Receipt Of Neoadjuvant Chemotherapy Research Articles

Predictors of pathological complete response to neoadjuvant treatment and changes to post-neoadjuvant HER2 status in HER2-positive invasive breast cancer

The response of human epidermal growth factor receptor2 (HER2)- positive breast cancer (BC) patients to anti-HER2 targeted therapy is significant. However, the response is not uniform and a proportion of HER2-positive patients do not respond. This study aims to identify predictors of response in the neoadjuvant treatment and to assess the discordance rate of HER2 status between pre- and post-treatment specimens in HER2-positive BC patients. The study group comprised 500 BC patients treated with neoadjuvant chemotherapy (NACT) and/or neoadjuvant anti-HER2 therapy and surgery who had tumours that were 3+ or 2+ with HER2 immunohistochemistry (IHC). HER2 IHC 2+ tumours were classified into five groups by fluorescence in situ hybridisation (FISH) according to the 2018 ASCO/CAP guidelines of which Groups 1, 2 and 3 were considered HER2 amplified. Pathological complete response (pCR) was more frequent in HER2 IHC 3+ tumours than in HER2 IHC 2+/HER2 amplified tumours, when either in receipt of NACT alone (38% versus 13%; p = 0.22) or neoadjuvant anti-HER2 therapy (52% versus 20%; p < 0.001). Multivariate logistic regression analysis showed that HER2 IHC 3+ and histological grade 3 were independent predictors of pCR following neoadjuvant anti-HER2 therapy. In the HER2 IHC 2+/HER2 amplified tumours or ASCO/CAP FISH Group 1 alone, ER-negativity was an independent predictor of pCR following NACT and/or neoadjuvant anti-HER2 therapy. In the current study, 22% of HER2-positive tumours became HER2-negative by IHC and FISH following neoadjuvant treatment, the majority (74%) HER2 IHC 2+/HER2 amplified tumours. Repeat HER2 testing after neoadjuvant treatment should therefore be considered.

Trends in neoadjuvant chemotherapy versus surgery-first in stage I HER2-positive breast cancer patients in the National Cancer DataBase (NCDB).

Neoadjuvant chemotherapy (NAC) is the standard of care for locally advanced HER2 + breast cancer (BC). Optimal sequencing of treatment (NAC vs. surgery first) is less clear cut in stage I (T1N0) HER2 + BC, where information from surgical pathology could impact adjuvant treatment decisions. Utilizing the NCDB, we evaluated the trend of NAC use compared to upfront surgery in patients with small HER2 + BC. We identified NCDB female patients diagnosed with T1 N0 HER2 + BC from 2010 through 2015. Prevalence ratios (PR) using multivariable robust Poisson regression models were calculated to measure the association between baseline characteristics and the receipt of NAC. Analysis of trends over time was denoted by annual percent change (APC) of NAC versus surgery upfront. Of the 14,949 that received chemotherapy and anti-HER2 therapy during the study period, overall 1281 (8.6%) received NAC and 13,668 (91.4%) received adjuvant treatment. Patients receiving NAC increased annually from 4.2% in 2010 to 17.3% in 2015, with the most rapid increase occurring between years 2013 (8.5%) and 2014 (14.2%). The greatest increase was seen in patients with cT1c tumors with an APC of 37.8% over the study period (95% CI 29.0, 47.3%, p < 0.01), although a significant trend was likewise seen in patients with cT1a (APC = 26.1%,95% CI 1.59, 56.6%), and cT1b (APC = 27.4%, 95% CI 18.0, 37.7%) tumors. Predictors of neoadjuvant therapy receipt were age younger than 50 (PR = 1.69, 95% CI 1.52, 1.89), Mountain/Pacific area (PR = 1.24, 95% CI 1.05, 1.46), and estrogen receptor negativity (ER- PR + : PR = 2.01, 95% CI 1.51, 2.68; ER- PR- : PR = 1.49, 95% CI 1.32, 1.69). Neoadjuvant therapy for T1 N0 HER2 + BC increased over the study period and was mostly due increased use in clinical T1c tumors. This may be consistent with secular change in Pertuzumab treatment following FDA approval in 2013.

Neoadjuvant Chemotherapy for Pancreatic Ductal Adenocarcinoma is Associated with Lower Post-Pancreatectomy Readmission Rates: A Population-Based Cohort Study.

Despite neoadjuvant chemotherapy (NAC) being increasingly utilized and possibly associated with improved oncological outcomes, the impact of NAC on textbook outcomes following pancreatectomy for pancreatic ductal adenocarcinoma (PDAC) remains debated. A retrospective review of the National Cancer Database of patients undergoing resection of non-metastatic PDAC from 2004 to 2016 was performed. Propensity score matching was used to account for treatment selection bias in patients with and without NAC (noNAC). A multivariable binary logistic regression model was used to analyze the association of NAC with length of stay (LOS), 30-day readmission, and 30- and 90-day mortality. Of 7975 (11%) NAC patients and 65,338 (89%) noNAC patients, 2911 NAC and 2911 noNAC patients remained in the cohort after matching. Clinicopathologic and demographic variables were well-balanced after matching. After matching, NAC was associated with significantly lower rates of 30-day readmission (5.5% vs. 7.4%; p=0.006), which remained after multivariable adjustment (odds ratio [OR] 0.74, 95% confidence interval [CI] 0.60-0.92; p=0.006). There were no significant differences in LOS and 30- and 90-day mortality in patients receiving NAC and noNAC. Stratified analyses by surgery type (i.e. pancreaticoduodenectomy [PD] and distal pancreatectomy [DP]) demonstrated consistent results. Receipt of NAC in PDAC patients undergoing DP or PD is associated with lower readmission rates and does not otherwise compromise short-term outcomes. These data reaffirm the safety of strategies incorporating NAC and is important to consider when devising policies aimed at quality improvement in achieving textbook outcomes.

Lymph node ratio is a reliable prognostic marker after neoadjuvant therapy and pancreaticoduodenectomy for pancreatic cancer, but does not predict the utility of adjuvant therapy

Presenter: Alexandra Adams MD, MPH | Brooke Army Medical Center Background: Neoadjuvant chemotherapy (NAT) has been increasingly utilized for patients with pancreatic ductal adenocarcinoma (PDAC). However, the role of additional adjuvant chemotherapy (AT) after NAT and surgical resection remains unclear. The lymph node ratio (LNR), defined as the number of positive nodes divided by total resected nodes, is a well-established prognostic indicator for patients with resected PDAC, and could potentially help decipher which patients could avoid AT after NAT. The objective of this analysis was to determine if LNR predicts survival benefit from receipt of AT following NAT and surgical resection. Methods: Patients who underwent pancreaticoduodenectomy after NAT from 2006-2017 and had pathologically node positive PDAC were identified using the National Cancer Database. Patients with metastatic disease or unknown lymph node status were excluded. Patients were grouped as receiving NAT plus AT, or NAT only. The LNR within the node-positive groups were compared, with a cutoff of 0.15. Five-year overall survival was determined by Kaplan-Meier analysis and multivariate (MV) Cox proportional hazards modeling. Results: A total of 1,182 patients were included: 623 patients with LNR=0.01-0.14 and 559 with LNR>=0.15. Median survival was higher among patients with LNR=0.01-0.14 than those with LNR>=0.15 (28.8 vs 20.5 months, log-rank p=0.15, receipt of additional AT was associated with improved median survival of 23.3 months vs 18.2 months without AT (log-rank p=0.0024). MV analysis by Cox proportional hazards revealed similar survival benefit from AT, with hazard ratios of 0.807 (95% CI 0.678-0.960, p=0.0156) for LNR=0.01-0.14 and 0.794 (95% CI 0.669-0.942, p=0.0084) for LNR>=0.15. Conclusion: Although LNR is a reliable prognostic indicator for PDAC, it does not predict the utility of AT after receipt of NAT. Thus, while LNR may be useful in counseling patients regarding prognosis, we advise against using it as a discriminator for decisions regarding adjuvant therapy. Further investigation is needed into the best selection criteria for patients that would benefit from additional AT after receipt of NAT and pancreaticoduodenectomy.

Recurrence, survival, and therapy-free interval after irreversible electroporation for pancreatic adenocarcinoma

Presenter: Wooil Kwon MD, PhD | Columbia University Background: Locally advanced pancreatic cancer (LAPC) is particularly challenging to treat. Systemic therapy may prolong survival but cannot offer a cure. Patients do not qualify for resection according to international guidelines, but accumulating experience from high volume centers in the modern era of chemotherapy suggest survival benefit in select patients undergoing resection. Recent efforts have focused on expanding surgical options. Irreversible electroporation (IRE) can be used to primarily control tumors in situ or to extend resection margins. This study provides valuable insight on survival, recurrence, and complications from a center that has integrated IRE into its treatment protocols. Methods: Data were collected for patients with T4 pancreatic ductal adenocarcinoma treated with IRE at a single tertiary center from 2012-2020. Those undergoing second IRE or IRE for other diagnoses were excluded. Primary end points included patterns of adjuvant and palliative therapy, overall survival (OS), recurrence free survival (RFS) and Clavien-Dindo complications. Therapy-free interval was defined as time from last neoadjuvant chemotherapy or radiation to the initiation of adjuvant or palliative therapy for recurrence. OS and RFS were evaluated by Kaplan Meier analysis and compared via log-rank test. Potential predictive factors were evaluated by Cox proportional hazard regression. Results: Of 110 patients, 46 underwent in situ IRE and 64 for margin extension. Eight (7.27%) were treated for recurrent pancreatic adenocarcinoma. Patients were similar in baseline characteristics, tumor location, and receipt of neoadjuvant chemotherapy. Median overall tumor size of 3.4 (2.8-4.0) on preoperative imaging was not different between IRE approach (p= 0.2810), Median OS from diagnosis (28.18 months, IQR 15.94-51.91) was similar for in situ vs. resection with margin extension (30.03 vs. 24.59 months, p=0.3298). There was no difference in local/distant RFS (respectively 7.26 vs. 10.59 months, p=0.7543). Both groups were similar with regard to Grades 3-5 90-day complications (28.3% vs. 25.0%, p=0.7018). Univariate Cox regression found no individual predictors of survival or recurrence to be significant. Adjuvant chemotherapy was given to 25.53% of patients who survived beyond 90 days. Thirty-two (34.04%) were not initially treated with adjuvant therapy, but later received treatment for recurrence. This group benefitted from a median therapy-free interval of 12.08 months (9.14-27.59) from last neoadjuvant chemotherapy or radiation, while maintaining similar overall survival (21.09 months vs. 20.96 months for planned adjuvant therapy, p=0.454). Conclusion: Many patients in this series would not have been candidates for traditional surgical resection. Compared to historical controls and studies of systemic therapy alone, this study demonstrates the favorable survival outcomes of IRE. By demonstrating a median one year treatment-free interval from neoadjuvant chemotherapy or radiation, this study highlights the potential for IRE to improve quality of life by limiting the inconveniences and toxicities of systemic therapy and raises questions about the role of adjuvant therapy after maximal neoadjuvant therapy for these selected patients.

Factors Affecting Total Operating Time in Patients Undergoing Mastectomy With and Without Reconstruction.

Operating room (OR) time varies significantly in patients undergoing mastectomy. We sought to determine factors influencing OR time such that more accurate predictions could be made. Records of patients undergoing mastectomy at our institution between January 2010 and June 2018 were reviewed. Operating Room time was defined as time from incision to dressing. Nonparametric analyses were performed to determine factors associated with OR time. A predictive model using linear regression was created on a training set and evaluated in a separate testing set. Our cohort included 1008 female patients who underwent either unilateral or bilateral mastectomy (BM), with or without reconstruction, and with or without concomitant axillary lymph node staging at our institution. The median OR time was 4.67hours (range; .70-16.35hours). To create a predictive model, we divided our cohort into a training set of 504 patients and a testing set of 504 patients. Across the training set, body mass index (BMI), BM, nonconventional mastectomies, intraoperative frozen sections, receipt of neoadjuvant chemotherapy, and reconstruction were associated with longer OR times on linear regression. A model generated from these findings on the training set was run on the testing set (Pearson correlation = .743 for predicted vs. actual OR times, P < .001). A number of preoperative factors such as BMI, unilateral vs. BM, type of mastectomy and reconstruction, use of intraoperative frozen sections, and receipt of neoadjuvant chemotherapy can influence OR times. Accurate predictions can be made using a simple model incorporating these factors.

Association of Neoadjuvant Chemotherapy With Overall Survival in Women With Metastatic Endometrial Cancer

Although primary debulking surgery (PDS) is often considered the criterion standard for treatment of stage IV endometrial cancer, PDS is associated with significant morbidity and poor survival. Neoadjuvant chemotherapy (NACT) has been proposed as an alternative treatment strategy. To determine the use of and outcomes associated with NACT for women with stage IV endometrial cancer. This cohort study used the National Cancer Database to identify women with stage IV endometrial cancer treated from January 1, 2010, to December 31, 2015. The cohort was limited to women aged 70 years or younger with minimal comorbidity (comorbidity score = 0). Women were stratified based on receipt of NACT or PDS. A propensity score analysis with inverse probability weighting was performed to balance the clinical characteristics of the groups. Survival was examined using flexible parametric Royston-Parmer models to account for time-varying hazards associated with use of NACT. An intention-to-treat (ITT) analysis was performed, as was a per-protocol (PP) analysis that included only women who received treatment with both chemotherapy and surgery (in either sequence). Data were analyzed from March 15, 2018, to July 20, 2018. Use of NACT and overall survival. Of a total of 4890 women (median age, 60 years [interquartile range, 54-65 years]) with stage IV endometrial cancer, NACT was used in 952 women (19.5%). Use of NACT increased from 106 of 661 women (16.0%; 95% CI, 13.2%-18.8%) in 2010 to 224 of 938 women (23.9%; 95% CI, 21.2%-26.6%) in 2015 (P < .001). In a multivariate model, more recent year of diagnosis (risk ratio [RR], 1.42; 95% CI, 1.21-1.79 for 2015 vs 2010), stage IVB disease (RR, 1.31; 95% CI, 1.03-1.67 for stage IVB vs IVA), and serous histology (RR, 1.38; 95% CI, 1.13-1.69 for serous vs endometrioid histology) were associated with use of NACT. In a propensity score-balanced cohort, use of NACT displayed a time-varying association with survival. In the ITT analysis, use of NACT was associated with decreased mortality for the first 3 months after diagnosis (hazard ratio [HR] at 2 months, 0.81; 95% CI, 0.66-0.99). After 4 months, the survival curves crossed, and receipt of NACT was associated with increased mortality (HR at 6 months, 1.23; 95% CI, 1.09-1.39). In the PP analysis, use of NACT was associated with decreased mortality for the first 8 months after diagnosis (HR at 6 months, 0.79; 95% CI, 0.63-0.98). After 9 months, the survival curves crossed, and receipt of NACT was associated with increased mortality (HR at 12 months, 1.22; 95% CI, 1.04-1.43). The results of this cohort study suggest that women treated with PDS are at increased risk of early death but have a more favorable long-term prognosis. In contrast, results suggest that women treated with NACT, particularly if they ultimately undergo surgery, may have superior survival in the short term. Based on these findings, NACT may be appropriate for select patients with advanced uterine serous carcinoma.

Determinants of adequate lymphnode dissection following neoadjuvant chemotherapy in patients with urothelial muscle-invasive bladder cancer: results from the National Cancer Database.

Recent literature has separately identified multiple determinants of the use of neoadjuvant chemotherapy (NAC) and adherence to pelvic lymphnode dissection (PLND) guidelines in the management of non-metastatic bladder cancer. However, such NAC/PLND analyses tend not to account for the other modality, despite the fact that NAC may impact the extent of dissectible lymph nodes. We aimed to determine the predictors of adequate PLND in patients with non-metastatic urothelial muscle-invasive bladder cancer (MIBC) undergoing radical cystectomy (RC) following receipt of NAC. We queried the National Cancer Database to identify patients from 2006-2015 with cT2-cT4a/N0M0 urothelial MIBC who underwent RC and were pre-treated with NAC. Multivariate logistic regression analysis was used to identify independent predictors of undergoing an adequate PLND (defined as > 8 nodes). A total of 1518 patients met the criteria for inclusion (74.4% underwent adequate PLND). Adequate PLND was associated with treatment at an academic research facility (OR 2.762 [95% CI 2.119-3.599], p < 0.001). The likelihood of adequate PLND was significantly decreased in patients of older age (0.607 [0.441-0.835], p = 0.002 for age 70-79years; 0.459 [0.245-0.860], p = 0.015 for age ≥ 80years), a Charlson-Deyo score of 1 (0.722 [0.537-0.971], p = 0.031), and those who were uninsured (0.530 [0.292-0.964], p = 0.038). Established predictors of PLND may not necessarily be generalizable to all patients undergoing treatment for bladder cancer. The interplay between PLND and NAC merits further study, particularly in view of recent literature calling into question the survival benefit of PLND in patients pre-treated with NAC.

Does multicenter care impact the outcomes of surgical patients with gastrointestinal malignancies requiring complex multimodality therapy?

Regionalization of oncologic care has increased, but less is known whether patient outcomes are influenced by receipt of multimodality care through multicenter care (MCC) or single-center care (SCC). Patients from 2004 to 2015 National Cancer Data Base diagnosed with stage II-III esophageal (EA), stage II-III pancreatic (PA), and stage II-IV rectal (RA) adenocarcinoma who underwent resection at a high volume center (HVC) and required radiation and/or chemotherapy were included. MCC (care at 2+ facilities) and SCC patients were propensity-score matched 1:2 and Cox proportional hazards regression used to analyze survival. On multivariable regression analysis, MCC in RA patients (N = 325/2097, 15.5%) was more associated with residing ≥40 miles from the HVC (odds ratio [OR] = 2.37; P = .044) and receipt of neoadjuvant chemotherapy (1.42, P = .040). In PA patients (N = 75/380, 19.7%), residing ≥40 miles from the HVC (OR = 3.22; P = .001), and in EA patients (N = 88/534, 16.5%), younger patients (<50 years: OR = 2.96; P = .011) were associated with MCC. Following propensity score matching, EA (N = 147), PA (N = 133), and RA (N = 661) patients had no difference in 1-year and 3-year overall survival when comparing MCC to SCC. The use of MCC appears safe without a difference in survival and may offer significant advantages in convenience to patients as they undergo their complex oncologic care.

Role of Neoadjuvant Chemotherapy in Squamous Variant Histology in Urothelial Bladder Cancer: Does Presence and Percentage Matter?

The purpose of this study was to evaluate the effect of neoadjuvant chemotherapy (NACT) on squamous variant (SV) bladder cancer by investigating patients presenting with SV histology at the time of transurethral resection (TUR), stratified by their receipt of NACT. The records of 71 patients with muscle-invasive bladder cancer and SV in the TUR specimen who underwent cystectomy between 2008 and 2018 were reviewed. Our primary outcome was pathologic response at time of cystectomy. Secondary outcomes included recurrence-free survival and overall survival stratified by receipt of NACT. A subgroup analysis was then conducted on the patients with defined SV% on TUR stratified by % involvement (< 50% SV vs.≥ 50% SV). The median age of the NACT and no-NACT groups was 60.2 and 70 years, respectively (P= .003). The complete response rate at cystectomy was 60% versus 13.7% for the NACT and no-NACT groups, respectively (P< .001). The non-organ-confined disease rate at time of radical cystectomy was 35% for the NACT group and 68.6% for the no-NACT group (P= .01). The NACT group had fewer recurrences than the no-NACT group (10% vs 47.1%; P= .003). In the subgroup analysis, the lower rate of non-organ-confined disease persisted for the patients who underwent NACT at the lower SV percentage but failed to remain significant at greater percentage involvement. This was also true for overall survival. The effect of NACT in variant histology bladder cancer is variable. In patients with SV, these results favor the recommendation in favor of NACT administration, particularly when the primary tumor has< 50% involvement by the variant histology.

Canadian experience of neoadjuvant chemotherapy on bladder recurrences in patients managed with trimodal therapy for muscle-invasive bladder cancer.

Bladder preservation with trimodal therapy (TMT) has emerged as a feasible alternative to radical cystectomy in patients with muscle-invasive bladder cancer. Neoadjuvant chemotherapy (NAC) was proven to cause pathological downstaging. For this reason, we evaluated whether receipt of NAC decreases local bladder recurrences in TMT patients. We retrospectively analyzed our TMT database for all patients treated between 2003 and 2017. Patients were treated with maximal transurethral resection of bladder tumor (TURBT) followed by chemotherapy/radiotherapy with or without NAC. Baseline demographic and tumor characteristics were recorded. Rates of local and systemic recurrence were analyzed per receipt of NAC. Overall recurrence-free survival (RFS) and bladder (b)RFS were analyzed using the Kaplan-Meier method and Cox proportional hazards modelling. Median age and followup periods were 72 years and 3.6 years, respectively. Fifty-four patients had NAC and concurrent chemoradiation (NAC-TMT) vs. 70 patients who had concurrent chemoradiation only (TMT). Carcinoma in situ (CIS) was present in 31% of the patients in NAC-TMT group compared to 24% in TMT group (p=0.40). After treatment, 24 (44%) and 31 (44%) patients in NAC-TMT and TMT groups, respectively, had bladder tumor recurrence. Overall RFS at three years was 46% and 50% in NAC-TMT and TMT groups, respectively (p=0.70). BRFS at three years was 55% and 69% in NAC-TMT and TMT groups, respectively (p=0.27). Multivariable analyses found that the presence of concomitant CIS (hazard ratio [HR] 2.13; 95% confidence interval CI 1.06-4.27; p=0.0036) was the primary factor associated with local bladder recurrence. Receipt of NAC does not obviate the risk of bladder recurrence post-TMT. Patients with CIS should be monitored especially closely for local recurrence.

The association between functional impairment pre- and post-cystectomy with neoadjuvant chemotherapy use in patients with muscle-invasive bladder cancer.

e17008 Background: Standard of care treatment for muscle-invasive bladder cancer (MIBC) includes neoadjuvant chemotherapy (NAC) followed by radical cystectomy (RC), which can be associated with major toxicity. It is unknown whether patients who receive NAC have differences in functional impairment prior to RC, degree of functional decline post-RC, or time to return to baseline functional status post-RC compared to patients who do not receive NAC. Methods: A total of 80 patients were included in this study. Patients completed an initial geriatric assessment (GA) post-NAC but prior to RC, which was repeated at 30, 90 days, and 1 year post-cystectomy. Patients were classified as impaired or not impaired on each GA domain based on previously established cut points. Percentage impairment was calculated as the number of domains impaired out of the total number of domain assessments completed for each patient at each time point. Results: Median age was 68 for patients who received NAC (66% received gemcitabine/cisplatin) and 72 for patients who did not (p = 0.06), with elevated creatinine as the most common reason for not receiving NAC (57%). Overall, 74% of patients were impaired on at least 1 GA domain pre-surgery (NAC 75%; no NAC 71%) and 86% at 30 days post-RC (NAC 86%; no NAC 87%). Groups did not differ significantly in percentage of patients impaired on each GA domain or median percentage impairment at any time point. For both groups, median percentage impairment increased significantly at 30 days post-RC compared to pre-RC (NAC: 36% vs. 15%, p &lt; 0.001; No NAC: 32% vs. 15%, p = 0.002), followed by a decrease in percentage impairment at 90 days post-RC compared to 30 days post-RC (NAC: 14% vs. 36%, p &lt; 0.001; No NAC: 16% vs. 32%, p = 0.15). There was no difference in impairment at 90 days post-RC compared to pre-RC (NAC: 14% vs. 15%, p = 0.41; No NAC: 16% vs. 15%, p = 0.31). Conclusions: Patients with MIBC frequently have functional impairments at baseline, and their degree of impairment worsens in the short term post-RC. However, patients return to their baseline function by 3 months post-RC. Receipt of NAC was not associated with increased levels of functional impairment at any time point or a delayed return to baseline.

Impact of Neoadjuvant Systemic Therapy on Pancreatic Fistula Rates Following Pancreatectomy: a Population-Based Propensity-Matched Analysis

IntroductionPostoperative pancreatic fistula (POPF) drives morbidity and mortality following pancreatectomy. Use of neoadjuvant chemotherapy (NAC) has recently increased in the treatment of potentially resectable pancreatic ductal adenocarcinoma (PDAC). This study examined the effect of NAC on POPF rates and postoperative outcomes in PDAC. MethodsThe American College of Surgeons-National Surgical Quality Improvement Program (NSQIP) Targeted Pancreatectomy dataset was queried to identify PDAC patients who underwent curative-intent pancreatectomies. Propensity score matching was used to stratify patients by receipt of NAC. Postoperative outcomes were compared and logistic regression applied to identify POPF predictors. ResultsSix thousand eight hundred sixty-three patients met the inclusion criteria; of those, 1908 (27.8%) received NAC and 4955 (72.2%) did not (NNAC). Two thousand sixty-two patients were matched 1:1 from each group. NAC patients had significantly lower POPF rates (9.0% vs. 14.5%; P < 0.001); the majority were categorized as grade A (5.1% vs. 9.5%). Overall 30-day morbidity was lower with NAC (40.4% vs. 49.5%; P < 0.001). Specifically, pneumonia (2.3% vs. 4.1%), organ space infections (7.9% vs. 13.2%), sepsis (5.2% vs. 8.0%), and delayed gastric emptying (10.1% vs. 14.8%) occurred less frequently in the NAC group. Postoperative mortality and unplanned reoperations were similar. On multivariate analysis, receipt of NAC was an independent predictor of decreased POPF rates (HR, 0.73 [0.56–0.94]; P = 0.016). Other factors included gland texture, duct size, male gender, and lower BMI. ConclusionsIn this propensity-matched, population-based cohort study of PDAC patients, NAC was associated with lower POPF rates and overall major complications. Those findings suggest a modest protective effect of NAC from POPF.

P7 Are women commencing Neoadjuvant Chemotherapy (NAC) for Primary Breast Cancer (PBC) more likely to experience distress compared to women undergoing surgical intervention or Adjuvant Chemotherapy (AC)?

Background and purpose In the wake of the burgeoning use of NAC as a first-line treatment for PBC, it is imperative for the multidisciplinary team to assess the manifestations of distress among this group of women to enable initiation of timely supports aimed at easing the burden of distress (Lo-Fo-Wong et al. 2016). This study aimed to compare the prevalence and aetiological contributors of distress experienced by women across three treatment modality groups. Methods This cross-sectional pilot study involved retrospective review of data extracted from validated Distress Screening Tools (DSTs) completed by 58 women upon commencement of either NAC, undergoing surgery or AC for PBC. The prevalence of distress according the distress thermometer and aetiological contributors of distress as per the 34-point problem checklist incorporating practical, family, emotional, spiritual/religious and physical problems experienced by women commencing NAC were compared to women undergoing surgical intervention or commencing AC. Results Elevated distress was experienced by 80% (n=8) of women upon receipt of NAC, compared to 67% (n=18) of women in the surgical group and 71% (n=15) of women commencing AC. Moreover, despite baring the youngest mean age of the three modality groups, yet to endure surgical recovery or potential adversities associated with chemotherapy treatment, women who underwent NAC also identified a greater number of aetiological contributors of distress. Women commencing NAC were more likely to identify emotions such as fear, nervousness and sadness, possibly generated from uneasiness associated with the back-to-front treatment regimen, questioning treatment efficacy, and being of younger age with associated additional demands imparted by family and lifestyle commitments (Beaver et al. 2016). Conclusion These results suggest the need for timely distress screening among this cohort, alerting the potential for referrals for supportive care aimed at optimising emotional well-being and easing the burden of distress. Beaver, K., Williamson, S. and Briggs, J. 2016. Exploring patient experiences of neoadjuvant chemotherapy for breast cancer. European Journal of Oncology Nursing. 20:77-86. doi:10.1016.j.ejon.2015.06.001Lo-Fo-Wong, D.N.N., de Haes, H.C.J.M., Aaronson, N.K., van Abbema, D.L., den Boer, M.D., van Hezewijk, M., Immink, M., Kaptein, A., Menke-Pluijmers, M.B.E., Reyners, A.K.L., Russell N.S., Schreik, M., Sijtsema, S., van Tienhoven G and Sprangers, M.A.G. 2016. Predictors of enduring clinical distress in women with breast cancer. Breast Cancer Research and Treatment. 158(3):563-572. https://doi.org/10.1007/s10549-016- 3896-7

Increasing use of positron emission tomography among medicare beneficiaries undergoing radical cystectomy.

To examine factors associated with PET scan use in the pre-operative evaluation of patients diagnosed with bladder cancer. Using SEER-Medicare data, we identified bladder cancer patients who underwent radical cystectomy from 2006 to 2011 (n=4,138). The primary outcome was PET scan use within 6months before surgery. To examine predictors of PET scan use, we fit a mixed logit model with health service area as a random effect to account for patients nested within health service areas. We also calculated the adjusted probability of use over time and examined variation among the highest volume surgeons. Among the 4,138 patients, 406 (10%) received a pre-operative PET scan. The adjusted probability of a patient undergoing a PET scan increased from 0.04 in 2004 to 0.10 in 2011 (p<.001). Among the 78 highest volume surgeons, there was significant variation in PET scan use (p<.001). Patients with non-urothelial histology, measurement of alkaline phosphatase levels, and receipt of neoadjuvant chemotherapy were more likely to receive PET scan (all p<.05). Use of PET prior to radical cystectomy doubled over a 5-year period, suggesting its increased use in patients with muscle-invasive bladder cancer, particularly those with high-risk disease. Whether its use is warranted and improves patient outcomes is not clear and requires further studies.

The Role of Neoadjuvant Chemotherapy in Patients With Resectable Malignant Pleural Mesothelioma-An Institutional and National Analysis.

There is no standard of care with respect to the use of neoadjuvant chemotherapy (NAC) in resectable malignant pleural mesothelioma (MPM). We performed an intention-to-treat analysis with data from a single institution and the National Cancer Database (NCDB) to identify whether the use of NAC impacts survival in resectable MPM. Patients with MPM who had surgery with curative intent at Duke University from 1995 to 2017 were selected, and the 2004-2015 NCDB was used to identify MPM patients with clinical stage I-IIIB who underwent definitive surgery. For both cohorts, patients were stratified by receipt of NAC. Primary outcomes were overall survival and postresection survival (RS), which were estimated using Kaplan-Meier and multivariable Cox proportional hazards models. A total of 257 patients met inclusion criteria in the Duke cohort. Compared with immediate resection (IR), NAC was associated with similar overall survival but an increased risk for postresection mortality in both unmatched (adjusted hazard ratio [HR] = 1.85, 95% confidence interval [CI] = 1.21 to 2.83) and propensity-matched (HR = 1.62, 95% CI = 1.03 to 2.55) cohorts. A total of 1949 NCDB patients were included: 1597 (81.9%) IR and 352 (18.1%) NAC. RS was worse for patients undergoing NAC in both unmatched (HR = 1.85, 95% CI = 1.21 to 2.83) and propensity-matched (HR = 1.29, 95% CI = 1.06 to 1.57) analyses compared with patients receiving IR. In this intention-to-treat study, NAC was associated with worse RS compared with IR in patients with MPM. The risks and benefits of induction therapy should be weighed before offering it to patients with resectable MPM.

Urinary Diversion Disparity Following Radical Cystectomy for Bladder Cancer in the Hispanic Population

ObjectiveTo determine if disparities in quality of surgical care exist between Hispanics and non-Hispanics undergoing radical cystectomy for bladder cancer. Materials and MethodsAn observational cohort study was conducted retrospectively on patients who underwent radical cystectomy for urothelial carcinoma of the bladder at our institution between January 2005 and July 2018. Data was collected on demographic, clinical, and pathological characteristics of patients, including self-reported ethnicity. Univariable and multivariable logistic or linear regression analyses were used to evaluate the association of ethnicity with receipt of neoadjuvant chemotherapy, utilization of laparoscopic surgery, number of lymph nodes removed, and continent urinary diversion. ResultsWe identified 507 patients in our database out of which, 136 (27%) were Hispanic and 371 (73%) were non-Hispanic. Compared to non-Hispanics, Hispanics had a higher body mass index (26.9 kg/m2 vs 28.2 kg/m2, P = .006) and lived further away from site of surgery (34 vs 96 miles, P = .02). No significant differences were observed in receipt of neoadjuvant chemotherapy, laparoscopic surgery, or number of lymph nodes removed during cystectomy between ethnicity groups. However, Hispanics were less likely than non-Hispanics to receive a continent urinary diversion on multivariable analysis (odds ratio 0.30, 95% confidence interval 0.10 - 0.92, P = .03). ConclusionDisparity exists in the delivery of continent urinary diversions for Hispanic patients undergoing radical cystectomy for bladder cancer. Further investigation is needed to determine the potential causes for this disparity in care delivered.

Trends in Extended-Duration Venous Thromboembolism Prophylaxis Following Radical Cystectomy

To evaluate temporal trends in prescriptions for extended-duration pharmacologic prophylaxis (EDPP) intended to prevent venous thromboembolism following radical cystectomy (RC). We used OptumLabs Data Warehouse, a national administrative claims database, to identify patients undergoing RC for bladder cancer from 2012 to 2017. Rates of outpatient prescriptions for EDPP following RC were assessed, and rate over time was evaluated using the Cochran-Armitage test for trend. Multivariable logistic regression was used to examine associations between clinical and practice-level characteristics with EDPP prescriptions. A total of 2054 patients were identified, including 386 (19%) who received an EDPP prescription. The rate of EDPP prescriptions increased significantly over the study period, from 9% of cases in 2012 to 26% of cases in 2017 (P <.001). On multivariable logistic regression, age <65 (OR 1.79, 95% CI 1.39-2.33; P <.001), receipt of neoadjuvant chemotherapy (OR 1.33, 95% CI 1.04-1.71; P = .02), more recent procedure year (OR 4.11, 95% CI 2.35-7.18; P <.001), treatment in a public as compared to a for-profit hospital (OR 3.38, 95% CI 1.31-8.74; P = .01), and treatment at a hospital with residency training (OR 4.45, 95% CI 1.26-15.7; P = .02) or a surgical robot (OR 3.44, 95% CI 1.31-9.08; P = .01) were significantly associated with increased odds of receiving EDPP. EDPP following RC has increased over time, but is still provided for only a minority of patients. These data may be useful for guiding quality improvement efforts given recent literature supporting the use of EDPP.

Screening logs from a pilot randomized controlled trial of radical cystectomy versus chemoradiation therapy for muscle-invasive bladder cancer

Introduction and objectivesThere is growing interest in a bladder preservation approach using chemoradiation therapy with transurethral resection of bladder tumor (TURBT), i.e., combined modality treatment (CMT), for muscle-invasive bladder cancer (MIBC). We have initiated a pilot study to determine feasibility of conducting a larger-scale clinical trial comparing CMT to radical cystectomy (RC) in patients with MIBC. Here we present the screening logs from the recruitment phase of this trial. MethodsPatients who were diagnosed to have MIBC after TURBT between April 2016 and August 2017 and considered to be candidates for surgery were enrolled in this prospective, single center, randomized controlled pilot feasibility trial and scheduled to undergo RC (with neoadjuvant chemotherapy if appropriate) or CMT. ResultsOf 62 patients screened during the recruitment phase, only 5 were found to be suitable candidates for either treatment modality hence eligible for randomization. The reasons for exclusion were as follows: multifocal disease (n = 24, 40%), variant histology (n = 15, 25%), previous pelvic radiation (n = 6, 10%), severe lower urinary tract symptoms (n = 5, 8.3%), unwillingness to be enrolled (n = 8, 13.3%), and receipt of neoadjuvant chemotherapy (n = 2, 3.3%). One of the 5 eligible patients was randomized to CMT but was subsequently switched to RC because of a high tumor burden, 1 was randomized to RC, 2 were randomized to CMT but subsequently underwent TURBT and were considered ineligible because of extensive bladder disease, and 1 elected to undergo RC. ConclusionsWe identified many patients with MIBC over a period of 16 months. However, the number of patients eligible to receive chemotherapy and in whom cystectomy and radiation therapy were both valid options was not as high as previously reported in retrospective CMT series. Many patients were excluded after TURBT. Our preliminary data indicate that only a very small subset of patients with MIBC are ideal candidates for CMT. Further research is required to identify patients who are suitable for CMT.

The impact of underinsurance on bladder cancer diagnosis, survival, and care delivery for individuals under the age of 65years.

Health insurance is a key mediator of health care disparities. Outcomes in bladder cancer, one of the costliest diseases to treat, may be especially sensitive to a patient's insurance status. The Surveillance, Epidemiology, and End Results registry and the National Cancer Data Base were used to identify individuals younger than 65years who were diagnosed with bladder cancer from 2007 to 2014. The associations between the insurance status (privately insured, insured by Medicaid, or uninsured) and the following outcomes were evaluated: diagnosis with advanced disease, cancer-specific survival, delay in treatment longer than 90days, treatment in a high-volume hospital, and receipt of neoadjuvant chemotherapy (NAC). Compared with those with private insurance, uninsured and Medicaid-insured individuals were nearly twice as likely to receive a diagnosis of muscle-invasive bladder cancer (odds ratio [OR] for uninsured individuals, 1.90; 95% confidence interval [CI], 1.70-2.12; OR for Medicaid-insured individuals, 2.03; 95% CI, 1.87-2.20). They were also more likely to die of bladder cancer (adjusted hazard ratio [AHR] for uninsured individuals, 1.49; 95% CI, 1.31-1.71; AHR for Medicaid-insured individuals, 1.61; 95% CI, 1.46-1.79). Delays in treatment longer than 90days were more likely for uninsured (OR, 1.36; 95% CI, 1.12-1.65) and Medicaid-insured individuals (OR, 1.22; 95% CI, 1.03-1.44) in comparison with the privately insured. Uninsured patients had lower odds of treatment at a high-volume facility, and Medicaid-insured patients had lower odds of receiving NAC (P<.001 for both). Compared with privately insured individuals, uninsured and Medicaid-insured individuals experience worse prognoses and poorer care quality. Expanding high-quality insurance coverage to marginalized populations may help to reduce the burden of this disease.