Benefit Of Adjuvant Chemotherapy Research Articles

Abstract 353: Expression of astrocyte-elevated gene-1 is associated with prognostic value of adjuvant chemotherapy in resectable stage III colorectal cancer

Abstract Background: Administration of postoperative adjuvant chemotherapy has reduced the risk of tumor recurrence and improved survival for patients with resected colorectal cancer (CRC). Regarding the prognostic factors, including pathologic features and gene mutation have major relevance for stage III disease, it is not well known whether they might help select patients who would fare favorably when received adjuvant chemotherapy. OBJECTIVE: Expression of astrocyte-elevated gene-1 (AEG-1), thymidylate synthase (TS), excision repair cross-complementation group 1 (ERCC1), epidermal growth factor receptor (EGFR), vascular endothelial growth factor (VEGF) were needed to investigate the role involved in adjuvant combination therapy for patients with resectable stage III colon cancer. Methods: AEG-1, TS, ERCC1, EGFR and VEGF were investigated by CRC cell lines and intra-tumor immunohistochemistry stain. Furthermore, this study collected 29 patients with stage III colorectal cancer who underwent surgical resection from 2011 to 2016 and received postoperative adjuvant chemotherapy. The culmination of clinical data registration included surgical procedures, tumor size, number of lymph node metastases, and types of chemotherapy drugs. Result: A significant positive correlation between AEG-1, TS, ERCC1, EGFR, and VEGF gene expression levels were revealed in CRC cell lines. Cell lines with lower AEG-1 and TS expression had higher sensitivity to 5-FU treatment. In clinical studies, we found that higher AEG-1 expression was noted in T4 and also caused CRC recurrence or metastasis. Patients with T4 and stage IIIC CRC had a significantly shorter DFS (T4 v.s. T1-3, DFS, months, median: 4.1 ± 1.2 v.s. non-reach [NR], p < 0.001; IIIC v.s. IIIA or IIIB, DFS, months, median: 10.6 ± 5.3 v.s. NR, p = 0.037; respectively). Patients with higher AEG-1 and TS expression had a shorter DFS (AEG-1, high v.s. low, months, median: 12.8 ± 2.4 v.s. NR, p = 0.003; TS, high v.s. low, months, median: 13.8 ± 2.3 v.s. NR, p = 0.012; respectively). In multivariate Cox Regression analysis, advanced tumor invasion (T4) and high AEG-1 expression could be an independent prognostic factor to cause poor survival in resectable stage III CRC patients treated with adjuvant chemotherapy. Conclusion: Expressions of AEG-1 and tumor grade as a candidate prognostic factor of recurrence in stage III colorectal cancer patients receiving adjuvant fluoropyrimidine-based chemotherapy. A prospective cohort study should be guaranteed to validate these factors to be predictive markers of adjuvant chemotherapy benefit for stage III CRC. Citation Format: Chung-Yu Chen, Peng-Sheng Lai, Ying-Yin Chen, Long-Wei Lin. Expression of astrocyte-elevated gene-1 is associated with prognostic value of adjuvant chemotherapy in resectable stage III colorectal cancer [abstract]. In: Proceedings of the Annual Meeting of the American Association for Cancer Research 2020; 2020 Apr 27-28 and Jun 22-24. Philadelphia (PA): AACR; Cancer Res 2020;80(16 Suppl):Abstract nr 353.

Benefit of adjuvant chemotherapy in high-risk colon cancer: A 17-year population-based analysis of 6131 patients with Union for International Cancer Control stage II T4N0M0 colon cancer

BackgroundThe benefit of adjuvant chemotherapy in Union for International Cancer Control (UICC) stage III colon cancer has been demonstrated in numerous studies. While adjuvant chemotherapy is generally not recommended in stage II patients, its role in high-risk UICC stage II disease (e.g. T4 tumours) remains controversial. MethodsThe present population-based multicenter cohort study investigated the influence of adjuvant chemotherapy on survival and recurrence rates in high-risk UICC stage II T4N0M0 tumours. Based on an anonymised nationwide ADT data set from 31 clinical cancer registries, we identified a total of 6651 patients with a T4 tumour of the colon, of whom 6131 were eligible for survival analysis. A matched-pair analysis based on propensity scores (PSM) was performed with a subset of 3986 patients. ResultsMultivariable analyses demonstrated a significant benefit of adjuvant chemotherapy for overall survival (OS) (hazard ratio [HR]: 0.711, 95% confidence interval [CI]: 0.643–0.785, p < 0.001), cumulative recurrence rate (HR: 0.780, 95% CI: 0.681–0.893, p < 0.001), and recurrence-free survival (HR: 0.715, 95% CI: 0.652–0.785, p < 0.001) further confirmed by the matched-pair cohort. ConclusionThis large and representative study demonstrated a significant advantage of adjuvant chemotherapy for patients with T4 UICC stage II colon cancer in terms of OS, recurrence rate, and relapse-free survival. Based on these results, adjuvant chemotherapy should be recommended for these patients.

An Immune Cell Signature is Associated with Disease-Free Survival and Adjuvant Chemosensitivity of Patients with Resectable Gastric Cancer

Background: Increasing evidence has demonstrated current TNM stage alone cannot predict prognosis and adjuvant chemotherapy benefits accurately for stage II and III gastric cancer (GC) patients after surgery. This study aimed to establish an immune signature, based on the composition of infiltrating immune cells, to improve the prediction of survival and adjuvant chemotherapy benefits of GC patients after surgery. Methods: Twenty-eight types of immune cell fraction were evaluated based on the expression profiles of GC patients from the Gene Expression Omnibus (GEO) database using single-sample gene set enrichment analysis (ssGSEA). The immunoscore was constructed using a least absolute shrinkage and selection operator (LASSO) Cox regression model. Findings: Using the LASSO model, an immunoscore (IS) classifier was established consisting of 8 immune cells. Significant difference was found between high-IS and low-IS groups in the training cohort in DFS (P<0.0001) and OS (P<0.0001). Multivariate analysis showed that the IS classifier was an independent prognostic indicator. Moreover, a combination of IS and TNM stage had better prognostic value than TNM stage alone. Further analysis demonstrated that low-IS patients had better response to adjuvant chemotherapy. Finally, we established two nomograms to screen the patients with stage II and III benefiting from adjuvant chemotherapy after surgery. Interpretation: The IS classifier, companied with TNM stage, could predict DFS and OS of GC patients effectively and precisely. The IS model represented a promising tool that could be used to identify the patients with stage II and III GC who might benefit from adjuvant chemotherapy. Funding Statement: This work was supported by the National Key Research and Development Program of China (2017YFC1308900), Technological Special Project of Liaoning Province of China (2019020176-JH1/103), Science and Technology Plan Project of Liaoning Province (NO.2013225585), The Key Research and Development Program of Liaoning Province (2018225060), The General Projects of Liaoning Province Colleges and Universities (LFWK201706), Science and Technology Plan Project of Shenyang city(19-112-4-099). Declaration of Interests: The authors declare no conflict of interests.

Molecular Classification of the PORTEC-3 Trial for High-Risk Endometrial Cancer: Impact on Prognosis and Benefit From Adjuvant Therapy

PURPOSEThe randomized Adjuvant Chemoradiotherapy Versus Radiotherapy Alone in Women With High-Risk Endometrial Cancer (PORTEC-3) trial investigated the benefit of combined adjuvant chemotherapy and radiotherapy (CTRT) versus radiotherapy alone (RT) for women with high-risk endometrial cancer (EC). Because The Cancer Genome Atlas defined an EC molecular classification with strong prognostic value, we investigated prognosis and impact of chemotherapy for each molecular subgroup using tissue samples from PORTEC-3 trial participants.METHODSParaffin-embedded tissues of 423 consenting patients were collected. Immunohistochemistry for p53 and mismatch repair (MMR) proteins, and DNA sequencing for POLE exonuclease domain were done to classify tumors as p53 abnormal (p53abn), POLE-ultramutated (POLEmut), MMR-deficient (MMRd), or no specific molecular profile (NSMP). The primary end point was recurrence-free survival (RFS). Kaplan-Meier method, log-rank test, and Cox model were used for analysis.RESULTSMolecular analysis was successful in 410 high-risk EC (97%), identifying the 4 subgroups: p53abn EC (n = 93; 23%), POLEmut (n = 51; 12%), MMRd (n = 137; 33%), and NSMP (n = 129; 32%). Five-year RFS was 48% for patients with p53abn EC, 98% for POLEmut EC, 72% for MMRd EC, and 74% for NSMP EC (P < .001). The 5-year RFS with CTRT versus RT for p53abn EC was 59% versus 36% (P = .019); 100% versus 97% for patients with POLEmut EC (P = .637); 68% versus 76% (P = .428) for MMRd EC; and 80% versus 68% (P = .243) for NSMP EC.CONCLUSIONMolecular classification has strong prognostic value in high-risk EC, with significantly improved RFS with adjuvant CTRT for p53abn tumors, regardless of histologic type. Patients with POLEmut EC had an excellent RFS in both trial arms. EC molecular classification should be incorporated in the risk stratification of these patients as well as in future trials to target specific subgroups of patients.

Radiomics nomogram for prediction disease-free survival and adjuvant chemotherapy benefits in patients with resected stage I lung adenocarcinoma.

BackgroundRobust imaging biomarkers are needed for risk stratification in stage I lung adenocarcinoma patients in order to select optimal treatment regimen. We aimed to construct and validate a radiomics nomogram for predicting the disease-free survival (DFS) of patients with resected stage I lung adenocarcinoma, and further identifying candidates benefit from adjuvant chemotherapy (ACT).MethodsUsing radiomics approach, we analyzed 554 patients’ computed tomography (CT) images from three multicenter cohorts. Prognostic radiomics features were extracted from computed tomography (CT) images and selected using least absolute shrinkage and selection operator (LASSO) Cox regression model to build a radiomics signature for DFS stratification. The biological basis of radiomics was explored in the Radiogenomics dataset (n=79) by gene set enrichment analysis (GSEA). Then a nomogram that integrated the signature with these significant clinicopathologic factors in the multivariate analysis were constructed in the training cohort (n=238), and its prognostic accuracy was evaluated in the validation cohort (n=237). Finally, the predictive value of nomogram for ACT benefits was assessed.ResultsThe radiomics signature with higher score was significantly associated with worse DFS in both the training and validation cohorts (P<0.001). The GSEA presented that the signature was highly correlated to characteristic metabolic process and immune system during cancer progression. Multivariable analysis revealed that age (P=0.031), pathologic TNM stage (P=0.043), histologic subtype (P=0.010) and the signature (P<0.001) were independently associated with patients’ DFS. The integrated radiomics nomogram showed good discrimination performance, as well as good calibration and clinical utility, for DFS prediction in the validation cohort. We further found that the patients with high points (point ≥8.788) defined by the radiomics nomogram obtained a significant favorable response to ACT (P=0.04) while patients with low points (point <8.788) showed no survival difference (P=0.7).ConclusionsThe radiomics nomogram could be used for prognostic prediction and ACT benefits identification for patient with resected stage I lung adenocarcinoma.

Recent trends in use of adjuvant chemotherapy in elderly stage II-III non-small cell lung cancer.

BackgroundAlthough randomized trials demonstrated survival benefit of adjuvant chemotherapy, previous reports have suggested that its use in elderly populations for early stage non-small cell lung cancer (NSCLC) was infrequent. The current status of adjuvant chemotherapy in this population is unknown.MethodsUsing the Surveillance, Epidemiology, and End Results (SEER) database, we examined the incidence of chemotherapy in resected stage II–III NSCLC between 2004 and 2015. Staging was determined according to the American Joint Committee on Cancer (AJCC) 6th version. Cases were grouped by age (20–69, 70–79, and 80+). Trends in use of chemotherapy by age group were assessed by univariate and multivariate analyses.ResultsA total of 35,009 cases were selected as surgically resected stage II–III NSCLC. Use of chemotherapy was 66.9%, 48.2%, 25.0% in age 20–69, 70–79, 80+, respectively. Multivariate analysis demonstrated that younger age [20–69] and recent year [2010–2015] of diagnosis were associated with increased use of chemotherapy. Chemotherapy use increased from 2004 to 2015 by 11.0%, 18.3%, and 11.3% in age 20–69, 70–79, 80+, respectively. In the age 70–79 group, increased use of chemotherapy was greater in stage II (24.3%) than stage III (14.1%). Five-year overall survival in age 70–79 group mildly increased by 7.6% from 2004 to 2011.ConclusionsThis study suggests that use of adjuvant chemotherapy in the elderly population increased primarily in age 70–79. Few patients in the 80+ age group received adjuvant chemotherapy even in recent years.

Gene dysregulation analysis builds a mechanistic signature for prognosis and therapeutic benefit in colorectal cancer.

The implementation of cancer precision medicine requires biomarkers or signatures for predicting prognosis and therapeutic benefits. Most of current efforts in this field are paying much more attention to predictive accuracy than to molecular mechanistic interpretability. Mechanism-driven strategy has recently emerged, aiming to build signatures with both predictive power and explanatory power. Driven by this strategy, we developed a robust gene dysregulation analysis framework with machine learning algorithms, which is capable of exploring gene dysregulations underlying carcinogenesis from high-dimensional data with cooperativity and synergy between regulators and several other transcriptional regulation rules taken into consideration. We then applied the framework to a colorectal cancer (CRC) cohort from The Cancer Genome Atlas. The identified CRC-related dysregulations significantly covered known carcinogenic processes and exhibited good prognostic effect. By choosing dysregulations with greedy strategy, we built a four-dysregulation (4-DysReg) signature, which has the capability of predicting prognosis and adjuvant chemotherapy benefit. 4-DysReg has the potential to explain carcinogenesis in terms of dysfunctional transcriptional regulation. These results demonstrate that our gene dysregulation analysis framework could be used to develop predictive signature with mechanistic interpretability for cancer precision medicine, and furthermore, elucidate the mechanisms of carcinogenesis.

Differential Benefit of Adjuvant Docetaxel-Based Chemotherapy in Patients With Early Breast Cancer According to Baseline Body Mass Index.

Lipophilic drugs, such as taxanes, have a high affinity for adipose tissue and a resulting higher volume of distribution. Here, we reanalyzed clinical trial data to investigate whether the efficacy of docetaxel-based chemotherapy differs from non-docetaxel-based chemotherapy in patients with breast cancer according to their baseline body mass index (BMI). We retrospectively analyzed data from all of the patients in the adjuvant BIG 2-98 trial (ClinicalTrials.gov identifier: NCT00174655; N = 2,887) comparing non-docetaxel- to docetaxel-containing chemotherapy. BMI (kg/m2) was categorized as follows: 18.5 to < 25, lean; 25 to < 30, overweight; and ≥ 30, obese. Disease-free survival (DFS) was the primary endpoint, and overall survival (OS) was the secondary endpoint. A second-order interaction was assessed among treatment, BMI, and estrogen receptor (ER) status. There was no difference in DFS or OS according to BMI in the non-docetaxel group, while reduced DFS and OS were observed with increasing BMI category in the docetaxel group. Adjusted hazard ratios for DFS and OS were, respectively, 1.12 (95% CI, 0.98 to 1.50; P = .21) and 1.27 (95% CI, 1.01 to 1.60; P = .04) for overweight versus lean groups and were 1.32 (95% CI, 1.08 to 1.62; P = .007) and 1.63 (95% CI, 1.27 to 2.09; P < .001), respectively, for obese versus lean groups. Similar results were obtained when considering ER-negative and ER-positive tumors separately and when considering only patients who received a relative dose intensity ≥ 85% for docetaxel. A joint modifying role of BMI and ER status on treatment effect was evident for DFS (adjusted P = .06) and OS (adjusted P = .04). This retrospective analysis of a large adjuvant trial highlights a differential response to docetaxel according to BMI, which calls for a body composition-based re-evaluation of the risk-benefit ratio of the use of taxanes in breast cancer. These results now must be confirmed in additional series.

P-151 The impact of adjuvant chemotherapy regimens in stage II colon cancer (CC) patients

The benefit of adjuvant chemotherapy (AdjCT) in all stage II patients (pts) with colon cancer is not clear. Characterization of high-risk subgroups may shed light on this matter. The aim of this study was to determine patterns of AdjCT prescription and its impact on disease-free survival (DFS) in stage II CC.

165 - A new promising risk stratifying tool based on combination of lymphovascular invasion and systemic immune-inflammation index to predict the survival and to help evaluate the potential benefit of adjuvant chemotherapy for upper tract urothelial carcinoma

165 - A new promising risk stratifying tool based on combination of lymphovascular invasion and systemic immune-inflammation index to predict the survival and to help evaluate the potential benefit of adjuvant chemotherapy for upper tract urothelial carcinoma

Oncotype DX Breast Recurrence Score®: A Review of its Use in Early-Stage Breast Cancer.

Oncotype DX Breast Recurrence Score® is a 21-gene prognostic and predictive assay indicated for use in patients with hormone receptor-positive, human epidermal growth factor receptor 2-negative, lymph node (LN)-negative or up to three LN-positive, early-stage breast cancer. The assay is used worldwide and is conducted at a CLIA-certified central laboratory in the USA. The 21-gene assay generates a Recurrence Score for each tumour sample, based on expression levels of 16 breast cancer-related genes, normalized to five reference genes. The Recurrence Score is a continuous variable that provides an individualized estimate of 9-year distant recurrence risk and the likelihood of adjuvant chemotherapy benefit. The 21-gene Recurrence Score assay is extensively validated in clinical studies, which are well supported by real-world registry studies. The assay informs treatment decisions and reduces adjuvant chemotherapy use in routine clinical practices, and is estimated to be cost-effective. The 21-gene Recurrence Score assay is included in all major international treatment guidelines. Currently, it is the only multigene assay validated for prediction of chemotherapy benefit, as well as for prognosis.

Clinical Outcomes and Prognostic Factors in Gastric Carcinoma Patients with Curative Surgery Followed by Adjuvant Treatment: Real-World Scenario.

A wide range of adjuvant treatment regimens exist in gastric carcinoma patients which include chemotherapy, radiotherapy, and/or both either sequential or concurrent. The study aimed to assess the benefit of adjuvant sequential chemotherapy followed by radiotherapy for operable gastric cancers and evaluatetheprognostic factors associated with clinical outcomes. Patients of stage IB-III gastric carcinoma who underwent radical surgery followed by adjuvant treatment from January 2013 to December 2016 were analyzed retrospectively. Survival was computed using Kaplan-Meier method and prognostic factors were analyzed in multivariate analysis using Cox progression hazard model. A P value < 0.05 was taken as statistically significant. A total of 108 patients were identified with a median follow-up of 31.7months (range: 6-96). Seventy-two percent of the patients received adjuvant sequential chemoradiation (N = 77) and 28% of patients received chemotherapy alone. The median survival was 26months (95% CI: 23.09-28.90). Overall survival (OS) rates for 1, 2, 3, 4, and 5years were 88.9%, 57.4%, 40.7%, 28.8%, and 20.4%, respectively. Five-year OS for stage-IB, II, and III was 75%, 45%, and 8.3%, respectively (p = 0.023). Surgical margin positivity (9.5% vs. 26.9%, p = 0.042), signet-ring cell histology (6.5% vs. 25.8%, p = 0.00), and adjuvant sequential chemoradiation (p = 0.002) showed a significant impact on survival outcomes and proved as independent prognostic factors. The present study demonstrated that survival in gastric carcinoma is influenced by the stage of disease and surgical margins. In locally advanced patients, radical surgery followed by sequential chemoradiation based on a doublet/triplet regimen was an independent prognostic factor for survival. Majority of patients in our set-up presented in locally advanced stage, curative resection followed by adjuvant sequential chemoradiation was an independent prognostic factor for survival.

Adjuvant chemotherapy for breast cancer after preoperative chemotherapy: A propensity score matched analysis.

Although identified to be at a higher risk of relapse, no consensus exists on the treatment of breast cancer (BC) patients with no pathological complete response after neoadjuvant chemotherapy (NAC). The benefit of adjuvant chemotherapy (ADJ) in this context has scarcely been studied. We evaluated the benefit of administrating adjuvant chemotherapy in a real life cohort of BC patients with invasive residual disease after NAC. 1199 female BC patients with T1-3NxM0 invasive tumors receiving NAC at Institut Curie from 2002 to 2012 were included in the analysis. 1061 had been treated by NAC only, whereas 138 had received additional adjuvant chemotherapy after NAC (FUN protocol: 5-FU-Vinorelbine). We compared disease-free survival (DFS) and overall survival (OS) rates between patients having received NAC only and patients having received NAC+ADJ. To ensure comparability of our populations, we used a propensity score (which defines the probability of treatment assignment conditional on observed baseline covariates) and matched each patient having received NAC+ADJ (n = 138) with a patient having received NAC only that had a similar propensity score value. Before propensity score matching, DFS and OS rates were significantly lower in the NAC+ADJ group compared to NAC only, after 3 years, 5 years and 10 years follow-up (p<0.01). After one-to-one PS matching, the two groups were comparable (n = 276 patients; 138 patients in each group). No significant difference was found regarding DFS (p = 0.87) or OS (p = 0.59) rates, neither in global population, nor by pathological subtype. Although our study did not show a benefit of administrating ADJ with FUN protocol (5-Florouracil- Vinorelbine) to BC patients with residual disease after NAC, further studies are warranted to determine the impact of other adjuvant regimens. Thereby, patients with little chance of responding to particular regimens could avoid the toxicity of futile therapy, and be study participants in evaluations of novel treatment strategies.

Stromal LAG-3+cells infiltration defines poor prognosis subtype muscle-invasive bladder cancer with immunoevasive contexture

BackgroundLymphocyte activation gene 3 (LAG-3) is a promising immune checkpoint therapeutic target being evaluated in clinical trials. We assessed the LAG-3+ cells distribution, its association with clinical outcomes and immune contexture and its role in the landscape of muscle-invasive bladder cancer (MIBC) treatment.Methods141 patients with MIBC from Zhongshan Hospital were included for survival and adjuvant chemotherapy (ACT) benefit analyses. 32 fresh resected samples of MIBC were collected to detect CD8+ T cells functional state. The molecular classification analyses were based on 391 patients with MIBC from The Cancer Genome Atlas. Immunohistochemistry and flow cytometry were performed to characterize various immune cells infiltration.ResultsIn Kaplan-Meier analyses and Cox regression models, stromal LAG-3+ cells enrichment was consistently associated with inferior overall survival and disease-free survival, and indicated suboptimal responsiveness to ACT. Patents with high stromal LAG-3+ cells possessed increased protumor cells, immunosuppressive cytokines and immune checkpoint expression. The phenotypic analyses of CD8+ T cells correlated its dysfunctional state with LAG-3+ cells. Besides, LAG-3 mRNA level was linked to luminal and basal subtypes of MIBC. LAG-3-high tumors exhibited limited FGFR3 mutation and signaling signature, and displayed activated immunotherapeutic and EGFR-associated pathway.ConclusionsStromal LAG-3+ cells abundance indicated an immunoevasive contexture with dysfunctional CD8+ T cells, and represented an independent predictor for adverse survival outcome and ACT resistance in MIBC. LAG-3 expression could potentially be a novel biomarker for FGFR3-targeted and EGFR-targeted therapies and immunotherapy. The crucial role of LAG-3+ cells in the therapeutic landscape of MIBC needs further validation retrospectively and prospectively.

13. ASSESSING THE ONCOTYPE DX BREAST RECURRENCE SCORE ASSAY ON CORE BIOPSY TO PREDICT RESPONSE TO NEOADJUVANT TREATMENT IN PATIENTS WITH BREAST CANCER - A SYSTEMATIC REVIEW AND META-ANALYSIS

Introduction: The Oncotype DX breast recurrence score (RS) has been validated to predict the benefits of adjuvant chemotherapy in patients with oestrogen receptor (ER)-positive, HER2-negative breast cancer. The use of Oncotype DX for predicting chemosensitivity in the neoadjuvant setting is not well established. This systematic review aimed to determine if RS performed on core needle biopsy at diagnosis predicted complete pathological response (PCR) to neoadjuvant chemotherapy (NACT) in patients with invasive breast cancer.

Adjuvant chemotherapy after radiotherapy or concurrent chemoradiotherapy for pelvic lymph node-positive patients with locally advanced cervical cancer: a propensity score matching analysis

ObjectiveThe benefit of adjuvant chemotherapy after definitive chemoradiotherapy in patients with pelvic lymph node-positive cervical cancer has been poorly studied. This study aimed to test the hypothesis that the addition...

Role of adjuvant chemotherapy in patients with pathological stage I NSCLC with high-risk features.

9022 Background: Lobectomy is the current standard of care for patients with stage I non-small cell lung cancer (NSCLC). There is a lack of prospective data on the benefit of adjuvant chemotherapy (CT) in patients with negative margins but with high-risk features: lympho-vascular invasion (LVI) or visceral pleural invasion (VPI). We aimed to investigate the benefit of adjuvant CT in patients with pathological stage I NSCLC with high-risk features. Methods: The 2016 National Cancer Database was queried to identify patients with pathological stage I NSCLC (8th edition AJCC staging) diagnosed from 2010-2015 who received lobectomy/pneumonectomy with clear surgical margins. Patients were stratified into high risk (tumor size ≥2 cm with LVI and/or VPI) or low risk group. Multivariate Cox proportional hazards regression and propensity score matched Kaplan-Meier survival analysis were used to compare overall survival between those who received adjuvant CT and those who did not. Results: 34,556 patients were identified with 1114 (3.2%) receiving adjuvant CT. On multivariate Cox regression analysis, high risk tumors (hazard ratio [95% confidence interval] = 1.31 [1.25-1.38]) and lack of adjuvant chemotherapy (1.25 [1.09-1.44]) were associated with worse overall survival (OS). Additionally, male sex, age ≥ 60 years, higher comorbidity burden, lack of insurance, low facility volume, low median income, non-squamous histology were associated with worse OS. After propensity score matching, Kaplan-Meier survival analysis of the high risk subgroup (n = 2923) showed a significant difference in overall survival (OS) between those who received adjuvant CT (n = 1032, 5 year OS, 74.7%; 95% CI, 70.9%-78.0%) and those who did not (n = 1891, 5 year OS, 66.9%; CI, 63.9%-69.6%; p = 0.0002). In patients with no high risk factors for recurrence (n = 384), OS was not significantly different between the patients who received adjuvant CT (n = 78, 5 year OS, 75.8%; CI, 61.3%-85.5%) and those who did not receive adjuvant CT (n = 306, 5 year OS, 77.1%; CI, 70.0%-82.7%; p = 0.3). Conclusions: Our study showed better survival with adjuvant CT in patients with pathological stage I NSCLC who have tumor size greater than 2 cm, LVI and/or VPI.

Does chemotherapy affect survival of breast cancer (BC) patients with recurrence score 26-30?

523 Background: The Oncotype-DX recurrence score (RS) allows providers to identify hormone receptor positive and HER2-negative breast cancer (BC) patients that may benefit from adjuvant chemotherapy (AC). The TAILORx Trial showed no benefit of AC among patients with RS of 11-25, except for patients younger than 50 years. There are, however, limited studies examining any benefit of AC among those with RS of 26-30. We sought to examine the effect of AC on BC-specific survival among these patients utilizing a national database. Methods: We queried the Surveillance, Epidemiology, and End Results database for newly diagnosed female BC patients between 2010-2015. We included patients with T1-T3, hormone receptor positive, HER2-negative, and lymph node-negative BC with RS of 26-30. Patients with tumors 5 mm or less and with incomplete records were excluded. Cox Proportional-Hazards Model was done to examine the effect of AC on BC-specific survival. A sub-group analysis was performed for patients younger than 50 years to examine the effect of AC on BC-specific survival. Results: We included 2,982 patients, of whom 1,686 (56.5%) received AC. Administration of AC was associated with lower age (56.5 [9.2] vs 61.8 [9.7], p &lt; 0.001), Grade III&amp;IV (39.7% vs 30.2%, p &lt; 0.001), married or patients with partners (66.5% vs 61.5%, p &lt; 0.001), and T stage &gt; 1 (31.3% vs 26.8%, p = 0.03). AC was not associated with insurance status, race, and histology. Overall 5-year BC-specific survival was 97.3% (96.2-98.3%). After adjustment through cox regression, AC was found to not have an effect on survival (HR: 0.54 [0.27-1.10], p = 0.09). There were 579 (19.4%) patients that were younger than 50 years, and AC did not have an effect on survival among these patients (HR: 0.44 [0.08-2.44], p = 0.35). Similarly, among the 2,403 (80.6%) patients aged 50 or older, AC did not have an effect on survival (HR: 0.49 [0.22-1.11], p = 0.09). Conclusions: In this retrospective analysis, administration of AC was associated with lower age, higher grade, marital status, and T stage. AC did not affect BC-specific survival among patients with a RS of 26-30. Subgroup analysis did not show any benefit of AC among patients younger than 50 years or among those 50 or older. Further prospective randomized trials are warranted to identify sub-groups that may potentially benefit from AC.

Adjuvant chemotherapy impact on the overall survival of completely resected small bowel adenocarcinoma: An updated meta-analysis.

e16806 Background: While the small intestine represents around 75% of the length and more than 90% of the gastrointestinal tract mucosal surface, it contributes around 2% of gastrointestinal tumors. Adenocarcinoma which constitutes 40% of all small bowel tumors is the most common histology. Complete surgical resection of early-stage small bowel adenocarcinoma (SBAC) is the only proven potentially curative therapy. Due to the rarity of this disease and the absence of randomized trials, the benefit of postoperative adjuvant chemotherapy (ACT) in patients with completely resected localized SBAC has been controversial. A meta-analysis conducted in 2018 found no survival benefit for adjuvant therapies in SBAC. However, this meta-analysis combined studies that used adjuvant chemotherapy and chemoradiotherapy and included studies contaminated by other less chemosensitive histologies and more advanced and sometimes metastatic disease. The purpose of this meta-analysis is to evaluate the impact of ACT on the overall survival (OS) of patients with completely resected SBAC incorporating more recent studies. Methods: A review of the medical literature was conducted using online databases. Inclusion criteria consisted of resected small bowel adenocarcinoma, English language, publications from 2000 to the present, and comparative studies reporting OS with hazard ratios (HR) or Kaplan-Meier curves of patients that underwent ACT versus those that did not. Adjuvant chemoradiotherapy studies and those that reported aggregate OS for a cohort with mixed histologies were excluded. A meta-analysis was conducted using an inverse variance method with a random-effects model. Results: Nine retrospective series which included 2082 patients were selected and analyzed. The majority of SBAC patients that received ACT belonged to stages II &amp; III. ACT was found to be significantly associated with better OS in patients with completely resected SBAC (HR 0.66, 95%CI: 0.56-0.78, p &lt; 0.001). Conclusions: This is the first meta-analysis to show that adjuvant chemotherapy is associated with a survival benefit in patients with completely resected small bowel adenocarcinoma. In the absence of randomized clinical trials, this meta-analysis represents the most compelling data supporting the use of ACT in this patient population.

Adjuvant chemotherapy with or without an anthracycline in older adults with node-negative triple-negative breast cancer (TNBC): A SEER Medicare study.

e12505 Background: TNBC is an aggressive breast cancer subtype comprising approximately 15% of breast cancers. Adjuvant chemotherapy reduces the risk of recurrence, particularly in patients with tumors &gt; 1 cm or node positive disease. Anthracycline (A) + taxane (T)-containing regimens are more efficacious than T-based regimens, however, the risk of cardiac toxicity is greater in older patients. We investigated the use of AT and T-containing regimens in patients ≥ 66 years old with node negative TNBC and evaluated clinical outcomes and cardiac risk factors. Methods: We identified female patients ≥ 66 diagnosed between 2010-2015 with TNBC node negative disease in the Surveillance, Epidemiology, and End Results (SEER) Medicare database. Baseline characteristics, including age, tumor size, cardiac history, and adjuvant chemotherapy administration (AT vs. T) were collected. A logistic regression analysis was performed to estimate independent predictors of AT vs. T chemotherapy. Overall survival (OS) was estimated at 3 years. Results: We identified 3348 patients, including 1679 (50.2%) who received chemotherapy for T1a/bN0 (32.5%), T1cN0 (55.5%), T2N0 (57.0%) and T3/T4N0 (49.6%) disease. Of those, 984 (58.6%) received T, 420 (25.0%) received AT and 275 (16.4%) received other chemotherapy. AT use was associated with larger tumor size; T1a/bN0 (13.6%), T1cN0 (21.3%), T2N0 (31.6%) and T3/T4N0 (34.9%). In a multivariate analysis, independent predictors of AT vs. T were age, region treated in the USA, tumor size and presence of prior cardiac risk factors or pre-existing cardiac disease. OS at 3 years was 91% for T and 86% for AT (p 0.03). Conclusions: Approximately half of older patients diagnosed with node negative TNBC received adjuvant chemotherapy. T-based regimens were more commonly used than AT regimens. Younger age, higher stage and lack of cardiac comorbidities correlated with use of AT compared to T. Continued investigation of the benefit of adjuvant chemotherapy in older patients may assist in clinical decision making.