Myeloid-Derived Suppressor Cells in Nonmetastatic Urothelial Carcinoma of Bladder Is Associated With Pathologic Complete Response and Overall Survival

2020 ◽  
Vol 18 (6) ◽  
pp. 500-508 ◽  
Author(s):  
Jaleh Fallah ◽  
Claudia Marcela Diaz-Montero ◽  
Patricia Rayman ◽  
Wei Wei ◽  
James H. Finke ◽  
...  
Keyword(s):  
Overall Survival ◽  
Urothelial Carcinoma ◽  
Pathologic Complete Response ◽  
Suppressor Cells ◽  
Complete Response ◽  
Myeloid Derived Suppressor Cells ◽  
Urothelial Carcinoma Of Bladder

scholarly journals Impact of Neoadjuvant Chemotherapy for Upper Tract Urothelial Carcinoma: A Population Based Analysis

2021 ◽  
pp. 1-12
Author(s):  
Siv Venkat ◽  
Patrick J. Lewicki ◽  
Spyridon P. Basourakos ◽  
Douglas S. Scherr
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Urothelial Carcinoma ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Upper Tract Urothelial Carcinoma ◽  
Clinical Predictors ◽  
Upper Tract ◽  
Node Positive ◽  
Node Positive Disease

BACKGROUND AND OBJECTIVES: We examined pathologic complete response (pCR) and pathologic downstaging (pDS) rates after neoadjuvant chemotherapy (NAC) in high-risk upper tract urothelial carcinoma, as well as their predictors. We further sought to determine their effects on overall survival and examine prognosticators of survival after NAC. METHODS: The National Cancer Database was used to identify all patients from 2004 to 2016 with nonmetastatic high grade upper tract urothelial carcinoma who received NAC followed by nephroureterectomy. pCR and pDS rates were examined, and univariate and multivariate logistic regression was performed to identify clinical predictors. Kaplan-Meier and Cox proportional hazard methods were used to estimate overall survival. RESULTS: 309 patients met inclusion criteria. 27 patients (8.74% ) had pCR, and 92 (29.77% ) had pDS. pCR and pDS rates for N+ subgroup were 6.82% and 47.73% respectively, and for N0 subgroup, 9.50% and 22.62%. Female sex (OR 2.94, p = 0.010) was the only predictor of pCR. Node-positive disease (cN1 vs. cN0: OR 6.40, p <  0.001; cN2 vs. cN0: OR 7.46, p <  0.001) was a positive predictor of pDS, and the presence of lymphovascular invasion (LVI) (OR 0.14, p <  0.001) was a negative predictor of pDS. The median OS for all patients was 45.5 months. pCR and pDS were both associated with improved OS, (p <  0.001 for both); median was 99.1 months for both. LVI was the strongest negative prognostic factor for OS (HR 2.85, p <  0.001). CONCLUSIONS: Overall pathological complete response and downstaging rates were 8.74% and 29.77% respectively after multi-agent neoadjuvant chemotherapy. Node-negative and node-positive disease had equivalent rates of complete response, but node-positive disease had a significantly higher rate of downstaging. The presence of LVI was associated with worse overall survival.

Association of total neoadjuvant therapy with favorable clinical outcomes in patients with locally advanced esophageal and gastroesophageal junction adenocarcinomas (LA-GEJ CA).

2021 ◽  
Vol 39 (3_suppl) ◽  
pp. 231-231
Author(s):  
Lauren Jurkowski ◽  
Aditya Varnam Shreenivas ◽  
Sakti Chakrabarti ◽  
Mandana Kamgar ◽  
James P. Thomas ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Therapy ◽  
Clinical Outcomes ◽  
Gastroesophageal Junction ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Metabolic Imaging ◽  
R0 Resection ◽  
Curative Intent

231 Background: Both peri-operative chemotherapy and neoadjuvant chemoradiation have been shown to improve outcomes in patients (pts) with LA-GEJ CA compared to surgery alone. Rates of post-operative chemotherapy delivery remain suboptimal. Total neo-adjuvant therapy (TNT) in LA-GEJ CA - induction chemotherapy (IC) followed by concurrent chemoradiation (CRT) - may improve systematic delivery of neoadjuvant therapy and result in favorable clinical outcomes. Methods: We retrospectively reviewed medical records of 135 pts with LA-GEJ CA at our institution between 2/2007 and 11/2019; pertinent clinical data were abstracted with Institutional Review Board approval. Patients treated with IC and curative-intent CRT with ≥40 Gy dose of radiation for adenocarcinoma were included in this analysis (N = 59). Doublet or triplet IC regimens utilizing 5-Flurouracil(5-FU), Cisplatin/Oxaliplatin and Docetaxel were commonly administered while combinations of Carboplatin +Paclitaxel or 5-FU + Oxaliplatin were used in CRT. Clinical complete response (CCR) was defined as metabolic imaging and endoscopic biopsies negative for residual malignancy after completion of TNT. Patients were followed from diagnosis to recurrence and overall survival. Survival probabilities were estimated using the Kaplan-Meier method and compared between groups using a log-rank test. Results: Out of 59 evaluable pts, 69% were clinical stage T3, 71% were node positive. 37 pts (63%) underwent surgery, R0 resection rate was 89% (33/37), pathologic complete response (pCR) rate was 19% (7/37). Among the pts who did not undergo surgery, 41% (9/22) opted to forego surgery since they attained a CCR. For the entire cohort, median Disease-Free Survival (mDFS), median Overall Survival (mOS), and 3-yr OS were 2.4 yrs, 4.7 yrs, and 67% respectively. Pts who did not undergo surgery had a mDFS, mOS, and 3-yr OS of 1.5 yrs, 4.2 yrs, and 59% respectively. Median DFS, mOS, and 3-yr OS of patients who underwent surgery were 3.5 yrs, 5.8 yrs and 72% respectively. Patients who achieved a CCR and opted to forego surgery (N = 9) had a 3 -yr DFS of 42% vs 83% for pts (N = 7) who demonstrated a pCR after curative intent tri-modality therapy. (P = 0.0099) Interestingly, the same group that achieved CCR and opted out of surgery had 3yr OS of 89% vs 83% of those who demonstrated a pCR (p = 0.0042). Conclusions: TNT for pts with LA-GEJ CA is associated with high rates of R0 resection as well as excellent DFS and OS compared to historical controls, warranting prospective evaluation. The remarkable DFS and OS in patients who opted to forego surgery due to achieving CCR is reflective of the local and systemic control rendered by this approach. Careful characterization and close longitudinal follow-up of patients who achieve CCR may help identify a subgroup of LA-GEJ CA pts who may benefit from surgery sparing approaches.

Evaluation of blood and tissue myeloid derived suppressor cells (MDSC), clinicopathologic factors, and pathologic response in urothelial carcinoma (UC).

2016 ◽  
Vol 34 (15_suppl) ◽  
pp. e16010-e16010
Author(s):  
Moshe Chaim Ornstein ◽  
C. Marcela Diaz-Montero ◽  
Pat A. Rayman ◽  
Paul Elson ◽  
Samuel Haywood ◽  
...  
Keyword(s):  
Urothelial Carcinoma ◽  
Suppressor Cells ◽  
Pathologic Response ◽  
Myeloid Derived Suppressor Cells ◽  
Clinicopathologic Factors

Factors predictive of tumor recurrence and overall survival in patients with esophageal cancer who have pathologic complete response after neo-adjuvant therapy.

2016 ◽  
Vol 34 (4_suppl) ◽  
pp. 170-170
Author(s):  
Alexandra Gangi ◽  
Sarah E. Hoffe ◽  
Jessica M. Frakes ◽  
Khaldoun Almhanna ◽  
Luis Pena ◽  
...  
Keyword(s):  
Overall Survival ◽  
Esophageal Cancer ◽  
Neoadjuvant Therapy ◽  
Recurrent Disease ◽  
Systemic Disease ◽  
Cell Cancer ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Specific Information ◽  
Patient Demographics

170 Background: Pathologic complete response (pCR) to neoadjuvant therapy is presumably associated with favorable outcomes in patients (pts) with esophageal cancer, but reported survival rates vary. This study evaluates patterns of recurrence after curative esophagectomy and identifies factors predictive of recurrent disease and overall survival (OS) in patients with pCR. Methods: An IRB-approved, retrospective review of a prospective esophageal cancer database was conducted. Patient demographics, perioperative data, and outcomes were examined. Recurrences were classified as locoregional (LR) or systemic. Cox regression model and Kaplan–Meier (KM) plots were used for survival analysis. Results: 837 pts with invasive esophageal cancer treated at a single institution from 1994 to 2013 were identified. 176 pts underwent neoadjuvant therapy followed by surgery and had pCR. Of these, 93.7% had adenocarcinoma and 6.3% had squamous cell cancer. Mean age was 56.6 and most pts were white (96.6%) males (79.5%). Median follow up was 42.6 months. 95 pts were treated before 2007 and 81 after. Most pts (85%) underwent transthoracic esophagectomy. All 176 pts received chemotherapy and radiation; dose-specific information was available on 144 pts, of whom most received 50.4 Gy (45%). 170 pts had recurrence data available: 39 (22.9%) had recurrent disease at a mean of 18.3 months; 5 (2.9%) with LR and 34 (20%) with systemic disease. On multivariate analysis, when evaluating patient demographics, pretreatment stage, type of surgery, type of chemotherapy, and number of lymph nodes resected, only pretreatment stage was associated with recurrence (p = 0.04). Median time to recurrence was 26.3 months for LR disease and 10.9 months for systemic disease (p = 0.3). KM estimates determined that pre-treatment stage and time of treatment ( < 2007 or ≥ 2007) were predictive of improved OS (p < 0.01, = 0.03). Conclusions: The incidence of disease recurrence in pts who experience pCR is low. The pretreatment stage and time of treatment were independent predictors of improved OS. Enhancing treatment strategies to maximize pCR would improve outcomes in pts with esophageal cancer.

Association of adjuvant chemotherapy with improved overall survival for patients with locally advanced rectal cancer (LARC) who achieve a pathologic complete response (pCR) to neoadjuvant chemoradiation (nCRT).

2017 ◽  
Vol 35 (4_suppl) ◽  
pp. 716-716
Author(s):  
Danish Shahab ◽  
Emmanuel M. Gabriel ◽  
Kristopher Attwood ◽  
Valerie Francescutti ◽  
Wen Wee Ma ◽  
...  
Keyword(s):  
Rectal Cancer ◽  
Overall Survival ◽  
Adjuvant Chemotherapy ◽  
Adjuvant Therapy ◽  
Locally Advanced ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Neoadjuvant Chemoradiation ◽  
Comorbidity Score ◽  
N Stage

716 Background: 15-20% of patients with locally advanced rectal adenocarcinoma (LARC) achieve a pathologic complete response (pCR) following neoadjuvant chemoradiation (nCRT). The role of adjuvant chemotherapy has been questioned. Methods: Patients with rectal cancer receiving nCRT in the National Cancer Data Base (NCDB) 2006-2013 data set were evaluated. The primary outcome was overall survival (OS). The association between OS and patient characteristics were examined using multivariable Cox regression models. Results: 2,903 patients were identified who achieved a pCR. The median follow up was 43.2 months. 2,102 received nCRT and 789 received nCRT + adjuvant chemotherapy. Factors significantly associated with OS included age (p<0.001), gender (p=0.011), Charlson-Deyo comorbidity score (CDI) (p<0.001), grade (p=0.029), clinical T stage (p=0.030), and CEA negativity (p=0.002), but not nodal status. The 3-year OS rate was 94% in the adjuvant therapy group as compared to 84% in the nCRT alone group (p<0.001). In considering clinical N-stage, the benefit was comparable for both N+ and N- tumors. Adjuvant chemotherapy was more likely to be given for younger patients (age < 60), lower comorbidity score, higher grade, positive CEA status, higher clinical T stage, and higher clinical N stage. When stratifying by these factors, similar benefits in OS were observed in the adjuvant cohort. Conclusions: Following nCRT and achievement of a pCR, the receipt of adjuvant chemotherapy is associated with improved OS. Patients receiving adjuvant therapy were more likely to be younger and have a low CDI, but have more advanced stage disease. Thus, a selection bias may be present. Nonetheless, in the setting of the already excellent outcome associated with pCR, the additional benefit of adjuvant chemotherapy should be weighed against toxicity.

Evolution of the myeloid-derived suppressor cells in advanced breast cancer and comparative analysis with a healthy population cohort.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. 2543-2543
Author(s):  
Natalia Palazón-Carrión ◽  
Carlos Jiménez-Cortegana ◽  
Esther Holgado ◽  
Josefina Cruz Jurado ◽  
Jose Luis Alonso Romero ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Advanced Breast Cancer ◽  
Peripheral Blood ◽  
Suppressor Cells ◽  
Complete Response ◽  
Advanced Breast ◽  
Healthy Population ◽  
Myeloid Derived Suppressor Cells ◽  
Tumor Subtypes ◽  
Disease Stabilization

2543 Background: High levels of myeloid-derived suppressor cells (MDSCs) seem a negative prognostic factor in advanced breast cancer (ABC) patients (pts). Preclinical studies suggest an immunomodulatory effect of some classical anti-tumor agents through alteration of MDSCs homeostasis. We analyzed the association of MDSCs and clinical evolution of ABC pts, taking into account the systemic treatment (tx) modulation of MDSCs levels in pts from two studies (“A”: GEICAM/2015-04 PANGEA-BREAST, NCT03025880 “Efficacy and Safety of Pembrolizumab and Gemcitabine in HER2-negative ABC”, and “B”: PI-0502-2014 “Peripheral blood analyses of immune response induced by 1st line tx of ABC according to clinical guidelines”). Methods: MDSCs (CD33+ CD11b+) levels were determined by flow-cytometry in peripheral blood samples at three time points (basal, at cycles 3 and 6) from: 39 HER2-negative heavily pretreated pts from study “A”, 43 non-pretreated pts (all subtypes) from study “B” and 20 women from a healthy cohort (HC), with no cancer diagnosis. MDSCs levels from the different cohorts were compared and correlated with pts with Clinical Benefit (CB: partial/complete response + disease stabilization) vs pts with Progressive Disease (PD). Results: Tx response was assessed in 33 pts (85%) from study “A” and 39 pts (91%) from study “B”. CB was observed in 11 pts (28%) from study “A” and in 34 (79%) from study “B” while PD was observed in 22 pts (56%) from study “A” and in 5 (12%) from study “B”. Basal MDSCs levels were significantly higher in ABC pts (studies “A”+”B”) than in HC (15.95 vs 0.81 cells/µl, p = 0.009). At cycle 6, MDSCs were considerably lower in pts with CB vs DP (2.90 vs 13.75 cells/µl, p < 0.001). This decrease was more pronounced in study “B” than in study “A” pts (p < 0.001 vs p = 0.074, respectively), probably due to differences in number of events, tumor subtypes and tx between both studies. Conclusions: Our results suggest that ABC pts show alterations in MDSCs and that their decrease along tx may have a positive predictive value, highlighting the importance that immune-competent status may play in the evolution of ABC. MDSCs may represent a target for therapeutic purposes in ABC.

Impact of angiotensin inhibitors on pathologic complete response with neoadjuvant chemotherapy (NAC) for muscle-invasive bladder cancer (MIBC).

2021 ◽  
Vol 39 (6_suppl) ◽  
pp. 432-432
Author(s):  
Jonathan Thomas ◽  
Gregory Russell Pond ◽  
Catherine Curran ◽  
Dory Freeman ◽  
Praful Ravi ◽  
...  
Keyword(s):  
Overall Survival ◽  
Bladder Cancer ◽  
Angiotensin Receptor Blockers ◽  
Pathologic Complete Response ◽  
Complete Response ◽  
Invasive Bladder Cancer ◽  
Antitumor Effects ◽  
Muscle Invasive Bladder Cancer ◽  
Pathologic Features ◽  
Muscle Invasive

432 Background: The renin-angiotensin system (RAS) is involved in regulation of angiogenesis, cell proliferation, desmoplasia and immunosuppression. Angiotensin converting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) may have antitumor effects partly by inhibiting transforming growth factor (TGF)-β, a major resistance mechanism in bladder cancer. Methods: Patients (pts) with muscle invasive bladder cancer (MIBC) treated or not treated with ACEi/ARB while receiving preceding radical cystectomy (RC) were assessed for pathologic complete response (pCR) defined as pT0N0 and overall survival (OS). Pathologic features, performance status, clinical stage, type and number of cycles of NAC, and presence of grade ≥3 toxicities were collected retrospectively. The Kaplan-Meier method was used to estimate overall survival (OS). Logistic and Cox regression was used to explore factors potentially prognostic for pCR and OS respectively. Results: 187 patients received NAC followed by RC. The mean age at the time of NAC was 65. 71% were male and 29% were female. Of the 187 patients, 61% received Cisplatin/Gemcitabine and 28.3% received dose dense MVAC. Of patients receiving NAC, 53 (28%) had a pCR. The 5-year OS was 64%. There were 41 (21.9%) patients taking an ACEi and 24 (12.8%) patients taking an ARB at the start of NAC. Of the 41 patients who took an ACEi, 17 (41.5%) had a pCR; of the 146 patients who did not take an ACEi, 36 (24.7%) had a pCR. ACEi intake during NAC was the only factor associated with pCR on multivariable analysis (odds ratio of 2.17 [95% CI 1.05-4.48] p = 0.037). pCR was the only factor shown to be associated with significantly improved OS (Hazard Ratio 0.18 [95% CI 0.07-0.45] p = < 0.001). After adjusting for pCR, ACEi was not significantly prognostic of OS (HR = 1.12, 95% CI = 0.60 to 2.09, p = 0.72). ARB intake while receiving NAC was not associated with pCR or OS. Conclusions: ACEi intake was associated with significantly increased pCR in patients with MIBC receiving NAC, and pCR was the only significant factor associated with OS. We hypothesize that ACEi may augment the activity of NAC and increase pCR, which translates to improved OS. ACEi intake was not associated with improvement in OS potentially due to competing causes of mortality in patients requiring ACEi. Our data requires validation.

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