular invasion can improve the accuracy of the AJCC staging system for N0 patients. Moreover, adjuvant chemotherapy improves the survival of pT3N0M0 patients with lymphovascular invasion.

Analysis of the National Cancer Data Base (NCDB) on impact and trend of neoadjuvant chemotherapy in upper urinary tract urothelial cancer.

408 Background: Five year cancer specific survival rate is between 12- 70% for pT2 and higher UUTUC tumors. Adjuvant platinum based therapies have proven to improve Overall survival (OS) in observational series. Compromised renal function after surgery, delayed recovery from surgery pose challenge for adjuvant chemotherapy (AC). Thus, neoadjuvant chemotherapy (NAC) is an appealing option. However, there is only limited evidence on the role of NAC in UUTUC. Methods: We conducted a retrospective study of UUTUC (stage I- III) who underwent complete or partial nephroureterectomy with peri-operative chemotherapy. We then compared OS outcome among NAC vs AC groups. OS was calculated using Kaplan Meier analysis. Multivariate analysis was performed with Cox proportional hazard regression model to adjust for different variables. Results: Out of 50539 UUTUC patients reported in NCDB (2004-2016), 20121 met our inclusion criteria. 360 patients received NAC, 2617 received AC and 17144 received only surgery. Patients who received NAC were more likely to be younger, treated at academic centers, have Medicare and private insurance, have clinical T3 and higher tumor, have lower Charlson-Deyo Score (CDCC) score and undergo complete nephroureterctomy. One, three and five year OS among NAC and AC is depicted in table 1. With 150 months (m) follow up, median OS was 73.89 m for NAC and 54.14 m for AC group. A log rank test with p value=0.3437 shows no significant difference in survival rates of the two groups. Though consistent upward trend is observed in the use of NAC from 2004 to 2015, significantly higher percentages of patients still undergo only surgery without perioperative chemotherapy. Conclusions: Numerically higher mOS in NAC group was not statistically significant different from AC group. Use of perioperative chemotherapy appears to be much lower in UUTUC. Limitations that exist with this registry based study include lack of randomization, differences in surgical and radiation techniques, duration of chemotherapy, and provider/patient selection bias. Overall survival among two groups. [Table: see text]

The role of adjuvant chemotherapy for pT2-4 upper urinary tract urothelial cancer: Exploratory analysis of large multi-institutional study (JCOG1110A).

374 Background: Recently, it was presented that adjuvant chemotherapy (AC) after radical nephroureterectomy (RNU) improved metastasis-free survival in pT2-4 upper urinary tract urothelial cancer (UTUC) with a median follow-up of 17.6 months (POUT study). However, the impact of AC on other outcomes remains unclear, especially for pT2 disease. Methods: The large case-series study, JCOG1110A, included 2,744 patients with non-metastatic UTUC who underwent RNU in 30 institutions in Japan between 1995 and 2009. In this analysis, patients with prior history or synchronous bladder cancer, patients who received neoadjuvant chemotherapy were excluded. Patients who received AC except for GC (gemcitabine, cisplatin) or MVAC (methotrexate, vinblastine, doxorubicin, cisplatin) were also excluded. We extracted pT2-4 patients as study subjects from remaining patients, and identified 950 patients. The impact of AC on overall survival (OS) and extravesical recurrence-free survival (RFS) were examined by the multivariable Cox regression model in all patient and pT2, pT3-4 subgroups. Results: Of 244 pT2 and 706 pT3-4 patients with a median follow-up of 41.1 months, AC were performed in 34 (13.9%) and 183 (25.9%). In AC (+) group, high frequency of pT3-4 disease, high grade tumor, pathological node metastasis, lymphovascular invasion, and younger age were seen compared to AC (-) group. The 5-year survival of the AC (+) and AC (-) were 66.0% and 67.4% for OS, 58.0% and 57.8% for RFS, respectively. Multivariable analysis showed the improved outcome in AC (+) group on both OS and RFS in all patients (OS: HR 0.60, 95% CI 0.41-0.89, RFS: HR 0.71, 95% CI 0.51-1.00). Although AC had a great impact on OS in pT3-4 patients (HR 0.56, 95% CI 0.36-0.87), there was no clear impact on either OS or RFS in pT2 patients (OS: HR 0.81, 95% CI 0.32-2.07, RFS: HR 0.69, 95% CI 0.29-1.62). Conclusions: AC after RNU had the significant impacts on OS and RFS in pT2-4 UTUC patients. This tendency was seen strongly in pT3-4 patients, but not in only pT2 patients. The randomized trial is necessary to determine the utility of AC in UTUC patients, especially in pT2 patients. Clinical trial information: NCT01993979.

Role of adjuvant chemotherapy in advanced stage upper urinary tract urothelial carcinoma after radical nephroureterectomy: A competing risk analysis.

367 Background: To determine whether adjuvant chemotherapy (ACH) influences cancer-specific mortality, bladder cancer-specific mortality, and other-cause mortality in patients with locally advanced upper tract urothelial carcinoma (UTUC) following radical nephroureterectomy (RNU) through the use of competing risk analysis. Methods: Among 785 patients with UTUC who underwent RNU from 1994 through 2015, we analyzed 338 individuals with locally advanced UTUC (pathologic T3–T4 and/or positive lymph nodes) without distant metastases. Patients were classified into two groups according to receipt of ACH. The study endpoints were UTUC-, bladder cancer- and other cause-specific survivals. The association of potential risk factors with outcome was tested with the Fine and Gray regression model. Results: Overall, 42.6% (n = 144) received ACH following RNU. During a median follow-up duration of 31.5 months, rates of UTUC-, bladder cancer-, and other cause-mortalities were 32.5% (n = 110), 5.0% (n = 17), and 4.1% (n = 14), respectively. Of note, there were no significant differences in overall survival between the observation and ACH groups according to the competing risks of death (UTUC, bladder cancer, and other causes of death). Multivariate analysis showed that only older age at surgery (≥ 65 years; hazard ratio [HR] = 1.71) and positive resection margin (HR = 7.25) remained as poor predictors of UTUC-specific and bladder cancer-specific survival, respectively. Additionally, no factors were identified as independent predictors of other causes of death. Conclusions: In summary, through competing risk analysis, we demonstrated that postoperative chemotherapy did not improve UTUC-specific and bladder-cancer specific survival, nor other cause-specific survival, in patients with locally advanced UTUC who underwent RNU. These results can offer practical information for clinicians regarding treatment decision making in these patients, who are at high risk of death due to competing causes.

Concordance assessment of Watson for Oncology in breast cancer chemotherapy: first China experience

Background: IBM Watson for Oncology (WFO) is an artificial intelligence cognitive computing system that provides confidence-ranked, evidence-based treatment recommendations for cancer. We examine the level of agreement for breast cancer chemotherapy between WFO recommended and clinical use in a large population of breast cancer cases. Methods: A total of 1,301 breast cancer patients were reviewed in The First Affiliated Hospital with Nanjing Medical University, China from June 2013 to December 2017. Patients’ data were entered manually into WFO by the trained senior oncology fellows. Chemotherapy recommendations were provided in 3 categories, “Recommended”, “For Consideration”, and “Not Recommended”. Concordance was achieved when oncologists’ treatment suggestions were in the “Recommended” or “For Consideration” categories. Results: The chemotherapy regimen concordance was 69.4% among all breast cancer cases, 65.0% among the cases in adjuvant chemotherapy (AC) group and 96.7% among the cases in neoadjuvant chemotherapy (NAC) group. The concordance varied greatly in subset analysis with respect to TNM stage and molecular subtype. AC recommendations were concordant in 92.3% of stage III breast cancer and 50.8% of stage I. However, the concordance varied by molecular subtype, which was higher for triple negative breast cancer (89.3%) than others. The chemotherapy regimen concordance declined significantly with increasing age, except for the age group 41–50 years. Conclusions: Chemotherapy regimens provided by WFO did not exhibit a high degree of agreement with those suggested by oncologists in clinical practice in the hospital in China. The current effort is underway to enhance WFO’s capabilities as a cognitive decision support tool by incorporating regional guidelines, enabling oncologists and patients to benefit from WFO worldwide.