Next generation sequencing of urothelial bladder cancer: Memorial Sloan Kettering Cancer Center experience in 454 patients.

2018 ◽  
Vol 36 (6_suppl) ◽  
pp. 469-469
Author(s):  
Sumit Isharwal ◽  
Francois Audenet ◽  
Esther N. Drill ◽  
Irina Ostrovnaya ◽  
Eugene J. Pietzak ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Tumor Stage ◽  
Urothelial Bladder Cancer ◽  
Primary Tumors ◽  
Free Survival ◽  
Urothelial Bladder ◽  
Cell Cycle Pathway ◽  
Generation Sequencing

469 Background: Genomic characterization of urothelial bladder cancer (UBC) may help to identify alterations associated with tumor stage, novel therapeutic targets and biomarkers to predict outcomes. Methods: 454 UBC patients were sequenced using next generation sequencing assay (MSK−IMPACT). 264 patients (123 NMIBC, 112 MIBC and 29 metastatic) were chemotherapy naïve primary tumors. Results: Patients whose primary tumors harbored TP53, RB1, TP53/MDM2, and cell cycle pathway alterations more frequently presented with advanced disease whereas those with tumors containing FGFR3, and RTK/RAS/RAF pathway alterations generally presented with NMIBC (all FDR < 0.001). TP53, RB1, TP53/MDM2, and cell cycle pathway alterations were associated with worse overall and metastasis free survival whereas FGFR3 alterations were associated with more favorable overall and metastasis free survival (all FDR < 0.05). RTK/RAS/RAF pathway alterations were associated with more favorable metastasis free survival (FDR = 0.01). MIBC with no DDR alterations, DDR alterations of unknown significance and DDR deleterious alterations had pathologic downstaging rates of 37%, 48% and 81% with platinum-based neoadjuvant chemotherapy (p = 0.013). Patients with ERCC2 mutations had significantly higher pathologic downstaging with platinum-based neoadjuvant chemotherapy compared to patients without ERCC2 mutations (p = 0.025). MIBC with DDR alterations had better overall survival with neoadjuvant chemotherapy compared to MIBC without DDR alterations (p = 0.04). Of note, MIBC cases with and without DDR alterations have similar overall survival in the absence of neoadjuvant chemotherapy (p = 0.78). Conclusions: TP53, RB1 and FGFR3 alterations as well as TP53/MDM2, cell cycle and RTK/RAS/RAF pathway alterations showed an association with tumor stage and patient outcomes. MIBC with DDR alterations had higher pathological downstaging as well as better overall survival compared to MIBC without DDR alterations with platinum−based neoadjuvant chemotherapy. In absence of neoadjuvant chemotherapy, MIBC with and without DDR alterations have similar patient outcomes.

Comparison of Survival Outcomes for Axillary Surgery Extent Based on Intraoperative Sentinel Lymph Node Biopsy Result After Neoadjuvant Chemotherapy for Breast Cancer

2021 ◽  
Author(s):  
Jung Whan Chun ◽  
Jisun Kim ◽  
Il Yong Chung ◽  
Beom Seok Ko ◽  
Hee Jeong Kim ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Sentinel Lymph Node ◽  
Neoadjuvant Chemotherapy ◽  
Axillary Recurrence ◽  
Recurrence Free Survival ◽  
Free Survival ◽  
Axillary Surgery ◽  
Distant Metastasis Free Survival

Abstract PurposeTo investigate the survival difference between limited axillary surgery and full axillary lymph node dissection (ALND) in patients with 1-3 positive sentinel lymph node biopsies (SLNBs) after neoadjuvant chemotherapy (NAC).MethodWe retrospectively analyzed data from 676 patients who underwent surgery between 2007 and 2017 with cT1-4, cN0-3, cM0 breast cancer at the time of diagnosis and 1-3 positive SLNBs after NAC. The patients received either SLNB only or completed level I or II ALND based on SLNB results. After propensity score matching, 483 patients who had undergone SLNB only (n=188) and ALND (n=295) were included. We examined overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival and compared them between the subgroups.ResultAt a median follow-up of 59.4 months, no significant statistical difference was observed in overall survival, axillary recurrence-free survival, regional recurrence-free survival, and distant metastasis-free survival between SLNB only and ALND. No significant differences were observed in the 5-year axillary recurrence-free survival (93.1% vs. 94.0%, hazard ratio [HR]=0.94, 95% confidence interval [CI]=0.43-2.05, p=0.876) and 5-year overall survival (97.7% vs. 97.3%, HR=1.65, 95% CI=0.58-4.65, p=0.347) between the two groups.ConclusionOur analysis suggests that SLNB alone may be a possible option for patients with 1-3 sentinel node-positive breast cancer following NAC without significant compromise of recurrence or overall survival.

Elevated expression of ASF1B correlates with poor prognosis in human lung adenocarcinoma

2021 ◽  
Vol 18 (2) ◽  
pp. 115-127
Author(s):  
Zhenxing Feng ◽  
Jiao Zhang ◽  
Yafang Zheng ◽  
Qingzhang Wang ◽  
Xiaochuan Min ◽  
...  
Keyword(s):  
Overall Survival ◽  
Lung Adenocarcinoma ◽  
Tumor Development ◽  
Tumor Stage ◽  
Gene Expression Omnibus ◽  
The Cancer Genome Atlas ◽  
Advanced Tumor Stage ◽  
Aberrant Expression ◽  
Free Survival ◽  
Advanced Tumor

Aim: ASF1 is involved in tumorigenesis. However, its possible role in lung adenocarcinoma (LUAD) is unclear. This study thus explored the role of ASF1A and ASF1B in LUAD. Materials & methods: Data from The Cancer Genome Atlas and Gene Expression Omnibus were employed to investigate ASF1A and ASF1B expression and its roles in LUAD prognosis. Immunohistochemistry was applied to determine the protein expression of ASF1B of 30 LUAD patients. Results: The upregulation of ASF1B in tumor tissues is associated with worse overall survival and progress-free survival and is correlated with advanced tumor stage and tumor development. However, aberrant expression of ASF1A was not found in LUAD and ASF1A was not related to patients’ overall survival and progress-free survival. Conclusion: ASF1B could be a promising prognostic and therapeutic biomarker in LUAD.

scholarly journals Large-Scale Analysis of Cell Cycle Regulators in Urothelial Bladder Cancer Identifies p16 and p27 as Potentially Useful Prognostic Markers

Pathobiology ◽  
2008 ◽  
Vol 75 (1) ◽  
pp. 25-33 ◽  
Author(s):  
Andrea Brunner ◽  
Irmgard Verdorfer ◽  
Martina Prelog ◽  
Christina Mayerl ◽  
Gregor Mikuz ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Bladder Cancer ◽  
Large Scale ◽  
Prognostic Markers ◽  
Scale Analysis ◽  
Cell Cycle Regulators ◽  
Urothelial Bladder Cancer ◽  
Large Scale Analysis ◽  
Urothelial Bladder

Measuring response to neoadjuvant chemotherapy in high-grade serous tubo-ovarian carcinoma: an analysis of the correlation between CT imaging and chemotherapy response score

2019 ◽  
Vol 29 (5) ◽  
pp. 929-934 ◽  
Author(s):  
Meabh McNulty ◽  
Adarsh Das ◽  
Paul A Cohen ◽  
Andrew Dean
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Partial Response ◽  
Stable Disease ◽  
Progression Free Survival ◽  
Chemotherapy Response ◽  
High Grade ◽  
Free Survival ◽  
Radiological Response ◽  
Response Score

IntroductionResponse to neoadjuvant chemotherapy is measured by CT and the decision to proceed with interval surgery is made on the radiological response after two or three cycles of therapy. The Chemotherapy Response Score grades histological tumor regression in omental metastases resected at interval surgery and is associated with progression-free survival and overall survival. It is uncertain whether radiological response is associated with prognosis and whether radiological response predicts Chemotherapy Response Score.To assess if radiological response is associated with progression-free survival and overall survival. Additionally, to investigate whether radiological response predicts the Chemotherapy Response Score.MethodsRetrospective cohort study of patients with high-grade serous ovarian cancer treated with neoadjuvant chemotherapy. Radiological response was assessed by comparing CT imaging at baseline and after neoadjuvant chemotherapy using RECIST (Response Evaluation Criteria In Solid Tumors) and classified as stable disease, partial response, complete response, or progressive disease. Survival analysis was performed using Cox proportional-hazard models and the log-rank test.ResultsA total of 71 patients met the inclusion criteria. Of these, 51 had pre- and post-neoadjuvant chemotherapy CT scans available for analysis. Radiological response was not associated with progression-free survival or overall survival on univariate analysis (stable disease vs partial response; HR for progression-free survival 1.15; 95% CI 0.57 to 2.32; p = 0.690; HR for overall survival 1.19; 95% CI 0.57 to 2.46; p = 0.645). In a multivariate model, radiological response was not associated with either progression-free survival (stable disease vs partial response; HR=1.19; 95% CI 0.498 to 2.85; p = 0.694) or overall survival (stable disease vs partial response; HR=0.954; 95% CI 0.38 to 2.40; p = 0.920). There was a significant association between the Chemotherapy Response Score and radiological response (p = 0.005).DiscussionA partial response and stable disease on radiological assessment after neoadjuvant chemotherapy in women with advanced high-grade serous ovarian cancer were not associated with survival, despite having a correlation with the Chemotherapy Response Score.

Neoadjuvant chemotherapy in urothelial bladder cancer: impact of regimen and variant histology

2016 ◽  
Vol 12 (15) ◽  
pp. 1795-1804 ◽  
Author(s):  
Hristos Z Kaimakliotis ◽  
M Francesca Monn ◽  
Jane S Cho ◽  
Jose A Pedrosa ◽  
Noah M Hahn ◽  
...  
Keyword(s):  
Bladder Cancer ◽  
Neoadjuvant Chemotherapy ◽  
Urothelial Bladder Cancer ◽  
Urothelial Bladder ◽  
Variant Histology

Twenty-one cases of blastic plasmacytoid dendritic cell neoplasm: focus on biallelic locus 9p21.3 deletion

Blood ◽  
2011 ◽  
Vol 118 (17) ◽  
pp. 4591-4594 ◽  
Author(s):  
Marco Lucioni ◽  
Francesca Novara ◽  
Giacomo Fiandrino ◽  
Roberta Riboni ◽  
Daniele Fanoni ◽  
...  
Keyword(s):  
Cell Cycle ◽  
Overall Survival ◽  
Dendritic Cells ◽  
Statistical Analysis ◽  
Dendritic Cell ◽  
Clinical Presentation ◽  
Plasmacytoid Dendritic Cell ◽  
Tumor Stage ◽  
Comparative Genomic ◽  
Cell Neoplasm

Abstract Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare and aggressive malignancy derived from precursors of plasmacytoid dendritic cells. We analyzed 21 cases with array-based comparative genomic hybridization (aCGH). Complete or partial chromosomal losses largely outnumbered the gains, with common deleted regions involving 9p21.3 (CDKN2A/CDKN2B), 13q13.1-q14.3 (RB1), 12p13.2-p13.1 (CDKN1B), 13q11-q12 (LATS2), and 7p12.2 (IKZF1) regions. CDKN2A/CDKN2B deletion was confirmed by FISH. This scenario argues for disruption of cell cycle at G1/S transition, representing a genetic landmark of BPDCN, and possibly contributing to its pathogenesis. Statistical analysis of overall survival in our series highlighted an association of poor outcome with biallelic loss of locus 9p21.3. We suggest that, in the absence of reliable parameters for predicting prognosis in BPDCN other than age, tumor stage, and/or clinical presentation, simple methods, such as FISH for CDKN2A/CDKN2B, could help to identify the most aggressive cases.

Radiographic tumor response in pediatric patients with newly diagnosed localized (LOC) or metastatic (MET) Ewing’s sarcoma (EWS) following neoadjuvant chemotherapy

2007 ◽  
Vol 25 (18_suppl) ◽  
pp. 20008-20008
Author(s):  
M. K. Chuk ◽  
F. M. Balis ◽  
C. Mackall ◽  
D. Hawkins ◽  
N. Avila ◽  
...  
Keyword(s):  
Overall Survival ◽  
Neoadjuvant Chemotherapy ◽  
Local Control ◽  
Pediatric Patients ◽  
Standard Treatment ◽  
Tumor Response ◽  
Newly Diagnosed ◽  
Primary Tumors ◽  
Who Criteria ◽  
Radiographic Response

20008 Background: Standard treatment for EWS includes vincristine, doxorubicin, cyclophosphamide (VDC) alternating with ifosfamide and etoposide (IE). Using this therapy, overall survival is 70% in patients with LOC EWS and 30% in patients with MET EWS. We compared the radiographic response to VDC and IE in patients with LOC or MET EWS. Methods: We conducted a randomized trial comparing pegfilgrastim to filgrastim in patients treated with VDC (cycles 1, 2, 5, 9, 11, 13) and IE (cycles 3, 4, 6–8, 10, 12, 14). Local control with radiation or surgery was initiated after cycle 5. We assessed radiographic response after VDC (C1,2) and IE (C3,4) using 1-dimensional (RECIST) and 2-dimensional (WHO) criteria. Measurements were performed using MEDx. Results: Twenty-one patients with EWS, median age 20y (6–25y), were enrolled; 16 were evaluable for this analysis. Primary tumors were in extremity (n=5) or central axis (n=11). Eight patients had MET disease (pulmonary only, n=4). Median (range) decrease in tumor size by WHO after C4 was 61% (40–92%) for LOC and 83% (47–94%) for MET. Decrease by treatment is presented in the table . Overall responses after 4 cycles for LOC patients were 5 PR, 3 SD using RECIST, and 6 PR, 2 SD using WHO. For MET patients, overall responses were the same using RECIST and WHO, 7 PR, and 1SD. Conclusion: Patients with MET EWS responded as well as those with LOC EWS after 4 cycles of neoadjuvant chemotherapy. Similar overall response was demonstrated using RECIST or WHO. Tumor response after VDC was greater than after IE, possibly due to sequence of administration, but patients had continued tumor response with IE. [Table: see text] No significant financial relationships to disclose.

Feasibility and potential benefit of neoadjuvant chemotherapy for colorectal liver metastasis: A single-centered retrospective study.

2011 ◽  
Vol 29 (4_suppl) ◽  
pp. 465-465
Author(s):  
K. Kataoka ◽  
A. Kanazawa ◽  
A. Nakajima ◽  
A. Yamaguchi ◽  
S. Tuyuki ◽  
...  
Keyword(s):  
Overall Survival ◽  
Postoperative Complications ◽  
Neoadjuvant Chemotherapy ◽  
Liver Volume ◽  
Disease Free Survival ◽  
Combination Regimen ◽  
Remnant Liver ◽  
Free Survival ◽  
Median Disease Free Survival ◽  
Disease Free

465 Background: Recently, several papers have reported the advantage of neoadjuvant chemotherapy for liver limited metastatic colorectal cancer. In these papers, most study groups used criteria for non-resectability due to size and/or number of metastases. Our criteria for resectability of colorectal liver metastases (CLM) depends on the size of remnant liver volume (>30%) and expected function after the removal of all metastases. Then, we assessed the feasibility and potential benefits of chemotherapy administered before surgery to patients with CLM retrospectively. Methods: From January 2007 to April 2010, 67 chemotherapy-naive patients were diagnosed as CLM without extra-hepatic metastases. After chemotherapy, we assessed the resectability with radiological examination.Then, each case was divided in two groups, resected group and unresected group. Overall survival, median disease-free survival and postoperative complications were analyzed. Results: 63 patients received oxaliplatin-based combination regimen and 4 patients other regimen. 30 patients (resected group) received R0 resection and 37 patients (unresected group) were considered as unresectable. No serious postoperative complications were observed. Overall survival was significantly higher in resected group than in unresected group (42.3 month and 29.1 month; P<0.001). Median disease-free survival was 18.8 months in resected group (95% CI:3.02 to 31.33). According to our retrospective review, resectable cases increased from 28 of 67 patients at baseline to 33 after chemotherapy (including 3 cases considered as CR after chemotherapy only). Conclusions: Intensive treatment with neoadjuvant chemotherapy for CLM is well tolerated. Curative surgery improved significantly overall survival in patients with CLM. Neoadjuvant chemotherapy such as mFOLFOX6 may lead to increased resectability but do not increase postoperative complications. For most patients with resectable CLM, neoadjuvant chemotherapy should be considered the standard treatment. No significant financial relationships to disclose.

Salvage gastrectomy for unresectable advanced gastric cancer after combination chemotherapy with docetaxel, cisplatin, and S-1.

2013 ◽  
Vol 31 (15_suppl) ◽  
pp. e15113-e15113
Author(s):  
Kei Hosoda ◽  
Keishi Yamashita ◽  
Shinichi Sakuramoto ◽  
Hiroaki Mieno ◽  
Katsuhiko Higuchi ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Overall Survival ◽  
Lymph Node ◽  
Advanced Gastric Cancer ◽  
Univariate Analysis ◽  
Pancreatic Head ◽  
Progression Free Survival ◽  
Hematologic Toxicity ◽  
Primary Tumors ◽  
Free Survival

e15113 Background: The prognosis for patients with unresectable advanced gastric cancer treated with chemotherapy alone is extremely poor. We have evaluated the safety and efficacy of salvage gastrectomy following chemotherapy with docetaxel, cisplatin, and S-1 (DCS) in patients with unresectable advanced gastric cancer. Methods: We evaluated 30 patients with unresectable advanced gastric adenocarcinoma whose lesions were down-staged by DCS chemotherapy and who underwent salvage gastrectomy with lymph node dissection from 2006 to 2012, when visible lesions were judged resectable. We retrospectively reviewed their medical records to identify factors that would influence overall survival. Results: Of the 30 patients, 17 had extra-regional lymph node metastases, 5 had liver metastases, 9 had peritoneal dissemination and 6 had pancreatic head invasion prior to DCS chemotherapy. Of the 30 patients, 23, 3, and 4 underwent R0, R1, and R2 resection, respectively. No in-hospital deaths or reoperations occurred. Pathological evaluation of primary tumors revealed grades 3, 2, 1b, 1a, and 0 tumor regression in 4, 9, 7, 7, and 2 patients, respectively. Median progression-free survival was 19 months.Two-year progression-free survival and overall survival rates were 45% and 65%, respectively. Of 17 patients with target tumors, 15 had partial responses, making the overall response rate 88%. The most common grade 3/4 hematologic toxicity was neutropenia (56%); all treatment-related toxicities were resolved, and no patient died of toxicity-related causes. Univariate analysis showed that R1/2 surgery (p<0.001), diffuse type histology (p=0.054), histological grade 0/1a/1b following chemotherapy (p<0.033), ypN3 (p<0.001) and yply2/3 (p=0.003), were significantly prognostic of reduced overall survival. A multivariate proportional hazard model found that ypN3 (p=0.003) was the sole independent prognostic factor. Conclusions: Salvage gastrectomy after DCS chemotherapy was safe and effective in patients with unresectable advanced gastric cancer. Lymph node metastasis after chemotherapy was significantly prognostic of poor prognosis, suggesting the need for further treatment.

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