Adjuvant Multiagent Chemotherapy Research Articles

Predictors and benefits of multiagent chemotherapy for pancreatic adenocarcinoma: Timing matters.

Adjuvant (A) multiagent chemotherapy (MC) is the standard of care for patients with pancreatic adenocarcinoma (PDAC). Tolerating MC following a morbid operation may be difficult, thus neoadjuvant (NA) treatment is preferable. This study examined how the timing of chemotherapy was related to the regimen given and ultimately the overall survival (OS). The National Cancer Databasewas queried from 2006 to 2017 for nonmetastatic PDAC patients who underwent surgical resection and received MC or single-agent chemotherapy (SC) pre- or postresection. Predictors of receiving MC were determined using multivariable logistic regression. Five-year OS was evaluated using the Kaplan-Meier and Cox proportional hazards model. A total of 12,440 patients (NA SC, n = 663; NA MC, n = 2313; A SC, n = 6152; A MC, n = 3312) were included. MC utilization increased from 2006-2010 to 2011-2017 (33.1%-49.7%;odds ratio [OR]: 0.59;p < 0.001). Younger age, fewer comorbidities, higher clinical stage, and larger tumor size were all associated with receipt of MC (all p < 0.001), but NA treatment was the greatest predictor (OR 5.18;95% confidence interval [CI]: 4.63-5.80; p < 0.001). MC was associated with increased median 5-year OS (26.0 vs. 23.9 months; hazard ratio [HR]: 0.92; 95%CI: 0.88-0.96) and NA MC was associated with the highest survival (28.2 months) compared to NA SC (23.3 months), A SC (24.0 months), and A MC (24.6 months; p < 0.001). Use and timing of MC contribute to OS in PDAC with an improved 5-year OS compared to SC. The greatest predictor of receiving MC was being given as NA therapy and the greatest survival benefit was the NA MC subgroup. Randomized studies evaluating the timing of effective MC in PDAC are needed.

Undifferentiated embryonal sarcoma of the liver in a 9-year-old girl

Undifferentiated embryonal sarcoma of the liver (UESL) is a rare adult neoplasm. The primary treatments for UESL are total surgical resection and adjuvant multiagent chemotherapy. The current study presents a case of UESL in a 9-year-old female with abdominal pain and fever as her first symptoms. A cystic mass with solid components was discovered on sonography and computed tomography (CT) imaging. The patient underwent tumor removal surgery in addition to a liver lobectomy on the right side. The pathologist reported a single-focal cystic solid mass confined to the liver with no capsular invasion, and the final diagnosis based on the immunohistochemistry (IHC) results was UESL. The patient received chemotherapy, and she is doing well eight months after surgery with no signs of recurrence. In conclusion, large cystic hepatic lesions should be considered in the differential diagnosis. Despite the poor prognosis of UESL, aggressive surgical resection should be the most important factor in ensuring long-term survival.

Adjuvant chemotherapy for patients with locally advanced cervical carcinoma receiving definitive chemoradiation; utilization and outcomes before the OUTBACK trial (361)

Adjuvant chemotherapy for patients with locally advanced cervical carcinoma receiving definitive chemoradiation; utilization and outcomes before the OUTBACK trial (361)

A phase 3, randomized, open-label study of the anti-Globo H vaccine adagloxad simolenin/obi-821 in the adjuvant treatment of high-risk, early-stage, Globo H-positive triple-negative breast cancer.

TPS611 Background: Adagloxad simolenin (A-S) is an anti-Globo H immunogen comprised of the carbohydrate tumor antigen Globo H, covalently linked to keyhole limpet hemocyanin, a carrier protein that deploys T cells to enhance the humoral response. Administration of A-S in combination with the immune adjuvant OBI-821 serves as an anti-tumor associated carbohydrate antigen vaccine intended to generate anti-Globo H humoral responses in patients with Globo H-expressing tumors. Methods: Study OBI-822-011, a phase 3 study, was initiated in 2018. Following feedback from investigators and advisors the study design was changed from a double-blind, placebo-controlled study to an open-label, standard of care (SOC) study. The revised protocol includes patients who have recovered from surgery and completed all planned neoadjuvant and/or adjuvant multiagent chemotherapy and/or radiation therapy. SOC in the A-S/OBI-821 arm is concomitant therapy of capecitabine or immune checkpoint inhibitor. In the SOC arm patients will receive SOC therapy consisting of observation alone, or adjuvant capecitabine alone, or immune checkpoint inhibitor alone. The key protocol changes included a change from open-label to standard of care, providing unblinding and reconsent guidelines for patients enrolled into the study prior to the protocol amendment, allowing concurrent adjuvant single agent chemotherapy, revising the stratification algorithm from a non-hierarchical to a hierarchical structure and aligning the stratification factors with prognostic factors more representative of the study population, revising the eligibility criteria, number and frequency of assessments to reduce patient burden, revising the interim analysis timepoints for futility, and removed an interim analysis for superiority. Study Objectives: Primary Objective: To determine the effect of A-S/OBI-821 treatment on improving IDFS in the study population. Secondary Objectives: To determine the impact of A-S/OBI-821 treatment on Overall survival (OS), Quality of life (QoL), Breast cancer-free interval (BCFI), Distant disease-free survival (DDFS) in the study population; To determine the safety and tolerability of A-S/OBI-821 in the study population. Key Exploratory Objectives: Beyond the safety, efficacy, and QoL endpoints of this trial, exploratory endpoints will evaluate the relationship between aberrant Globo H expression and baseline characteristics, including tumor pathology and immune factors. Conclusion: An estimated 668 subjects will be enrolled, treated for up to 2 years, and followed until occurrence of 187 events (invasive disease recurrence or death) or 3 years from last subject randomized. Survival follow-up is for 5 years from randomization of last subject. Clinical trial information: NCT03562637.

Benefit for single-agent adjuvant chemotherapy in elderly patients with locally advanced gastric adenocarcinoma

Current NCCN guidelines exclude the possibility of using single-agent adjuvant chemotherapy in locally advanced gastric adenocarcinoma, while allowing doublet chemotherapy. However, single-agent adjuvant chemotherapy is a valid treatment option in other gastrointestinal malignancies, preferred for elderly and/or frail patients. The current study used a nationwide oncology database to assess the benefit of single-agent adjuvant chemotherapy, specifically in the elderly population. Using the National Cancer Database (2004-2016) we identified 1953 individuals with non-metastatic gastric adenocarcinoma who underwent upfront D2 gastrectomy with pathologic stage ≥ T3 or Npos and free surgical margins, and had not received either preoperative chemotherapy or pre-/postoperative radiotherapy. We used IPTW analysis to compare overall survival between individuals receiving either single- or multi-agent adjuvant chemotherapy, or referred to observation alone. Individuals receiving single-agent chemotherapy had an overall survival benefit compared with observation alone, with an HR of 0.70 (95% CI 0.55-0.88, p < 0.001). Individuals over the age of 65 had an OS benefit with an HR of 0.61 (95% CI 0.46-0.82, p < 0.001). Comparing individuals over the age of 65 receiving single- vs. multi-agent chemotherapy, there was no overall survival difference with an HR of 0.87 (95% CI 0.64-1.18, p = 0.38). Single-agent adjuvant chemotherapy with a fluoropyrimidine in locally advanced gastric adenocarcinoma following D2 gastrectomy can improve overall survival in elderly patients. Clinicians may consider using either capecitabine or 5-FU as a treatment option in the adjuvant setting for this age group.

Total Neoadjuvant Therapy Versus Standard Neoadjuvant Chemoradiation in Patients with Locally Advanced Rectal Cancer: A Comparison of Short- and Long-term Oncologic Outcomes.

To evaluate the impact of neoadjuvant multi-agent systemic chemotherapy and radiation (TNT) vs neoadjuvant single-agent chemoradiation (nCRT) and multi-agent adjuvant chemotherapy on overall survival (OS), tumor downstaging, and circumferential resection margin (CRM) status in patients with locally advanced rectal cancer. Outside of clinical trials and small institutional reports, there is a paucity of data regarding the short and long-term oncologic impact of TNT as compared to nCRT. Adult patients with stage II-III rectal adenocarcinoma were identified in the National Cancer Database [2006-2015]. Out of 8,548 patients, 36% received TNT and 64% nCRT. In the cohort, 13% had a pCR and 20% a neoadjuvant rectal (NAR) score <8. In multivariable analysis, as compared to nCRT, TNT demonstrated numerically higher pCR rates ( P = 0.05) but had similar incidence of positive CRM ( P = 0.11). Similar results were observed with NAR scores <8 as the primary endpoint. After adjusting for confounders, OS was comparable between the 2 groups. Additional factors independently associated with lower OS included male gender, uninsured status, low income status, high comorbidity score, poorly differentiated tumors, abdominoperineal resection, and positive surgical margins (all P <0.01). In separate models, both pCR and a NAR score <8 were associated with improved OS. In this national cohort, TNT was not associated with better survival and/or CRM negative status in comparison with nCRT, despite numerically higher downstaging rates. Further refinement of patient selection and treatment regimens are needed to establish effective neoadjuvant platforms to improve outcomes of patients with rectal cancer.

Role of brachytherapy in stage III endometrial cancer treated with adjuvant chemotherapy: Identifying factors predictive of a survival benefit

To determine which patients with stage III endometrial cancer receiving adjuvant chemotherapy derive benefit from the addition of vaginal brachytherapy, as stage III is a highly heterogeneous population with substantial variations in practice. Patients with FIGO stage III endometrial carcinoma diagnosed 2004-2016 who underwent at least total hysterectomy and adjuvant multiagent chemotherapy were identified in the National Cancer Database. The primary outcome was overall survival according to receipt of brachytherapy, stratified by histologic type, pathological features, and status of pelvic external beam radiotherapy (EBRT), and analyzed using the Kaplan-Meier method and Cox multivariable regression. In total, 9369 patients were identified (24% stage IIIA, 5% stage IIIB, 71% stage IIIC; 61% endometrioid, 39% nonendometrioid histology), and 28% received brachytherapy. In the endometrioid cohort, brachytherapy was associated with a 5% absolute increase in 3-year overall survival (87% vs. 82%, p < 0.0001), which persisted in multivariable analysis (adjusted hazard ratio 0.74, 95% confidence interval 0.64-0.84, p < 0.0001). The benefit of brachytherapy was greater in patients not also receiving EBRT, and in patients with vaginal/parametrial extension, grade 3 disease, lymphovascular invasion, and/or deep myometrial invasion. In the nonendometrioid cohort, brachytherapy was associated with a significant survival benefit in univariable but not multivariable analysis, regardless of EBRT status or pathological features. Factors predictive of brachytherapy benefit were endometrioid histology and pathological risk factors for local recurrence. Additionally, brachytherapy appeared more beneficial in patients not already receiving pelvic EBRT. Further research is warranted to determine which stage III patients may be best served by brachytherapy, EBRT, or both.

Adjuvant Chemotherapy for T4 Non-Small Cell Lung Cancer with Additional Ipsilateral Lung Nodules

BackgroundAdjuvant chemotherapy is indicated for patients with resectable stage II and IIIa non-small cell lung cancer. With the revised definition of T4 tumors with nodules in a different ipsilateral lobe, the survival advantage imparted by adjuvant chemotherapy has yet to be defined. We evaluated the role of adjuvant chemotherapy in patients with T4 disease characterized by additional tumor nodules in a different ipsilateral lobe treated with surgical resection. MethodsWe identified patients with T4 disease and additional tumor nodules in a different ipsilateral lobe treated with surgical resection alone or with adjuvant chemotherapy in the National Cancer Database between 2010 and 2016. The primary outcome was 3-year overall survival (OS). ResultsA total of 920 patients with T4 tumors and additional tumor nodules in a different ipsilateral lobe were identified. We excluded patients with lymph node metastases, tumors 4 cm or greater, and local invasion. Of the remaining 373 patients, 152 received surgery and adjuvant multiagent chemotherapy whereas 221 received surgery alone. When adjusted for patient, tumor, and treatment factors, the use of adjuvant chemotherapy was associated with improved 3-year OS compared with surgery alone (hazard ratio = 0.572; 95% confidence interval, 0.348-0.940; P = .03). ConclusionsAdjuvant chemotherapy in patients with T4 non-small cell lung cancer with additional tumor nodules in a different ipsilateral lobe is associated with improved 3-year OS. Accurate identification of T4 disease is important to define patients in whom adjuvant chemotherapy should be considered. Further prospective study is needed to delineate further the use of adjuvant chemotherapy for this patient population.

Survival outcomes of adjuvant chemotherapy in elderly patients with stage III colon cancer.

89 Background: The survival impact of multi-agent (MAC) as compared to single-agent (SAC) adjuvant chemotherapy (AC) in elderly patients with stage III colon cancer (CC) remains controversial. The aim of this study is to evaluate the survival outcome comparing MAC to SAC in this population utilizing the National Cancer DataBase (NCDB). Methods: Patients 70 years and older with pathological stage III CC were identified between 2004 and 2015 from the NCDB using ICD-O-3 morphology and topography codes: 8140-47, 8210-11, 8220-21, 8260-63, 8480-81, 8490, and C18.0-18.8 (without C18.1). Univariate and multivariable analyses were conducted and Kaplan-Meier analysis and Cox proportional hazard models were used to identify the association between MAC vs. SAC and overall survival (OS). Results: A total of 41,707 elderly patients (≥70 years old) with stage III CC were identified. Around half of the patients (n = 20,257; 48.5%) received AC; the majority of whom (n = 12,923, 63.8%) received MAC. The median age was 79 (range 70-90). Of the patients who received AC, the majority were female (n = 11,201, 55.3 %), Caucasians (87.4%) and had a moderately differentiated tumor grade (n = 12,619, 62.3%). Tumor size more than 4 cm was identified in 11,785 (58.2%) patients and 18,496 (91.3%) had negative surgical margins. Low-risk stage III CC constituted 50.6% (n = 10,264) of the study population. High-risk stage III CC was associated with worse OS compared to low-risk disease (p &lt; 0.001). MAC was associated with better 5-year OS compared to SAC (p &lt; 0.001). High-risk stage III patients who received MAC had an OS of 4.2 v. 3.4 years in SAC (p &lt; 0.001). In low risk stage III, patients who received MAC had median OS of 8.5 v. 7 years in SAC (p &lt; 0.001). In Univariate, male sex, positive surgical margin, insurance and facility types, age, year of diagnosistumor size, and Charlson-Deyo Score of &gt; 2 were associated with worse OS (p &lt; 0.05). Conclusions: Multi-agent AC is associated with better survival in stage III CC patients 70 years and older compared to SAC. Enhanced benefit of MAC was shown for both low risk and high risk stage III CC.

Time to surgery in patients with locoregional pancreatic ductal adenocarcinoma followed by adjuvant therapy does not significantly impact overall survival or rate of R0 resection

Presenter: Lyonell Kone MD, MHS | University of Illinois at Chicago Background: In the present COVID-19 pandemic, many pancreatic ductal adenocarcinoma (PDAC) patients have experienced delayed time to definitive surgery raising concerns that it will translate into worse outcomes. Given the rapid progression of this disease, it is often deemed necessary to minimize time to surgery. There is limited evidence to recommend optimal time-frames, however, prospective evaluation is restricted by ethical considerations. Therefore, we aim to utilize a large well powered cancer database to evaluate the impact of time to surgery on survival and rate of R0 resection (negative margins). Methods: Patients with locoregional PDAC diagnosed between 2004-2017 undergoing surgery-first sequence followed by adjuvant therapy were identified through the National Cancer Database. Time from diagnosis to surgery was evaluated and stratified a priori into five groups: less or equal to 2 weeks (Strata A), 2 weeks to 1 month (Strata B), 1 to 2 months (Strata C), 2 to 3 months (Strata D), 3 to 6 months (Strata E), greater than 6 months (Strata F). Survival analysis was performed with both Kaplan-Meyer Curves, Log-rank and Cox regression analysis. Rate of R0 resection was analyzed with logistic regression. Results: A total of 18,245 patients with locoregional PDAC underwent a surgery-first approach, and all patients in the analysis received adjuvant chemotherapy. On univariate analysis, there was no difference in overall survival (m-OS: A= 22, B=23, C=22, D=22, E=25, F=25 weeks; log-rank: p=0.640) between different time strata (Figure 1). However, there was a trend towards increased rate of R0 resections with increasing time to surgery (A=76%, B=78%, C=77%, D=79%, E=80%, F=81%; X2: p=0.050). After adjusting for age, gender, race, co-morbidities, clinical stage, hospital type, tumor location, and receipt of multi-agent adjuvant chemotherapy, there were no differences in survival (cox regression: p=0.386), but there was a trend towards increased rates of R0 resections (Logistic regression: p=0.044). Conclusion: In patients with locoregional PDAC undergoing surgery-first with adjuvant therapy, the time from diagnosis to surgery was not independently associated with overall survival or with the rate of R0 resection. Despite the inherent limitations of this dataset, this result indicates that the driver of patient survival is likely the underlying tumor biology, and that a surgery-first approach may still be appropriate if time to surgery has to be delayed beyond average, as long as the patient remains a candidate for surgery.

Adjuvant Radiotherapy Improves Overall Survival When Added to Surgery and Chemotherapy for Endometrial Carcinosarcoma: A Surveillance, Epidemiology, and End Results Analysis

Endometrial carcinosarcoma (CS), or malignant mixed Mullerian tumor, is a high-grade variant of endometrial carcinoma with a high risk for recurrence. Adjuvant multi-agent chemotherapy (CHT) is a preferred treatment modality in all stages of disease, with or without radiotherapy (RT). As prospective data are lacking regarding the benefit of RT when added to adjuvant CHT in CS, we sought to analyze the Surveillance, Epidemiology, and End Results (SEER) database to ascertain whether RT improves overall survival (OS) and cancer-specific survival (CSS) when added to surgery and CHT for endometrial CS. SEER 18 Custom Data registries (Nov 2018 submission) were queried for endometrial (ICD10 C54.1-9, C55.9) CS (ICD-0-3 8980-3). Patients with stage I-III CS who received CHT with or without RT were included for analysis. Univariate analysis (UVA) and multivariable analysis (MVA) using Kaplan-Meier and Cox proportional hazards regression modeling were performed. Propensity-score matched analysis with inverse probability of treatment weighting was performed to account for indication bias. Furthermore, conditional landmark analysis using a minimum follow-up time of 3 months was performed to minimize immortal time bias. A total of 1,541 patients treated from 1988-2016 were included in this analysis. Median age at diagnosis was 65 (IQR 59-71). Patients had FIGO stage IA (30%), IB (14%), II (9%), IIIA (8%), IIIB (3.6%), or IIIC (32%) disease. All patients received CHT and 54% received RT, either with external beam RT (EBRT) alone (25%), EBRT with a brachytherapy boost (9.7%), or brachytherapy alone (18.7%). On UVA, adjuvant RT improved OS (HR 0.65, 95% CI 0.56-0.77, p<0.001) and CSS (HR 0.64, 95% CI 0.54-0.76, p<0.001) compared to surgery and CHT alone. Of note, RT was more likely to be delivered to patients who were slightly younger (p = 0.034) and to those with a lower FIGO stage (p<0.001). After adjusting for these baseline imbalances, the OS benefit provided by adjuvant RT persisted (HR 0.76, 95% CI 0.65-0.89, p<0.001), as did the CSS benefit (HR 0.74, 95% CI 0.63-0.87, p<0.001). Moreover, these findings were maintained using a 3-month conditional landmark analysis (HR 0.67, 95% CI 0.57-0.79). On subgroup analysis, factors associated with an OS benefit included stage IA (HR 0.45, 95% CI 0.45-0.99) and IIIA (HR 0.42, 95% CI 0.24-0.74) disease, grade III disease (HR 0.78, 95% CI 0.61-0.99), ages 50-64 years (HR 0.76, 95% CI 0.59-0.98) and ≥65 years (HR 0.79, 95% CI 0.64-0.98), and treatment delivered between 2010-2016 (HR 0.65, 95% CI 0.52-0.81). In patients with FIGO stage I-III endometrial CS undergoing surgery and CHT, RT improves OS and CSS. Further prospective data are needed to investigate the benefit of RT in endometrial CS treated with modern therapies.

Survival outcome of adjuvant chemotherapy in deficient mismatch repair stage III colon cancer.

The prognostic impact of DNA mismatch repair (MMR) status remains controversial in patients with stage III colon cancer who are treated with adjuvant chemotherapy (AC). The aim of this study was to evaluate the survival outcome of AC in deficient mismatch repair (dMMR)/microsatellite instable (MSI) stage III CC. Patients with pathological stage III CC between 2010 and 2013 were identified from the National Cancer Database using International Classification of Diseases for Oncology (3rd Edition) morphology and topography codes 8140, 8480, and C18.0-18.8. Patients with pathologic stage T3N2, T4N1, or T4N were considered high risk; patients with stage T3N1 were considered low risk. Univariate and multivariable analyses were conducted, and Kaplan-Meier analysis and Cox proportional hazards models were used to identify the association between AC and overall survival (OS). A total of 9226 patients with pathological stage III CC were identified, of which 2384 (25.8%) were MSI-high (MSI-H) and met the inclusion criteria of the final analysis. MSI-low (MSI-L) patients (n=6842) were excluded. There was a preponderance of women (55.0% [n=1311]), and 76.6% (n=1825) of patients were non-Hispanic white. The median age was 65 years (range, 19-90 years). The primary sites were the cecum (29.7% [n=707]), ascending colon (26.0% [n=620]), sigmoid colon (17.2% [n=410]), and transverse colon (10.8% [n=257]). The most common tumor grade was moderately differentiated (n=50.4% [1202]), followed by poorly differentiated (34.1% [n=813]) and well differentiated (5.1% [n=121]). High-risk pathologic stage III CC (T4N1, TxN2) constituted 51.0% (n=1215) of the study population. High-risk stage III was associated with worse OS compared with low-risk stage III on univariate (P<.001) analysis and displayed a similar trend on multivariable analysis, without a statistically significant difference. Multiagent AC was associated with improved OS compared with no treatment on univariate (P<.001) and multivariable (P<.001) analysis. When stratified by risk status, multiagent AC was associated with improved OS compared with no treatment for high-risk (P<.001) and low-risk (P<.001) stage III disease. Adjuvant chemotherapy is associated with better OS in stage III dMMR/MSI-H CC. An enhanced benefit was shown for high-risk stage III disease.

Disparities in Guideline-Concordant Treatment for Pathologic N1 Non-Small Cell Lung Cancer

Socioeconomic status (SES) disparities in the surgical management of patients with non-small cell lung cancer (NSCLC) are well described. Disparities in the receipt of adjuvant chemotherapy are poorly understood. We assessed the influence of SES on adjuvant chemotherapy after resection in patients with pN1 NSCLC. The National Cancer Database was queried for cN0/N1 NSCLC patients who underwent surgical resection and had demonstrated pN1 disease. This cohort was further divided into those who received multiagent adjuvant chemotherapy (MAAC) vs surgery-only treatment. Factors associated with treatment assignment were examined, and long-term survival was compared. Of the 14,892 patients who underwent resection for pN1 disease, 8061 (54.1%) received MAAC. Patients were less likely to receive MAAC if they resided in rural areas (odds ratio, 1.23; 95% confidence interval [CI], 1.11-1.37; P < .001), or were uninsured or on Medicaid (odds ratio, 1.23; 95% CI, 1.07-1.41; P= .004). The propensity score-weighted 5-year survival was significantly higher for those receiving MAAC compared with surgery only (53.6% vs 39.5%, log-rank P < .001). Lower income (hazard ratio, 1.06; 95% CI, 1.00-1.12; P= .044) and uninsured or Medicaid insurance status (hazard ratio, 1.22; 95% CI, 1.13-1.31; P < .001) were independently associated with increased mortality by Cox regression in the propensity score-weighted cohort. pN1 NSCLC patients living in rural areas or who are uninsured or on Medicaid insurance are at increased risk of not receiving MAAC. Treatment with MAAC significantly improves long-term survival of pN1 patients. Efforts should be made to ensure these at-risk groups receive guideline-concordant care.

Utilization of Adjuvant Radiotherapy for Resected Colon Cancer and Its Effect on Outcome.

Adjuvant radiation is generally not recommended for colon cancer but may be considered in certain clinical scenarios [advanced local disease (pT4) and/or positive margins]. Guidelines in this area are lacking; thus we analyzed the National Cancer Database (NCDB) for patterns of care in this regard and any predictors for outcome. We queried the NCDB from 2004 to 2016 for patients with resected adenocarcinoma of the colon having pT4 and/or had positive margins on final pathology and who received adjuvant multiagent chemotherapy. Multivariable logistic regression was used to identify predictors of adjuvant radiation. A propensity score was used to perform matched Kaplan-Meier analysis. Propensity-adjusted Cox regression was used to identify predictors of overall survival. We identified 23,325 patients meeting criteria, of whom 1711 (7%) received adjuvant radiation. Median follow-up was 36months. The majority of patients were pT4 alone (65%). Predictors of adjuvant radiation were lower comorbidity score, younger age, more remote year of treatment, and both pT4 and positive margins. Kaplan-Meier analysis revealed improved overall survival (OS) in patients with both pT4 and positive margins treated with radiation (median OS: 66 versus 47months, p = 0.02). Receipt of adjuvant radiation was associated with improved OS [hazard ratio (HR): 0.86 (0.80-0.93) p = 0.0002] on Cox regression analysis. Increased age, higher comorbidity score, lower income, government insurance, and combined pT4/positive margins were indicative of worse survival. Expectedly, adjuvant radiation use was relatively low but was associated with improved OS in patients with both pT4 and positive margins.

Sociodemographic Disparities in the Receipt of Adjuvant Chemotherapy Among Patients With Resected Stage I-III Pancreatic Adenocarcinoma.

Adjuvant therapy for resected pancreatic adenocarcinoma was given a category 1 NCCN recommendation in 2000, yet many patients do not receive chemotherapy after definitive surgery. Whether sociodemographic disparities exist for receipt of adjuvant chemotherapy is poorly understood. The National Cancer Database was used to identify patients diagnosed with nonmetastatic pancreatic adenocarcinoma who underwent definitive surgery from 2004 through 2015. Multivariable logistic regression defined the adjusted odds ratio (aOR) and associated 95% CI of receipt of adjuvant chemotherapy. Among patients receiving chemotherapy, multivariable logistic regression assessed the odds of treatment with multiagent chemotherapy. Among 18,463 patients, 11,288 (61.1%) received any adjuvant chemotherapy. Sociodemographic factors inversely associated with receipt of any adjuvant chemotherapy included uninsured status (aOR, 0.61; 95% CI, 0.50-0.74), Medicaid insurance (aOR, 0.66; 95% CI, 0.57-0.77), and lower income (P<.001 for all income levels compared with ≥$46,000). Black race (aOR, 0.72; 95% CI, 0.57-0.90) and female sex (aOR, 0.75; 95% CI, 0.65-0.86) were associated with lower odds of receiving multiagent chemotherapy. There was a statistically significant interaction term between black race and age/comorbidity status (P=.03), such that 26.4% of black versus 35.8% of nonblack young (aged ≤65 years) and healthy (Charlson-Deyo comorbidity score 0) patients received multiagent adjuvant chemotherapy (P=.006), whereas multiagent adjuvant chemotherapy rates were similar among patients who were not young and healthy (P=.15). In this nationally representative study, receipt of adjuvant chemotherapy appeared to be associated with sociodemographic characteristics, independent of clinical factors. Sociodemographic differences in receipt of adjuvant chemotherapy may represent a missed opportunity for improving outcomes and a driver of oncologic disparities.

Defining the survival benefit of adjuvant pelvic radiotherapy and chemotherapy versus chemotherapy alone in stages III-IVA endometrial carcinoma

ObjectivesTo determine which patients with locoregionally advanced endometrial cancer may benefit from pelvic external beam radiotherapy (EBRT) in addition to chemotherapy compared to chemotherapy alone. MethodsPatients with FIGO stages III–IVA endometrial carcinoma between 2004 and 2016 who underwent at least total hysterectomy and adjuvant multiagent chemotherapy were identified in the National Cancer Database. The primary outcome was overall survival according to receipt of pelvic EBRT, analyzed using the Kaplan-Meier method and Cox multivariable regression. ResultsIn total, 13,270 patients were identified (62% pure endometrioid, 38% serous/clear cell or mixed histology; 22.6% stage IIIA, 4.7% stage IIIB, 71.2% stage IIIC, 1.5% stage IVA), of whom 40% received pelvic EBRT. In univariable analysis, EBRT was associated with absolute 5-year survival increases of 5% and 9% in the endometrioid and non-endometrioid cohorts, respectively (P < 0.0001). In multivariable analyses stratified by stage and histology, patients with a significant benefit from EBRT were stage IIIC (specifically IIIC2) endometrioid (adjusted hazard ratio [HR] 0.73, P = 0.01) and stages IIIB and IIIC non-endometrioid (adjusted HR 0.52, P = 0.01 and adjusted HR 0.79, P < 0.0001). The benefit of EBRT in node-positive patients persisted in those who underwent more extensive lymphadenectomy. ConclusionsStages III–IVA endometrial cancer comprised a heterogeneous population with respect to the added benefit of radiotherapy compared to chemotherapy alone. Patients with stage IIIC2 endometrioid and stages IIIB–C non-endometrioid cancer may be most likely to benefit from pelvic EBRT.

Survival Benefit Persists With Delayed Initiation of Adjuvant Chemotherapy Following Radical Cystectomy for Locally Advanced Bladder Cancer

ObjectiveTo determine if delaying the initiation of adjuvant chemotherapy following radical cystectomy for locally advanced bladder cancer worsens overall survival. MethodsThis is a retrospective cohort study utilizing the National Cancer Database from 2006 to 2013. We included treatment-naïve patients who underwent radical cystectomy for muscle-invasive bladder cancer found to have locally advanced disease (pT3-T4 and/or pN+). Patients received no chemotherapy or multiagent adjuvant chemotherapy between 30 and 180 days following surgery. We used a multivariable Cox Regression to assess for differences in overall survival according to when patients initiated adjuvant chemotherapy. ResultsWe identified 3590 patients: 2581 received no chemotherapy and 1009 received multiagent adjuvant chemotherapy. Adjuvant chemotherapy began 31-60 days postsurgery in 538 patients, 61-90 days in 321 patients, and 91-180 days in 150 patients. Relative to patients who did not receive chemotherapy, adjuvant chemotherapy decreased mortality when started 31-60 days (hazard ratio [HR], 0.60; 95% confidence interval [CI], 0.52-0.69; P <.001), 61-90 days (HR, 0.62; 95% CI, 0.53-0.74; P <.001), and 91-180 days following radical cystectomy (HR, 0.69; 95% CI, 0.55-0.87; P = .002). ConclusionAdjuvant chemotherapy offers a survival benefit when started up to 6 months after radical cystectomy in patients with high-risk disease who did not receive neoadjuvant chemotherapy. Patients who require delayed initiation of adjuvant chemotherapy can still benefit from treatment.

Refining the role of adjuvant chemotherapy in stage IB and IIA NSCLC.

8519 Background: The role of adjuvant chemotherapy (AC) in stage IB (pT2aN0) and IIA (pT2bN0) non-small cell lung cancer (NSCLC) is currently unclear. Existing guideline recommendations are inconsistent, ranging from all tumors &gt;4 cm, to any patient with “high-risk features” (visceral pleural invasion (VPI), lymphovascular invasion (LVI), high grade, or sublobar resection). We used the National Cancer Data Base (NCDB) to clarify the role of AC in pT2N0 patients. Methods: The NCDB was queried for treatment-naïve, post-R0 resection, pT2N0 (AJCC 8th edition) NSCLC patients between 2010 &amp; 2014. Patients treated with single-agent AC were excluded. Survival was calculated from 30 days after surgery to minimize immortal time bias. Multivariable Cox proportional hazards regression was used to estimate the association between AC and survival across tumor sizes (T2a: 3-4 cm and T2b: 4-5 cm to reflect guideline stratifications) and risk features. Results: Of the 10,127 patients identified, 1,856 (18%) received multi-agent AC. AC patients tended to be younger (median age 64 vs 70 yrs, p&lt;0.001), privately insured (40% vs 24%, p&lt;0.001), treated at a non-academic center (71% vs 66%, p&lt;0.001), and comorbidities-free (53% vs 48%, p&lt;0.001). In T2a patients (N=6,699), AC was not significantly associated with a mortality reduction, regardless of the presence of any high-risk features. In T2b patients (N=3,428), AC (N=931, 27%) was associated with a lower mortality (HR 0.77, 95% CI 0.65-0.9, p=0.001). However, in the absence of any high-risk features (N=1414, 41% of the 4-5 cm cohort), AC was not significantly associated with survival benefit (Table). Conclusions: The presence of high-risk features does not appear to support the guideline recommendations regarding the use of AC in stage IB patients with 3-4 cm tumors. On the other hand, the benefit of AC for 4-5 cm tumors may be limited to patients with at least one high-risk feature. [Table: see text]

Racial disparities in the receipt of adjuvant chemotherapy in patients with resected stage I-III pancreatic adenocarcinoma.

357 Background: Adjuvant chemotherapy for resected pancreatic adenocarcinoma is a category 1 NCCN recommendation, however studies have shown that many patients do not go on to receive chemotherapy after definitive surgery. Whether racial disparities exist for receipt of adjuvant chemotherapy is unknown. Methods: The National Cancer Database was used to identify 28,255 patients with non-metastatic pancreatic adenocarcinoma who underwent definitive surgery between 2005-2014. Multivariable logistic regression defined adjusted odds ratio (AOR) and 95% confidence intervals (CI) of receipt of adjuvant chemotherapy by race. Additional variables included in the model were age, sex, stage, node positivity, comorbidity index, facility type and insurance. Among those receiving chemotherapy, multivariable logistic regression assessed odds of treatment with multiagent chemotherapy and among those not receiving chemotherapy, predictors of chemotherapy refusal were assessed. Results: Compared to white patients, black patients were less likely to receive adjuvant chemotherapy (AOR 0.74, 95% CI 0.64-0.85, p &lt; 0.001) and multiagent adjuvant chemotherapy (AOR 0.80, 95% CI 0.72-0.88, p &lt; 0.001). The disparities were limited to patients with comorbidity score of 0 and persisted when analyses were restricted to only academic cancer centers. Among 2,405 patients not treated with chemotherapy, black patients had lower odds of refusing chemotherapy (AOR 0.72, 95% CI 0.55-0.93, p = 0.01). Conclusions: In this nationally representative study, black patients were less likely to receive NCCN-guideline concordant treatment for resected pancreatic adenocarcinoma; this disparity did not appear to be driven by increased refusal of treatment by black patients. Given that differences in quality of care may contribute to disparities in cancer survival, our findings suggest that outcomes for black patients could be improved by increasing the proportion receiving guideline-concordant adjuvant chemotherapy. Further investigation is needed to identify factors leading to the observed differences in this study, such that appropriate interventions can be undertaken to mitigate this disparity.

Effectiveness of adjuvant chemotherapy in patients with Stage II colorectal cancer: A multicenter retrospective study.

Background:Adjuvant chemotherapy (ACT) for patients with Stage II colorectal cancer (CRC) is an area of controversy in oncology. International guidelines recommend the use of ACT in patients with specific high-risk features. This study aimed to investigate the effectiveness of ACT in improving survival in patients with and without high-risk features.Materials and Methods:A total of 225 patients with Stage II CRC who underwent primary tumor resection were included in this study. Patients with one or more high-risk features including T4 tumor, poor differentiation, lymphovascular invasion, perineural invasion, bowel obstruction, local perforation, positive resection margins, or suboptimal lymph node sampling (fewer than 12 nodes) were classified as high risk. The survival analysis was performed between patients who only received curative surgery and those received single-agent (5-fluorouracil [5-FU] and leucovorin [LV] or capecitabine) or multiagent ACT (oxaliplatin and 5-FU + LV or oxaliplatin and capecitabine).Results:The 5-year overall survival (OS) rate was 88.4%, and the 5-year disease-free survival (DFS) rate was 80.4%. The 5-year OS and DFS rates improved insignificantly with ACT (89.8% vs. 81.2%, P = 0.59 and 81.3% vs. 74.6%, P = 0.41, respectively); however, multiagent ACT results to inferior 5-year OS and DFS compared to single-agent ACT (82.1 vs. 92.8%, P = 0.14 and 70.1% vs. 86%, P = 0.07, respectively). ACT was associated with insignificant improved OS and DFS in both high-risk and low-risk groups, but high-risk patients who received multiagent ACT had a significant inferior OS and DFS in comparison with those received single-agent ACT. T4 tumor and obstruction were independent poor prognostic factors affecting OS and DFS.Conclusion:In our population, the improvement of OS and DFS with ACT was not statistically significant in high-risk and low-risk patients with Stage II CRC.