Identifying predictive biomarkers for metastatic progression in stage I and II clear cell renal cell carcinoma.

2019 ◽  
Vol 37 (7_suppl) ◽  
pp. 631-631
Author(s):  
Neal J Murphy ◽  
Andrew Shih ◽  
Zachary Kozel ◽  
Paras Shah ◽  
Oksana Yaskiv ◽  
...  
Keyword(s):  
Gene Expression ◽  
Early Stage ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Stage I ◽  
Stage Ii ◽  
Cell Renal Cell Carcinoma ◽  
Early Stage Disease ◽  
Stage Disease ◽  
Experimental Group

631 Background: For most clear cell renal cell carcinoma (ccRCC) patients with early stage disease, surgical resection offers definitive cure. However, for the small percentage of tumors that metastasize, analyzing gene expression profiles from the primary site at the time of nephrectomy can serve as a model to understand the molecular aberrations behind a metastatic phenotype. Differences in gene expression profiles between patients with Stage I and II ccRCC who experience metastasis versus patients who maintain cure after surgery may help elucidate significant molecular targets and stratify patients at higher risk for metastasis. Methods: Nineteen Stage I and twenty Stage II ccRCC tumors preserved in FFPE blocks after nephrectomy were included in this study. Patients were matched for age, gender, tumor size and grade. In both stages, approximately half the patients that experienced metastasis within 5 years of surgery were part of the experimental group, whereas the control group had > 5 years of follow-up without evidence of disease. Extracted RNA for Stage I patients was sequenced using Illumina TruSeq RNA Access Library. Gene counts were assessed by ht-seq counts and differential expression using DESeq2. Significant genes found were validated in the Stage II group using RT-qPCR. Results: In the Stage I experimental group, statistically significant upregulation of several genes associated with unfavorable prognosis in RCC were found: COL1A1, NUMBL, and STEAP3. Random forest classification accurately separated Stage I control versus experimental patients based on expression of COL1A1. Affected genes were consistent with molecular changes seen in TCGA analysis. In the Stage II group, a double-blinded analysis correctly identified the clinical outcome for the majority of the patients using qPCR expression of COL1A1, NUMBL, and STEAP3. Conclusions: Differences in gene expression profiles harbored in the primary site of early stage ccRCC may be employed to predict patients at high risk for developing metastasis. Validating these findings in a larger study carries the potential to better understand mechanisms of metastasis and identify an at risk cohort of patients with early stage disease.

Neuroendocrine carcinoma of the cervix: A single institution’s experience.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. e15585-e15585
Author(s):  
Megan Preston ◽  
Georgia Anne-Lee McCann ◽  
David M. O'Malley ◽  
Christina Boutsicaris ◽  
Larry J. Copeland ◽  
...  
Keyword(s):  
Adjuvant Therapy ◽  
Metastatic Disease ◽  
Survival Data ◽  
Early Stage ◽  
Stage I ◽  
Stage Ii ◽  
Advanced Stage ◽  
Single Institution ◽  
Early Stage Disease ◽  
Stage Disease

e15585 Background: Neuroendocrine carcinomas (NEC) of the cervix comprise only 2% of all cervical cancers. As a result, prospective data is limited and treatment guidelines rely on literature from lung NEC. The objective of this study was to examine and report on our experience in the management of this rare, aggressive disease. Methods: This was an IRB-approved, single-institution, retrospective review. Study criteria included patients with cervical NEC diagnosed between 1990-2011. Demographic, treatment and survival data was collected. Progression-free survival (PFS) and overall survival (OS) was defined as the time from date of initial treatment until progression or death respectively, or date of last contact. Results: A total of 24 patients met inclusion criteria. The median age at diagnosis was 43. Median PFS was 13.6 months and median OS was 16.4 months. The majority of patients had advanced-stage disease (61% stage II-IV, 39% stage I). Of the 9 patients with stage I disease, 4 were treated with platinum + etoposide-based neoadjuvant chemotherapy and 5 were treated with initial radical surgery. Seven of the 9 patients had post-operative adjuvant therapy consisting of chemotherapy, chemo-radiation or radiation only. Seven of the 9 patients (78%) were alive at last follow-up. Of the two patients who were deceased, one had metastatic disease found at surgery and the other declined adjuvant therapy and died of recurrence. Patients with stage II-IV disease (n=15) had a median PFS and OS of 11.5 and 12.1 months, respectively. Only 2 had no evidence of disease at last encounter. The remainder died without achieving remission. Patients with metastatic disease had significantly worse survival when compared to those with loco-regional disease with a median OS of 8 vs. 28 months (p = .03), respectively. Conclusions: We report one of the largest single-institution experiences of neuroendocrine cervical cancer. Advanced-stage patients had a poor prognosis regardless of therapy. However, multi-modality therapy in early-stage disease resulted in an excellent prognosis (78% survival) for these rare, highly aggressive tumors. These findings support the goal of curative intent for early-stage disease using multi-modality therapy.

scholarly journals Surgery in Small-Cell Lung Cancer

Cancers ◽  
2021 ◽  
Vol 13 (3) ◽  
pp. 390
Author(s):  
Nicola Martucci ◽  
Alessandro Morabito ◽  
Antonello La Rocca ◽  
Giuseppe De Luca ◽  
Rossella De Cecio ◽  
...  
Keyword(s):  
Lung Cancer ◽  
Small Cell Lung Cancer ◽  
Cell Lung Cancer ◽  
Early Stage ◽  
Small Cell ◽  
Stage I ◽  
Phase Iii ◽  
Small Cell Lung ◽  
Early Stage Disease ◽  
Stage Disease

Small-cell lung cancer (SCLC) is one of the most aggressive tumors, with a rapid growth and early metastases. Approximately 5% of SCLC patients present with early-stage disease (T1,2 N0M0): these patients have a better prognosis, with a 5-year survival up to 50%. Two randomized phase III studies conducted in the 1960s and the 1980s reported negative results with surgery in SCLC patients with early-stage disease and, thereafter, surgery has been largely discouraged. Instead, several subsequent prospective studies have demonstrated the feasibility of a multimodality approach including surgery before or after chemotherapy and followed in most studies by thoracic radiotherapy, with a 5-year survival probability of 36–63% for patients with completely resected stage I SCLC. These results were substantially confirmed by retrospective studies and by large, population-based studies, conducted in the last 40 years, showing the benefit of surgery, particularly lobectomy, in selected patients with early-stage SCLC. On these bases, the International Guidelines recommend a surgical approach in selected stage I SCLC patients, after adequate staging: in these cases, lobectomy with mediastinal lymphadenectomy is considered the standard approach. In all cases, surgery can be offered only as part of a multimodal treatment, which includes chemotherapy with or without radiotherapy and after a proper multidisciplinary evaluation.

Gene Expression Profiles as Predictors of Poor Outcomes in Stage II Colorectal Cancer: A Systematic Review and Meta-analysis

2009 ◽  
Vol 8 (4) ◽  
pp. 207-214 ◽  
Author(s):  
An-Ting T. Lu ◽  
Shelley R. Salpeter ◽  
Anthony E. Reeve ◽  
Steven Eschrich ◽  
Patrick G. Johnston ◽  
...  
Keyword(s):  
Gene Expression ◽  
Colorectal Cancer ◽  
Systematic Review ◽  
Expression Profiles ◽  
Meta Analysis ◽  
Gene Expression Profiles ◽  
Stage Ii ◽  
Stage Ii Colorectal Cancer ◽  
Poor Outcomes

scholarly journals Impact of 70-Gene Signature Use on Adjuvant Chemotherapy Decisions in Patients With Estrogen Receptor–Positive Early Breast Cancer: Results of a Prospective Cohort Study

2017 ◽  
Vol 35 (24) ◽  
pp. 2814-2819 ◽  
Author(s):  
Anne Kuijer ◽  
Marieke Straver ◽  
Bianca den Dekker ◽  
Annelotte C.M. van Bommel ◽  
Sjoerd G. Elias ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Gene Expression ◽  
Estrogen Receptor ◽  
Early Stage ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Gene Signature ◽  
Early Stage Breast Cancer ◽  
Er Positive ◽  
Test Result

Purpose Gene-expression profiles increasingly are used in addition to conventional prognostic factors to guide adjuvant chemotherapy (CT) decisions. The Dutch guideline suggests use of validated gene-expression profiles in patients with estrogen receptor (ER) –positive, early-stage breast cancer without overt lymph node metastases. We aimed to assess the impact of a 70-gene signature (70-GS) test on CT decisions in patients with ER-positive, early-stage breast cancer. Patients and Methods In a prospective, observational, multicenter study in patients younger than 70 years old who had undergone surgery for ER-positive, early-stage breast cancer, physicians were asked whether they intended to administer adjuvant CT before deployment of the 70-GS test and after the test result was available. Results Between October 1, 2013, and December 31, 2015, 660 patients, treated in 33 hospitals, were enrolled. Fifty-one percent of patients had pT1cN0, BRII, HER2-Neu-negative breast cancer. On the basis of conventional clinicopathological characteristics, physicians recommended CT in 270 (41%) of the 660 patients and recommended withholding CT in 107 (16%) of the 660 patients. For the remaining 43% of patients, the physicians were unsure and unable to give advice before 70-GS testing. In patients for whom CT was initially recommended or not recommended, 56% and 59%, respectively, were assigned to a low-risk profile by the 70-GS (κ, 0.02; 95% CI, -0.08 to 0.11). After disclosure of the 70-GS test result, the preliminary advice was changed in 51% of patients who received a recommendation before testing; the definitive CT recommendation of the physician was in line with the 70-GS result in 96% of patients. Conclusion In this prospective, multicenter study in a selection of patients with ER-positive, early-stage breast cancer, 70-GS use changed the physician-intended recommendation to administer CT in half of the patients.

Gene Expression Profiles of Early Implant Adherent Cells in Smokers and Nonsmokers

2015 ◽  
Vol 41 (6) ◽  
pp. 640-645 ◽  
Author(s):  
Ghadeer Thalji ◽  
Lyndon F. Cooper ◽  
Salvador Nares
Keyword(s):  
Gene Expression ◽  
Early Stage ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Whole Genome ◽  
Adherent Cells ◽  
Mini Implants ◽  
Molecular Events ◽  
The Impact

The objective of this study was to evaluate the impact of smoking on the early molecular events involved in peri-implant healing at either a micro-roughened or a micro-roughened with superimposed nanofeatures surface implant in humans. Twenty-one subjects, 10 smokers and 11 nonsmokers received 4 mini-implants (2.2 × 5.0 mm; 2 of each surface). After 3 and 7 days, paired mini-implants were retrieved by reverse threading and RNA isolated from implant adherent cells. Whole genome microarrays were used interrogate the gene expression profiles. The study failed to identify differences in the gene expression profiles of implant adherent cells at this early stage of osseointegration (up to day 7) comparing smoker and nonsmoker individuals.

Response to PD-1 inhibition in early- and late-relapsing cutaneous melanoma.

2019 ◽  
Vol 37 (15_suppl) ◽  
pp. e21038-e21038
Author(s):  
Kelly Fitzgerald ◽  
Adil Daud
Keyword(s):  
Overall Response Rate ◽  
Response Rate ◽  
Early Stage ◽  
Stage I ◽  
Definitive Treatment ◽  
Early Stage Disease ◽  
Overall Response ◽  
Stage Disease ◽  
The Difference ◽  
Time To Relapse

e21038 Background: Up to 45% of stage I-II melanomas will relapse within 5 years, and some relapses occur more than 10 years after surgical resection. Little is known about the differences in tumor characteristics, including immunogenicity, of early- vs. late-relapsing melanoma, or the implication of these differences in response to PD-1 inhibition. Methods: A retrospective cohort study was conducted to compare time from definitive treatment of localized melanoma to relapse with response to pembrolizumab. Patients with prior stage I-II melanoma who relapsed, and then treated with pembrolizumab, were included in the study. Time to relapse was compared with overall response rate. Results: Among the study population, 66 patients initially presented with early stage disease that relapsed within the study period. The median time to relapse was 5 years (range 0.5-33 years, interquartile range 7.25, Q1 = 2, Q2 = 9.25). 9 patients (14%) relapsed within 2 years of surgery; these patients had a higher overall response rate to pembrolizumab than late-relapsing patients with marginal significance (88% vs 50%, p = 0.056). The difference became less significant when patients who relapsed before or after 5 years (70% vs 47%, respectively, p = 0.20), and before or after 10 years (64% vs 45%, p = .31). Conclusions: Patients with early-relapsing melanoma had higher ORR to pembrolizumab than patients with late-relapsing disease, with early relapse defined as earlier than 2 years from definitive surgical intervention. Late relapsing tumors may harbor mechanisms of resistance to immune checkpoint inhibition.

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