Impact Of Neoadjuvant Chemotherapy Research Articles

Accuracy of CT Scan in Predicting the Surgical PCI in Patients Undergoing Cytoreductive Surgery with/without HIPEC-a Prospective Single Institution Study.

Our aim was tostudy the accuracy of CT scan in predicting the peritoneal cancer index (PCI) and the impact of neoadjuvant chemotherapy (NACT), abdominal region, disease volume, and primary tumor site on it. This was a prospective single-center study that included patients undergoing cytoreductive surgery ± HIPEC. The CT-PCI was calculated and compared to the surgical PCI. The accuracy of CT-PCI in predicting the surgical PCI and the difference between the two was evaluated. From January 2018 to August 2018, 50 patients were included. The median CT PCI was 6 (range 0-35) and median surgical PCI was 17 (range 2-35). CT-PCI was more than the surgical PCI in 12 (24%), less in 23 (46%), and same in 15 (30%) with an accuracy of 30%. The highest accuracy was in region 10 and lowest in region 3. It was 15% in patients with ovarian cancer, 30% in PMP, 21% in patients receiving NACT, 35% in high-volume disease, and 42.1% in low volume disease. The CT and surgical PCI varied significantly in patients with ovarian cancer (p < 0.001), following NACT (p = 0.01) and those with moderate volume disease (p < 0.001). CT has a low accuracy in predicting the surgical PCI in both high and low volume disease. The CT-PCI can differ significantly from the surgical PCI in patients with ovarian cancer and in patients who have received NACT for peritoneal disease. The impact of NACT on accuracy of CT-PCI in non-ovarian peritoneal metastases should be evaluated further.

Impact of Neoadjuvant Chemotherapy on the Postoperative Outcomes of Patients Undergoing Liver Resection for Colorectal Liver Metastases: A Population-Based Propensity-Matched Analysis

The role of neoadjuvant chemotherapy in the management of colorectal liver metastases remains controversial. We sought to investigate whether neoadjuvant systemic chemotherapy contributes to clinically significant increases in postoperative morbidity and mortality using a population-based cohort. The American College of Surgeons NSQIP Targeted Hepatectomy Participant Use Files were queried from 2014 to 2016 to identify patients with colorectal liver metastases who underwent liver resection. Patients were stratified by receipt of neoadjuvant chemotherapy using propensity score matching. Univariate and multivariable analyses were used to characterize the effect of neoadjuvant chemotherapy on perioperative morbidity and mortality. After propensity score matching, 1,416 (50%) patients received neoadjuvant chemotherapy before hepatectomy and 1,416 (50%) underwent liver resection without neoadjuvant chemotherapy. There were no differences in age (60 vs 61 years), maximum tumor size (≤5 cm: 79% vs 80%, >5 cm: 21% vs 20%), resection type (partial hepatectomy: 69% vs 70%), simultaneous colectomy (9% vs 9%), or use of preoperative portal vein embolization (5% vs 5%) in those undergoing neoadjuvant chemotherapy compared with those who did not (all, p > 0.05). Overall 30-day postoperative morbidity (34% vs 33%), including rates of biliary fistula (6% vs 5%), post-hepatectomy liver failure (5% vs 5%), and mortality rates (0.8% vs 0.7%), were similar among patients who received neoadjuvant chemotherapy vs those who did not (all, p > 0.05). On multivariable analysis, receipt of neoadjuvant chemotherapy was not associated with increased morbidity (odds ratio 1.07; 95% CI 0.90 to 1.27; p= 0.43) or mortality (odds ratio 1.09; 95% CI 0.44 to 2.72; p= 0.85). In this propensity-matched population-based cohort study, the use of neoadjuvant systemic chemotherapy was not associated with higher rates of complications, biliary fistula, post-hepatectomy liver failure, or mortality among patients with colorectal liver metastases undergoing liver resection.

PT331 - Impact of neoadjuvant chemotherapy on bladder recurrences in patients managed with trimodal therapy (TMT) for muscle-invasive bladder cancer

PT331 - Impact of neoadjuvant chemotherapy on bladder recurrences in patients managed with trimodal therapy (TMT) for muscle-invasive bladder cancer

Impact of neoadjuvant chemotherapy and stereotactic body radiation therapy (SBRT) on R0 resection rate for borderline resectable and locally advanced pancreas cancer.

370 Background: Management for borderline resectable pancreas cancer (BRPC) and locally advanced pancreas cancer (LAPC) is controversial. Multiagent chemotherapy (CT) followed by SBRT may allow for tumor downstaging and the ability to perform an R0 resection. Methods: We retrospectively evaluated BRPC and LAPC patients (pts) treated on our multidisciplinary treatment pathway. Pts underwent 2-3 months of CT. Pts without systemic progression received five fractions of SBRT, delivered every other day, to a dose of 30-33 Gy. After restaging, pts underwent surgery if resectable. Overall survival (OS), distant metastasis free survival (DMFS) and local progression free survival (LPFS) were estimated and compared by Kaplan-Meier and log-rank methods. Results: We identified 80 pts with BRPC (65) or LAPC (15) treated with neoadjuvant CT + SBRT between 2011-2017. Median follow up was 20 months. CT primarily included FOLFIRINOX (65%) and gemcitabine/nab-paclitaxel (30%). Of pts completing CT + SBRT, 67 (84%) went to surgery and 53 (79%) of those pts underwent definitive surgery including seven LAPC patients. The remaining 14 pts underwent palliative or exploratory surgery due to intraoperative metastases (43%) or vascular involvement (57%). Of pts undergoing definitive surgery, 51 had R0 resection (96%) and 5 (9%) had a complete pathologic response (PR) to CT + SBRT. The R0 resection rate of the cohort was 64%. OS was 24.5 months. Pts with a complete or marked (14%) PR had significantly better OS than those with a moderate (40%) PR (41.3 vs 30 months, p = 0.04) and pts unable to undergo definitive surgery (18.2 months, p &lt; 0.001). Zero of 11 pts who had a marked or complete PR had local progression, significant compared to those with moderate PR (p = 0.012). DMFS between these two groups was not statistically significantly different. Conclusions: Neoadjuvant CT + SBRT are associated with favorable PR rates and R0 resection rates. Marked or complete PR was associated with improved LPFS and OS compared to moderate PR and pts who did not undergo definitive surgery. DMFS was not significantly different between complete and marked PR compared to those with moderate PR.

Neoadjuvant Chemotherapy with Taxane and Platinum Followed by Radical Hysterectomy for Stage IB2-IIB Cervical Cancer: Impact of Histology Type on Survival.

The current study examined the histology-specific impact of neoadjuvant chemotherapy (NACT) with a taxane/platinum regimen on survival in women with locally-advanced cervical cancer who underwent radical hysterectomy. This nation-wide retrospective cohort study examined women with clinical stage IB2-IIB cervical cancer who received NACT prior to radical hysterectomy from 2004–2008 (n = 684). NACT type (taxane/platinum versus others) was correlated with survival based on histology: 511 squamous versus 173 non-squamous. Taxane/platinum chemotherapy use was more common in non-squamous compared to squamous tumors (53.8% versus 20.7%, P < 0.001). In both histology types, the taxane/platinum regimen was more frequently utilized over time (both, P < 0.01). Among squamous tumors, women who received taxane/platinum chemotherapy had survival comparable to those who received other regimens: 5-year rates for disease-free survival, 69.0% versus 70.1%, P = 0.98; and cause-specific survival, 80.0% versus 81.0%, P = 0.93. Similarly, in non-squamous tumors, disease-free survival (5-year rates: 60.4% versus 59.0%, P = 0.86) and cause-specific survival (74.7% versus 76.3%, P = 0.70) were similar. In conclusion, use of taxane/platinum regimens for NACT significantly increased during the study period. Irrespective of histology type, in women with clinical stage IB2-IIB cervical cancer who underwent NACT prior to radical hysterectomy, taxane/platinum regimens had a similar effect on survival compared to non-taxane/platinum regimens.

Expression of programmed cell death ligand 1 and immune checkpoint markers in residual tumors after neoadjuvant chemotherapy for advanced high-grade serous ovarian cancer

ObjectiveTo investigate the prognostic value of the expressions of programmed cell death ligand 1 (PD-L1) and immune checkpoint markers in residual tumors after neoadjuvant chemotherapy (NAC) for advanced high-grade serous ovarian cancer (HGSOC). MethodsWe collected pre- and post-NAC tumor samples from patients with advanced HGSOC between 2006 and 2017. Post-NAC tumor tissue samples were available for immunostaining from 131 patients. The expressions of PD-L1 and immune checkpoint markers were assessed by immunohistochemical staining and the status of tumor-infiltrating lymphocytes (TILs) was also evaluated. We examined whether there are significant associations between protein expression status and patient outcomes and whether significant changes in protein expression levels occurred in response to NAC. ResultsPD-L1 expression in the tumor cells was evaluated in 113 patients, 12 (10.6%) of whom had high PD-L1 expression (≥25%) in post-NAC tissues. However, these high levels were not associated with progression-free survival (PFS; P = 0.348) or overall survival (OS; P = 0.699). Similarly, high stromal TILs [≥50%; n = 16 (15.0%)] among the 107 patients evaluated did not show any significant impact on PFS (P = 0.250) or OS (P = 0.800). Moreover, an abundance of TILs (intraepithelial, CD8+, and Foxp3+) and the expression of immune checkpoint markers (PD-1, ICOS, and LAG-3) in residual tumors did not confer any significant survival benefit. The impact of NAC on PD-L1 expression and stromal TILs varied considerably among individual patients. ConclusionAlthough the expression of PD-L1 and immune checkpoint markers in residual tumors after NAC had no prognostic impact on survival in patients with HGSOC, post-NAC evaluation of these proteins in chemoresistant tumors may help select patients for immunotherapy trials.

Impact of Neoadjuvant Chemotherapy on Postoperative Complications: Analysis of the American Society of Breast Surgeons Nipple-Sparing Mastectomy Registry

Impact of Neoadjuvant Chemotherapy on Postoperative Complications: Analysis of the American Society of Breast Surgeons Nipple-Sparing Mastectomy Registry

Impact of Neoadjuvant Chemotherapy on Pathologic Response in Patients With Upper Tract Urothelial Carcinoma Undergoing Extirpative Surgery.

Neoadjuvant chemotherapy (NAC) has been increasingly adopted in the management of high-grade upper tract urothelial carcinoma (UTUC), largely extrapolating from level I evidence in urothelial carcinoma of the bladder. Studies examining pathologic outcomes in patients with UTUC receiving NAC are mostly limited to retrospective, single-center studies with limited sample size, with results of a phase II trial recently presented. Hypothesizing that NAC is associated with improved pathologic response (PR), we compared pathologic outcomes in patients with high-grade UTUC who did and did not receive NAC before extirpative surgery. A total of 6174 patients with nonmetastatic, high-grade UTUC who underwent extirpative surgery from 2006 to 2014 were identified from the National Cancer Database. Patients were stratified by NAC status. PR was defined as pathologic stage less than clinical stage. Univariate and multivariable logistic regression analysis was employed to identify predictors of PR. Two hundred sixty (4.2%) patients received NAC. A higher incidence of PR was observed in patients receiving NAC (25.2% vs. 1.8%; P< .001), with complete PR observed in 6.1% of patients receiving NAC and 0.4% of patients undergoing surgery alone. NAC (odds ratio [OR], 19.8; 95% confidence interval [CI], 11.8-33.5), nonwhite race (OR, 3.2; 95% CI, 1.7-6.3), and ureteral tumor location (OR, 1.6; 95% CI, 1.02-2.6) were independently associated with PR. Examining a large national cancer registry, we observed a higher incidence of PR in patients with UTUC receiving NAC, validating findings of prior studies. Our findings support consideration of NAC in high grade UTUC. Prospective trials will better define the impact of NAC on pathologic and survival outcomes.

Impact of Neoadjuvant Chemotherapy on the Administration of Concurrent Chemoradiation for Locally Advanced Nasopharyngeal Carcinoma

ObjectivesThe standard of care for locally advanced nasopharyngeal carcinoma (NPC) is concurrent cisplatin chemoradiotherapy. Neoadjuvant chemotherapy can be administered to downsize tumors before concurrent treatment to optimize radiation volumes. Our hypothesis was that the use of cisplatin in the neoadjuvant phase could limit the amount of cisplatin that patients could tolerate in the concurrent phase of treatment.MethodsThis is a retrospective analysis of Canadian NPC patients who received neoadjuvant chemotherapy with the intention to downsize locally advanced tumors prior to concurrent cisplatin plus radiation. Baseline demographic and treatment data were obtained from institutional databases and chart review; all data were analyzed with SPSS (SPSS Inc. Released 2005. SPSS for Windows, Version 14.0. Chicago: SPSS Inc.) Overall survival (OS), disease-specific survival (DSS), and local/regional relapse-free survival (LRRFS) were analyzed using Kaplan-Meier survival functions. Univariate and multivariate models were used to determine factors associated with the total dose of concurrent chemotherapy.ResultsForty-six patients were identified as receiving neoadjuvant chemotherapy before concurrent chemoradiotherapy. In the univariate and multivariate analyses of patients who received concurrent chemotherapy, receiving over 200 mg/m2 concurrent cisplatin with radiation was associated with a higher neoadjuvant dose of chemotherapy received. The median follow-up time was 2.6 years (range, 0.17 years to 10.6 years). At three years, the OS was 83%, DSS was 86%, and LRRFS was 74%.ConclusionsNPC patients have been treated with neoadjuvant chemotherapy at this center with favorable outcomes. Most patients could tolerate concurrent chemotherapy after radiotherapy. Receiving higher doses of concurrent chemotherapy was associated with also having higher doses of neoadjuvant cisplatin. This suggests that neoadjuvant cisplatin is not a limiting factor in the delivery of full-dose concurrent chemotherapy.

Impact of Neoadjuvant Chemotherapy on Breast Cancer Subtype: Does Subtype Change and, if so, How?

Breast cancer subtype, as determined by the expression of estrogen receptor (ER) and progesterone receptor (PR), together defined as hormone receptor (HR) status, and the HER2/neu receptor (HER2), is important in predicting prognosis and guiding therapy. Knowledge regarding how tumors evolve during treatment and whether subtype is influenced by neoadjuvant chemotherapy (nCT) is limited. The purpose of this study was to compare the HR and HER2 status between core needle biopsy and residual tumor after surgery of breast cancer patients treated with nCT and to evaluate the impact of status change on therapeutic management. After institutional review board approval, we performed a retrospective review of all patients with a diagnosis of breast cancer who received nCT and had their initial biopsy and post-nCT surgical specimens evaluated for tumor subtype between January 2009 and December 2014 at our institution. Immunohistochemistry (IHC) of ER, PR, HER2, and fluorescence in situ hybridization for HER2 expression, when indicated, was performed using identical technique and measured by a single pathologist who specializes in breast pathology. Pre- and post-nCT subtype was cross-tabulated to assess change. Standard diagnostic metrics were computed. Fifty-two patients with 54 cancers were identified to have their initial biopsy and post-nCT surgical specimens evaluated for tumor subtype in identical fashion. There was a complete pathologic response after nCT in 23 cancers (42.6%). Residual disease was noted in 31 cancers (57.4%). Five of these (16.1%) had a change in tumor subtype, of which four changes were based on IHC. HR status changed from positive to negative in two cases and from negative to positive in one case. HER2 status changed from positive to negative in one case and from negative to positive in one case. Subtype change led to treatment change in all five cases, with either the addition or discontinuation of adjuvant therapies. Patients with breast cancer may experience alterations in their tumor subtype after nCT. At our institution, this led to a change in adjuvant treatment in 100% of such patients. This implies that retesting receptor status of residual tumors after nCT should be routinely performed to tailor adjuvant therapy after nCT.

The impact of neoadjuvant chemotherapy on re-excision rates after breast-conserving surgery

Introduction: Neoadjuvant chemotherapy (NACT) is increasingly used in early operable breast cancer if the tumour phenotype is appropriate. There is conflicting evidence that NACT may reduce margin re-excision rates (RER) after breast-conserving surgery (BCS). The objective of this study was to test this hypothesis and explore the impact of NACT on RER in the setting of a tertiary cancer hospital.

Impact of neoadjuvant chemotherapy and pathological complete response on eligibility for breast-conserving surgery in patients with early breast cancer: A meta-analysis

PurposeWe conducted a meta-analysis of randomised trials evaluating pathological complete response (pCR) and surgical outcomes after neoadjuvant systemic therapy (NST) in patients with early breast cancer (EBC). Patients and methodsThe primary outcome was breast-conserving surgery (BCT) rate. Secondary outcomes were pCR rate and association to BCT. Meta-analyses were performed using random effects models that use inverse-variance weighting for each treatment arm based on evaluable patients. Point estimates are reported with 95% confidence interval (CI), and p < 0.05 was considered statistically significant. ResultsThirty-six studies were identified (N = 12,311 patients). We selected for the analysis 16 of 36 studies reporting both pCR and BCT for at least one treatment arm. Arms per study ranged from one to six; 42 independent units were available to evaluate the association between pCR and BCT. BCT rate ranged 5–76% across arms with an average BCT of 57% (95% CI 52–62%). Significant heterogeneity was observed among the trials (Cochrane Q = 787, p < 0.001, I2 = 97%). In the meta-regression model, BCT rates were not significantly associated with year of first patient-in (p = 0.89), grade (p = 0.93) and hormone-receptor status (p = 0.39). Clinical N-stage (p = 0.01) and human epidermal growth factor receptor (HER2) status (p = 0.03) were significantly associated with BCT. pCR rate ranged 3–60% across studies. The average pCR across all study arms was 24% (95% CI 19–29%). No association was observed between pCR rate in a study arm and the resulting BCT rate in a univariate model (p = 0.34) nor after adjusting for HER2 and clinical nodal status (p = 0.82). In the subset of 14 multi-arm studies, no significant association was seen between the differences in pCR and BCT between treatment arms (p = 0.27). ConclusionspCR does not increase BCT in patients receiving NST for EBC.

MP78-02 TRENDS IN NEOADJUVANT CHEMOTHERAPY USE AND ONCOLOGICAL OUTCOMES FOR MUSCLE-INVASIVE BLADDER CANCER IN JAPAN: A MULTICENTER STUDY

You have accessJournal of UrologyBladder Cancer: Invasive VI1 Apr 2018MP78-02 TRENDS IN NEOADJUVANT CHEMOTHERAPY USE AND ONCOLOGICAL OUTCOMES FOR MUSCLE-INVASIVE BLADDER CANCER IN JAPAN: A MULTICENTER STUDY Go Anan, Shingo Hatakeyama, Naoki Fujita, Hiromichi Iwamura, Toshikazu Tanaka, Hayato Yamamoto, Yuki Tobisawa, Tohru Yoneyama, Takahiro Yoneyama, Yasuhiro Hashimoto, Takuya Koie, Hiroyuki Ito, Kazuaki Yoshikawa, Toshiaki Kawaguchi, Makoto Sato, and Chikara Ohyama Go AnanGo Anan More articles by this author , Shingo HatakeyamaShingo Hatakeyama More articles by this author , Naoki FujitaNaoki Fujita More articles by this author , Hiromichi IwamuraHiromichi Iwamura More articles by this author , Toshikazu TanakaToshikazu Tanaka More articles by this author , Hayato YamamotoHayato Yamamoto More articles by this author , Yuki TobisawaYuki Tobisawa More articles by this author , Tohru YoneyamaTohru Yoneyama More articles by this author , Takahiro YoneyamaTakahiro Yoneyama More articles by this author , Yasuhiro HashimotoYasuhiro Hashimoto More articles by this author , Takuya KoieTakuya Koie More articles by this author , Hiroyuki ItoHiroyuki Ito More articles by this author , Kazuaki YoshikawaKazuaki Yoshikawa More articles by this author , Toshiaki KawaguchiToshiaki Kawaguchi More articles by this author , Makoto SatoMakoto Sato More articles by this author , and Chikara OhyamaChikara Ohyama More articles by this author View All Author Informationhttps://doi.org/10.1016/j.juro.2018.02.2550AboutPDF ToolsAdd to favoritesDownload CitationsTrack CitationsPermissionsReprints ShareFacebookTwitterLinked InEmail INTRODUCTION AND OBJECTIVES Despite benefits of neoadjuvant chemotherapy (NAC), the adoption of guideline recommendations for NAC use in patients with muscle-invasive bladder cancer (MIBC) has been slow. We aimed to evaluate temporal trends in NAC use and oncological outcomes in a representative cohort of patients with MIBC. METHODS We included 532 patients from 4 hospitals who underwent radical cystectomy (RC) for MIBC in 1996-2017. We retrospectively evaluated temporal changes in NAC use and progression-free and overall survival. Candidates for NAC were administered with either cisplatin- or carboplatin-based regimens. The impact of NAC on oncological outcomes was examined using multivariate Cox regression analysis with inverse probability of treatment weighting (IPTW) models. RESULTS Of 532 patients, 336 underwent NAC followed by RC (NAC group) and 196 underwent RC alone (Ctrl group). NAC use significantly increased from 10% (1996-2004) to 83% (2005-2016). The number of patients administered with cisplatin- and carboplatin-based regimens was 43 and 280, respectively. There were no significant differences between PFS and OS when comparing the cisplatin- and carboplatin-based therapies. The number of pT0 and pT3-4 patients was significantly higher and lower in the NAC group than the Ctrl group, respectively. Oncological outcomes in the NAC group were significantly improved compared to those in the Ctrl group in progression-free and overall survival. Multivariable analysis with IPTW models revealed that NAC significantly improved oncological outcomes in patients with MIBC. A nomogram for 5-year overall survival predicted 16% improvement in patients undergoing NAC. CONCLUSIONS NAC use for MIBC increased after 2005. Platinum-based NAC for MIBC potentially improves oncological outcomes. © 2018FiguresReferencesRelatedDetails Volume 199Issue 4SApril 2018Page: e1036-e1037 Advertisement Copyright & Permissions© 2018MetricsAuthor Information Go Anan More articles by this author Shingo Hatakeyama More articles by this author Naoki Fujita More articles by this author Hiromichi Iwamura More articles by this author Toshikazu Tanaka More articles by this author Hayato Yamamoto More articles by this author Yuki Tobisawa More articles by this author Tohru Yoneyama More articles by this author Takahiro Yoneyama More articles by this author Yasuhiro Hashimoto More articles by this author Takuya Koie More articles by this author Hiroyuki Ito More articles by this author Kazuaki Yoshikawa More articles by this author Toshiaki Kawaguchi More articles by this author Makoto Sato More articles by this author Chikara Ohyama More articles by this author Expand All Advertisement Advertisement PDF downloadLoading ...

Postoperative complications after resection of borderline resectable and locally advanced pancreatic cancer: The impact of neoadjuvant chemotherapy with conventional radiation or stereotactic body radiation therapy

BackgroundThe impact of neoadjuvant stereotactic body radiation therapy on postoperative complications for patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma remains unclear. Limited studies have compared neoadjuvant stereotactic body radiation therapy versus conventional chemoradiation therapy. A retrospective study was performed to determine if perioperative complications were different among patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma receiving neoadjuvant stereotactic body radiation therapy or chemoradiation therapy. MethodsPatients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma who underwent neoadjuvant chemotherapy with stereotactic body radiation therapy or chemoradiation therapy followed by pancreatectomy at the Johns Hopkins Hospital between 2008 and 2015 were included. Predictive factors for severe complications (Clavien grade ≥ III) were assessed by univariate and multivariate analyses. ResultsA total of 168 patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma underwent neoadjuvant chemotherapy and RT followed by pancreatectomy. Sixty-one (36%) patients underwent stereotactic body radiation therapy and 107 (64%) patients received chemoradiation therapy. Compared with the chemoradiation therapy cohort, the neoadjuvant stereotactic body radiation therapy cohort was more likely to have locally advanced pancreatic ductal adenocarcinoma (62% vs 43% P = .017) and require a vascular resection (54% vs 37%, P = .027). Multiagent chemotherapy was used more commonly in the stereotactic body radiation therapy cohort (97% vs 75%, P < .001). Postoperative complications (Clavien grade ≥ III 23% vs 28%, P = .471) were similar between stereotactic body radiation therapy and chemoradiation therapy cohort. No significant difference in postoperative bleeding or infection was noted in either group. ConclusionCompared with chemoradiation therapy, neoadjuvant stereotactic body radiation therapy appears to offer equivalent rates of perioperative complications in patients with borderline resectable or locally advanced pancreatic ductal adenocarcinoma despite a greater percentage of locally advanced disease and more complex operative treatment.

1030 - The impact of neoadjuvant chemotherapy on locally advanced upper tract urothelial carcinoma: A multicenter study

INTRODUCTION AND OBJECTIVE:The clinical impact of neoadjuvant chemotherapy (NAC) on oncological outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC) remains unclear. W...

The impact of neoadjuvant chemotherapy (NAC) on conditional survival (CS) among patients with muscle-invasive bladder cancer (MIBC).

520 Background: Achieving a pathologic complete response (pCR) with NAC for MIBC is associated with a favorable prognosis. Patients with pathologic residual disease (pRD) generally have poor outcomes. However, prognosis after radical cystectomy (RC) improves with ongoing survivorship. Whether the difference in prognosis of patients with pCR and pRD is sustained over time has not been explored. Methods: We queried the National Cancer Database for patients who received NAC and RC for clinically localized MIBC (cT2-T4aN0M0) between 2002-2010. We identified patients with pCR (&lt;/= pTis) and pRD. Using Kaplan-Meier analysis, we assessed CS up to 5 years given survivorship of 0-4 years using log-rank test with multiple comparison adjustment. Results: The cohort comprised 1,554 patients (pCR: 314, pRD: 1,240). The median follow up was 2.38 (0.04-9.60) and 2.76 (0.01-9.97) years for pCR and pRD, respectively. Patients with pCR had lower stage (cT2= 79% vs. 72%; cT3= 14% vs. 18%; cT4= 7% vs. 10%), more recent diagnosis (2010: 31% vs. 19%), and were more often treated at a high-volume center (&gt;15 RC/year: 61% vs. 49%). Patients with pCR had improved CS relative to those with pRD with survivorship up to 3 years, but the benefit associated with pCR becomes attenuated from 4 years post-RC (Table). Conclusions: MIBC patients with pRD after NAC have worse CS up to years 3 post-RC, but this difference diminishes after 4 years. These findings may inform patient counseling, surveillance intensity, and novel adjuvant approaches for patients with pRD, and are subject to confirmation with a forthcoming multivariable analysis. Probability of surviving to X years (95% CI). [Table: see text]

Impact of neoadjuvant chemotherapy on pathologic outcomes in patients with upper tract urothelial carcinoma undergoing extirpative surgery.

457 Background: Neoadjuvant chemotherapy (NAC) is infrequently administered to patients with upper tract urothelial carcinoma (UTUC) undergoing radical nephroureterectomy or segmental ureterectomy and its impact on pathologic outcomes unclear. We examine pathologic outcomes in patients with UTUC receiving NAC before extirpative surgery using a population-based cancer registry. Methods: Patients who underwent extirpative surgery for UTUC from 2006-2014 were identified from the National Cancer Database. Among patients with available clinicopathologic data, the incidence of pathologic down-staging, defined as a lesser pathologic compared to clinical stage, was compared between patients who did and did not receive NAC. A multivariable model was developed to identify predictors of pathologic down-staging. Results: 7,244 patients were identified with non-metastatic UTUC who underwent extirpative surgery in the study period. 260 patients (3.6%) received NAC, with the use of NAC increasing over time from 2.0% patients in 2006 to 7.1% of patients in 2014 (linear trend p &lt; 0.001). Clinical and pathologic staging data were available for 119 and 2904 patients who did and did not receive NAC, respectively. Thirty patients (25.2%) who received NAC experienced pathologic down-staging, compared to 52 patients (1.8%) who did not receive NAC (p &lt; 0.0001). On multivariable analysis, NAC was associated with a higher likelihood of pathologic down-staging (OR 10.2, 95% CI 5.4-19.3). Additional predictors of pathologic down-staging include a higher clinical T stage (p = 0.001) and African-American race (OR 2.7, 95% CI 1.1-6.6). Compared to renal pelvis UTUC, ureteral UTUC was associated with a similar likelihood of pathologic down-staging (OR 1.5, 95% CI 0.9-2.5). Conclusions: NAC is infrequently used among patients with UTUC undergoing extirpative surgery. A higher incidence of pathologic down-staging was observed among patients receiving NAC. These findings suggest clinical benefit of NAC with respect to pathologic outcomes in patients with UTUC and may help guide selection of patients for NAC prior to radical surgery until data from prospective studies becomes available.

Oncological outcomes of neoadjuvant chemotherapy in patients with locally advanced upper tract urothelial carcinoma: A multicenter study.

429 Background: The clinical impact of neoadjuvant chemotherapy (NAC) on oncological outcomes in patients with locally advanced upper tract urothelial carcinoma (UTUC) remains unclear. We investigated the oncological outcomes of platinum-based NAC for locally advanced UTUC. Methods: A total of 426 patients who underwent radical nephroureterectomy at five medical centers between January 1995 and April 2017 were examined retrospectively. Of the 426 patients, 234 were treated for a high-risk disease (stages cT3–4 or locally advanced [cN+] disease) with or without NAC. NAC regimens were selected based on eligibility of cisplatin. We retrospectively evaluated post-therapy pathological downstaging, lymphovascular invasion, and prognosis stratified by NAC use. Multivariate Cox regression analysis was performed for independent factors for prognosis. Results: Of 234 patients, 101 received NAC (NAC group) and 133 did not (Control [Ctrl] group). The regimens in the NAC group included gemcitabine and carboplatin (75%), and gemcitabine and cisplatin (21%). Pathological downstagings of the primary tumor and lymphovascular invasion were significantly improved in the NAC than in the Ctrl groups. NAC for locally advanced UTUC significantly prolonged recurrence-free and cancer-specific survival. Multivariate Cox regression analysis using an inverse probability of treatment weighted (IPTW) method showed that NAC was selected as an independent predictor for prolonged recurrence-free and cancer-specific survival. However, the influence of NAC on overall survival was not statistically significant. Conclusions: Platinum-based NAC for locally advanced UTUC potentially improves oncological outcomes. Further prospective studies are needed to clarify the clinical benefit of NAC for locally advanced UTUC.

Cisplatin-based neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC) in patients (pts) with impaired renal function.

446 Background: Cisplatin-based NAC followed by radical cystectomy is the standard of care in MIBC but many pts are cisplatin-unfit. Data in pts with low glomerular filtration rate (GFR) who receive cisplatin-based NAC is limited. Methods: A retrospective analysis of pts who received cisplatin-based NAC at Cleveland Clinic (2005-2016) was conducted. Pts with pre-NAC GFR &lt; 60 ml/min by either CG or MDRD formula (low GFR; N = 30) were compared to pts with GFR ≥60 (normal GFR; N = 94) in terms of NAC tolerability and outcomes including pathologic complete (pCR, pT0N0) and partial response (pPR, &lt; pT2N0). A secondary analysis compared 3 groups of pts: GFR &lt; 50ml/min (N = 10), GFR 50-59 ml/min (N = 20), and GFR ≥60 (N = 94). Results: Low GFR pts were older (median age 71 vs 65, p &lt; 0.001) and had higher rates of hydronephrosis (33% vs 15%, p = 0.03). ECOG PS, other demographic and TURBT features (stage, LVI, CIS) did not differ significantly. Low GFR pts were more likely to receive gemcitabine/cisplatin (83% vs 71%, p = 0.04) and get split-dose cisplatin (38% vs 16%, p = 0.02). Split-dose cisplatin use in low GFR pts did not impact NAC tolerability or outcomes. NAC cycles completed (median 3 per group) were comparable, and most low GFR pts (70%) completed intended NAC regimen. Low GFR pts were more likely to have early NAC discontinuation (30% vs 13%, p = 0.03) and NAC modification (delay, dose reduction, discontinuation) (66% vs 40%, p = 0.02). No differences were seen in cystectomy completion rate (93% per group), time to cystectomy, length of stay, surgical complications, and GFR change from baseline. Combined pCR/pPR was higher in normal GFR group (54% vs 25%, p = 0.01). Among pts with very low GFR ( &lt; 50 ml/min), 60% completed intended NAC regimen and 70% had NAC modification. Rates of pCR and pPR were low: 0% and 12%, respectively. Conclusions: Low GFR pts were older, had more NAC discontinuations/modifications and lower pCR/pPR rate, but most completed planned NAC cycles. Relative to normal GFR pts, low GFR pts were not prevented or delayed in getting cystectomy, and had comparable impact of NAC on GFR. For carefully selected pts with GFR &lt; 60 ml/min, cisplatin-based NAC is a treatment option, consistent with prior data.

Abstract P2-10-09: Clinical correlations of serum vitamin D in patients undergoing neoadjuvant systemic therapy and survival outcomes for operable breast cancer

Abstract Introduction: There has been increasing interest in the potential benefit of vitamin D to improve breast cancer outcomes. Pre-clinical studies suggest vitamin D enhances chemotherapy-induced cell death. We previously reported (Thomas A SABCS 2016) that low serum vitamin D levels were associated with not attaining a pathologic complete response (pCR) following breast cancer neoadjuvant chemotherapy (NAC). We report here the impact of vitamin D on survival parameters in an expanded cohort of patients. Methods: Patients from two Iowa registries who had serum vitamin D level measured before or during NAC were included. French patients enrolled in a previous study of the impact of NAC on vitamin D and bone metabolism were also eligible for this study. Vitamin D deficiency was defined as &amp;lt; 20 ng/mL. pCR was defined as no residual invasive disease in breast and lymph nodes. Survival was defined from the date of diagnosis to the date of relapse (PFS) or date of death (OS). Results: The study included 327 women. Median age was 51 years. Patients presented with HER2+, HR+/HER2- and triple negative (TN) tumors in 28.5%, 43.9% and 27.6% of the cases respectively. In this expanded cohort, vitamin D deficiency remained associated with the odds of not attaining pCR (OR 1.64; 95%CI: 1.02-2.66, p=0.04). Median follow-up was 5.33 years (range 0.5 to 9.8 years). Of these patients, there were 54 relapse and 52 deaths. In multivariate analysis, stage III disease, TN phenotype and the inability to achieve pCR were independently associated with a worse survival (Table 1). Table 1 PFS (Hazard Ratio, 95%CI)pOS (Hazard Ratio, 95%CI)pStage I - II1 1 III2.78 (1.56 – 4.95)0.0012.82 (1.57 - 5.05)0.001Tumor phenotype HR+/HER2-1 1 HER2+3.00 (1.28 – 7.06)0.0121.78 (0.76 – 4.08)0.174TN7.37 (3.26 – 16.69)&amp;lt; 0.0016.50 (3.07 – 13.76)&amp;lt; 0.001NAC response Non-pCR1 1 pCR0.19 (0.08 – 0.45)&amp;lt; 0.0010.22 (0.09 – 0.55)&amp;lt; 0.001Vitamin D &amp;lt; 20 ng/mL1 1 ≥ 20 ng/mL1.01 (0.57 – 1.78)0.971.03 (0.58 – 1.84)0.92 Vitamin D deficiency was not significantly associated with survival parameters in the general population; however a trend was seen in the TN population regarding the correlation with PFS (90 patients, 5-year PFS 60.4% vs. 72.3%, p=0.18). Conclusion: Vitamin D deficiency is associated with the inability to reach pCR in breast cancer undergoing NAC. A trend for worse survival was seen in the TN subgroup. The strong association between vitamin D deficiency and the inability to reach pCR warrant further evaluation in the TN subgroup. Prospective interventional studies are needed to elucidate if maintaining vitamin D levels during NAC, a highly modifiable variable, may be utilized to improve cancer outcomes, particularly in TN breast cancers. Citation Format: Viala M, Chiba A, Thezenas S, Delmond L, Lamy P-J, Mott SL, Schroeder MC, Thomas A, Jacot W. Clinical correlations of serum vitamin D in patients undergoing neoadjuvant systemic therapy and survival outcomes for operable breast cancer [abstract]. In: Proceedings of the 2017 San Antonio Breast Cancer Symposium; 2017 Dec 5-9; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2018;78(4 Suppl):Abstract nr P2-10-09.