Pharmacogenetic profiling for oxaliplatin-based adjuvant chemotherapy (CT) benefit in stage II-III colon cancer (CC) patients: A GEMCAD study.

2012 ◽  
Vol 30 (15_suppl) ◽  
pp. 3618-3618
Author(s):  
Jaime Feliu ◽  
Ana Custodio ◽  
Juan Moreno ◽  
Jorge Aparicio ◽  
Javier Gallego ◽  
...  
Keyword(s):  
Early Stage ◽  
Disease Free Survival ◽  
Treatment Resistance ◽  
Stage Ii ◽  
Nucleotide Polymorphisms ◽  
Genotype Relative Risk ◽  
Prognostic Information ◽  
Combined Analysis ◽  
Risk Of Recurrence

3618 Background: Identifying molecular biomarkers for tumour recurrence is critical in successfully selecting early-stage CC patients who are more likely to benefit from adjuvant CT. We tested whether single nucleotide polymorphisms (SNP) within genes involved in biological pathways of interest for CC progression and treatment resistance would predict the risk of recurrence in stage II-III CC patients treated with oxaliplatin and fluoropyrimidines-based adjuvant CT. Methods: Genomic DNA was extracted from formalin-fixed paraffin-embedded samples from 202 surgically treated high-risk stage II (29.7%) and stage III (70.29%) CC patients receiving adjuvant CT (25.24% FOLFOX, 74.75% XELOX) from January 2004 to December 2008. Minimum follow-up was 36 months. Genotyping was performed for 62 SNPs in 31 genes using the MassARRAY (SEQUENOM) technology. Our results were validated in an independent cohort of 177 stage II-III CC. Results: After a median follow-up of 51.4 months (7-96), 63 patients (31.18%) had experienced a relapse and 31 (15.34%) had died. Three-year disease-free survival (DFS) and overall survival (OS) were 72.2% (+/-0.032) and 89.1% (+/-0.022), respectively. Multivariate analysis showed that the risk of recurrence for patients with the E-selectine rs3917412 G>A G/G genotype was higher than for those with any A allele genotype [relative risk (RR): 2.02, 95% confidence interval (CI): 1.09-3.73, p=0.024]. In haplotype analysis, patients harboring the E-selectine rs3917412 G>A G/G and methylentetrahydrofolate reductase (MTHFR) rs1801133 C>T T/T haplotype had a higher risk of developing tumor recurrence compared to the E-selectine rs3917412 G>A any A and/or MTHFR rs1801133 C>T any C haplotype (RR: 3.39, 95% CI, 1.51-7.62, p=0.003). The ability to predict recurrence of this combined analysis was independently validated in the second cohort (RR: 3.75, 95% CI, 1.32-10.68, p=0.013). Conclusions: E-selectine and MTHFR SNPs were found to be independent prognostic markers for stage II-III CC patients, suggesting that this combined analysis provides additional prognostic information to that offered by clinicopathologic variables.

Concomitant Radiotherapy and Chemotherapy for Early-Stage Nasopharyngeal Carcinoma

2000 ◽  
Vol 18 (10) ◽  
pp. 2040-2045 ◽  
Author(s):  
Skye Hongiun Cheng ◽  
Stella Y. C. Tsai ◽  
K. Lawrence Yen ◽  
James Jer-Min Jian ◽  
Nei-Min Chu ◽  
...  
Keyword(s):  
Early Stage ◽  
Disease Free Survival ◽  
Stage I ◽  
Stage Ii ◽  
Free Survival ◽  
Radiotherapy Group ◽  
Radiotherapy Alone ◽  
Disease Free ◽  
Concomitant Radiotherapy

PURPOSE: Early-stage nasopharyngeal carcinoma (NPC) continues to carry a failure rate of 15% to 30% when treated with radiotherapy alone; the benefit of concomitant radiotherapy and chemotherapy (CCRT) in early-stage NPC is unclear. The purpose of this report is to describe our efforts to improve treatment outcome in early-stage NPC after CCRT. PATIENTS AND METHODS: Of 189 newly diagnosed NPC patients without evidence of distant metastases who were treated in our institution between 1990 and 1997, 44 presented with early-stage (stage I and II) disease according to the American Joint Committee on Cancer (AJCC) 1997 NPC staging system. Twelve of these patients were treated with radiotherapy alone and 32 with CCRT. Each patient’s head and neck area was evaluated by magnetic resonance imaging or computed tomography. Radiotherapy was administered at 2 Gy per fraction per day, Monday through Friday, for 35 fractions for a total dose of 70 Gy. Chemotherapy consisting of cis-diamine-dichloroplatinum and fluorouracil was delivered simultaneously with radiotherapy in weeks 1 and 6 and sequentially for two monthly cycles after radiotherapy. RESULTS: Patients who were treated with radiotherapy alone primarily had stage I disease, whereas none of those who were treated with CCRT had stage I disease (11 of 12 patients v none of 32 patients; P = .001). The locoregional control rate at 3 years for the radiotherapy group was 91.7% (median follow-up period, 34 months) and was 100% for the CCRT group (median follow-up period, 44 months) (P = .10). The 3-year disease-free survival rate in the radiotherapy group was 91.7% and was 96.9% in the CCRT group (P = .66). CONCLUSION: Our results reveal excellent prognosis of AJCC 1997 stage II NPC treated with CCRT. Stage II patients with a greater tumor burden treated with CCRT showed an equal disease-free survival, compared with stage I patients treated with radiotherapy alone. A prospective randomized trial is underway to confirm the role of CCRT in stage II NPC.

scholarly journals Obesity and Risk of Recurrence or Death After Adjuvant Endocrine Therapy With Letrozole or Tamoxifen in the Breast International Group 1-98 Trial

2012 ◽  
Vol 30 (32) ◽  
pp. 3967-3975 ◽  
Author(s):  
Marianne Ewertz ◽  
Kathryn P. Gray ◽  
Meredith M. Regan ◽  
Bent Ejlertsen ◽  
Karen N. Price ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Early Stage ◽  
Disease Free Survival ◽  
Normal Weight ◽  
Baseline Body Mass Index ◽  
Risk Of Recurrence ◽  
Breast International Group ◽  
International Group ◽  
Free Interval

Purpose To examine the association of baseline body mass index (BMI) with the risk of recurrence or death in postmenopausal women with early-stage breast cancer receiving adjuvant tamoxifen or letrozole in the Breast International Group (BIG) 1-98 trial at 8.7 years of median follow-up. Patients and Methods This report analyzes 4,760 patients with breast cancer randomly assigned to 5 years of monotherapy with letrozole or tamoxifen in the BIG 1-98 trial with available information on BMI at randomization. Multivariable Cox modeling assessed the association of BMI with disease-free survival, overall survival (OS), breast cancer–free interval, and distant recurrence-free interval and tested for treatment-by-BMI interaction. Median follow-up was 8.7 years. Results Seventeen percent of patients have died. Obese patients (BMI ≥ 30 kg/m2) had slightly poorer OS (hazard ratio [HR] = 1.19; 95% CI, 0.99 to 1.44) than patients with normal BMI (< 25 kg/m2), whereas no trend in OS was observed in overweight (BMI 25 to < 30 kg/m2) versus normal-weight patients (HR = 1.02; 95% CI, 0.86 to 1.20). Treatment-by-BMI interactions were not statistically significant. The HRs for OS comparing obese versus normal BMI were HR = 1.22 (95% CI, 0.93 to 1.60) and HR = 1.18 (95% CI, 0.91 to 1.52) in the letrozole and tamoxifen groups, respectively. Conclusion There was no evidence that the benefit of letrozole over tamoxifen differed according to patients' BMI.

scholarly journals The role of functional polymorphisms in oxidative stress-related genes on early-stage breast cancer survival

2021 ◽  
pp. 172460082110111
Author(s):  
Erika Korobeinikova ◽  
Rasa Ugenskiene ◽  
Ruta Insodaite ◽  
Viktoras Rudzianskas ◽  
Jurgita Gudaitiene ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Overall Survival ◽  
Single Nucleotide Polymorphisms ◽  
Early Stage ◽  
Disease Free Survival ◽  
Early Stage Breast Cancer ◽  
Nucleotide Polymorphisms ◽  
Single Nucleotide ◽  
Free Survival ◽  
Disease Free

Background: Genetic variations in oxidative stress-related genes may alter the coded protein level and impact the pathogenesis of breast cancer. Methods: The current study investigated the associations of functional single nucleotide polymorphisms in the NFE2L2, HMOX1, P21, TXNRD2, and ATF3 genes with the early-stage breast cancer clinicopathological characteristics and disease-free survival, metastasis-free survival, and overall survival. A total of 202 Eastern European (Lithuanian) women with primary I–II stage breast cancer were involved. Genotyping of the single nucleotide polymorphisms was performed using TaqMan single nucleotide polymorphisms genotyping assays. Results: The CA+AA genotypes of P21 rs1801270 were significantly less frequent in patients with lymph node metastasis and larger tumor size ( P=0.041 and P=0.022, respectively). The TT genotype in ATF3 rs3125289 had significantly lower risk of estrogen receptor (ER), progesterone receptor (PR) negative, and human epidermal growth factor receptor 2 (HER2) positive status ( P=0.023, P=0.046, and P=0.040, respectively). In both, univariate and multivariate Cox analysis, TXNRD2 rs1139793 GG genotype vs. GA+AA was a negative prognostic factor for disease-free survival (multivariate hazard ratio (HR) 2.248; P=0.025) and overall survival (multivariate HR 2.248; P=0.029). The ATF3 rs11119982 CC genotype in the genotype model was a negative prognostic factor for disease-free survival (multivariate HR 5.878; P=0.006), metastasis-free survival (multivariate HR 4.759; P=0.018), and overall survival (multivariate HR 3.280; P=0.048). Conclusion: Our findings suggest that P21 rs1801270 is associated with lymph node metastasis and larger tumor size, and ATF3 rs3125289 is associated with ER, PR, and HER2 status. Two potential, novel, early-stage breast cancer survival biomarkers, TXNRD2 rs1139793 and ATF3 rs11119982, were detected. Further investigations are needed to confirm the results of the current study.

scholarly journals Targeted Plasma Metabolic Profiles and Risk of Recurrence in Stage II and III Colorectal Cancer Patients: Results from an International Cohort Consortium

Metabolites ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 129
Author(s):  
Jennifer Ose ◽  
Biljana Gigic ◽  
Stefanie Brezina ◽  
Tengda Lin ◽  
Andreas Baierl ◽  
...  
Keyword(s):  
Colorectal Cancer ◽  
Multiple Testing ◽  
Tumor Stage ◽  
Stage Ii ◽  
Sphingolipid Metabolism ◽  
Risk Of Recurrence ◽  
Cox Proportional Hazard Models ◽  
Edta Plasma ◽  
Colorectal Cancer Patients

The identification of patients at high-risk for colorectal cancer (CRC) recurrence remains an unmet clinical need. The aim of this study was to investigate associations of metabolites with risk of recurrence in stage II/III CRC patients. A targeted metabolomics assay (128 metabolites measured) was performed on pre-surgery collected EDTA plasma samples from n = 440 newly diagnosed stage II/III CRC patients. Patients have been recruited from four prospective cohort studies as part of an international consortium: Metabolomic profiles throughout the continuum of CRC (MetaboCCC). Cox proportional hazard models were computed to investigate associations of metabolites with recurrence, adjusted for age, sex, tumor stage, tumor site, body mass index, and cohort; false discovery rate (FDR) was used to account for multiple testing. Sixty-nine patients (15%) had a recurrence after a median follow-up time of 20 months. We identified 13 metabolites that were nominally associated with a reduced risk of recurrence. None of the associations were statistically significant after controlling for multiple testing. Pathway topology analyses did not reveal statistically significant associations between recurrence and alterations in metabolic pathways (e.g., sphingolipid metabolism p = 0.04; pFDR = 1.00). To conclude, we did not observe statistically significant associations between metabolites and CRC recurrence using a well-established metabolomics assay. The observed results require follow-up in larger studies.

Prevalence of EGFR mutation testing in early-stage lung cancer: Implications of the ADAURA trial for clinical practice.

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e20507-e20507
Author(s):  
Estelamari Rodriguez ◽  
Richa Dawar ◽  
Fahmin Basher ◽  
Philippos Apolinario Costa ◽  
Tisdrey Torres ◽  
...  
Keyword(s):  
Egfr Mutation ◽  
Early Stage ◽  
Disease Free Survival ◽  
Mutation Testing ◽  
Egfr Mutations ◽  
Early Stage Lung Cancer ◽  
Free Survival ◽  
Stage Ib ◽  
Egfr Mutation Testing

e20507 Background: It is reported that about 20% of patients with resected NSCLC adenocarcinoma harbor an EGFR driver mutation in the United States. Up to the recent approval of osimertinib in the adjuvant setting for resected EGFR + NSCLC based on the ADAURA trial, routine molecular profiling of early-stage lung cancer had not been standard of care. We hypothesize that there is a significant proportion of patients with resected adenocarcinoma with unknown EGFR status who could benefit from treatment that are missed with our current testing practices. Methods: We performed a retrospective analysis of Stage IB-IIIA lung adenocarcinomas resected at the University of Miami from 2014 to 2019. Eligible patients were identified from the Cancer Registry and information on EGFR mutation testing and treatment was obtained from chart review. We evaluated the prevalence of EGFR mutation testing in this population and outcomes based on EGFR mutation status. Disease free survival (DFS) and clinico-pathologic characteristics were evaluated. We estimated the number of patients that would have been eligible for EGFR testing and adjuvant osimertinib therapy in the pre-ADAURA era in our patient cohort. Results: A total of 120 patients had resected stage IB-IIIA adenocarcinoma during this five-year period (Stage IB 42.5%; Stage IIA 13.3%; Stage IIB 25%; Stage IIIA 19.2%) with a median age of 66 years. Most were females (59%), NHWs (51.5%), Hispanics (46.9%), and former smokers (66.7%). Out of patients with Stage IB-IIIA NSCLC with adenocarcinoma, 42.5% completed recommended adjuvant platinum-based chemotherapy. Only 40% of patients were referred for EGFR testing during this study period. The prevalence of EGFR mutations in this population was 10.8% (13 /120), but 59% of cases had no available EGFR testing. The most prevalent mutation was L858R (53.8%) followed by exon-19 deletions (30.8%). A total of 6 patients received an EGFR TKI therapy during the follow up period (2 in the adjuvant setting). With a median follow up of 12 mos, the rate of recurrence by stage was: Stage IB (3.9%); Stage IIB (10%); Stage IIIA (13%). Median time to disease progression or death was 13 months in this subgroup. There was no difference in disease free survival for patients with EGFR testing and those without results available in this short follow up period. Conclusions: Based on this retrospective review, up to 60% of patients with early-stage NSCLC with non-squamous histology have no available EGFR testing in the pre-ADAURA era. Of the anticipated 20% of patients with expected EGFR mutations based on historical controls, we have only identified half of patients that would have been eligible for adjuvant osimertinib. This study establishes the importance of upfront EGFR mutation testing in all NSCLC patients, not only to prognosticate, but also to identify the subset of patients who could benefit from adjuvant EGFR therapy.

scholarly journals Assessing the Clinical Benefit of Systemic Adjuvant Therapies for Early Breast Cancer

2017 ◽  
Vol 77 (10) ◽  
pp. 1079-1087 ◽  
Author(s):  
Volker Möbus ◽  
Susanne Hell ◽  
Marcus Schmidt
Keyword(s):  
Breast Cancer ◽  
Early Breast Cancer ◽  
Clinical Benefit ◽  
Early Stage ◽  
Survival Rates ◽  
Disease Free Survival ◽  
New Drugs ◽  
Early Stage Breast Cancer ◽  
Risk Of Recurrence ◽  
Adjuvant Therapies

AbstractOncologic therapy is currently undergoing significant changes. A number of innovative targeted medications currently in clinical development have raised high expectations. With that in mind, discussions about terms such as “clinical benefit” and “clinical relevance” are highly topical. This also applies to further developments in the field of adjuvant systemic therapies for early-stage breast cancer. As the treatment aim is curative, assessment of the clinical benefit of adjuvant therapies must be largely based on efficacy outcomes. The focus must be on improving disease-free survival rates and lowering the risk of recurrence. Because of the current low mortality rates, statements about overall survival rates are only possible after very long observation periods. Consequently, new drugs in adjuvant therapies should be considered as offering a clinical benefit, if they reduce the risk of recurrence below current low levels of risk. The evidence for established adjuvant therapy standards in early-stage breast cancer can be used as objective criteria for comparison. This review article considers the requirements for clinical benefit of new adjuvant therapies for early breast cancer, based on examples from adjuvant endocrine therapy, adjuvant polychemotherapy and adjuvant anti-HER2 therapy.

scholarly journals A mid-term follow-up of Koutsogiannis’ osteotomy in adult-acquired flatfoot stage II and “early stage III”

SICOT-J ◽  
2017 ◽  
Vol 3 ◽  
pp. 24
Author(s):  
Camilla Arvinius ◽  
Elena Manrique ◽  
Antonio Urda ◽  
Zulema Cardoso ◽  
Jose Enrique Galeote ◽  
...  
Keyword(s):  
Early Stage ◽  
Stage Ii ◽  
Stage Iii

Second Primary Melanomas: Incidence and Outcome

2010 ◽  
Vol 76 (7) ◽  
pp. 675-681 ◽  
Author(s):  
Matthew R. Bower ◽  
Charles R. Scoggins ◽  
Robert C. G. Martin ◽  
Michael P. Mays ◽  
Michael J. Edwards ◽  
...  
Keyword(s):  
Early Stage ◽  
Primary Melanoma ◽  
Disease Free Survival ◽  
Second Primary ◽  
Free Survival ◽  
Kaplan Meier ◽  
Ongoing Surveillance ◽  
Post Hoc ◽  
Disease Free

The objective of this study was to determine the incidence of multiple primary melanomas (MPM) and other cancers types among patients with melanoma. Factors associated with development of MPM were assessed in a post hoc analysis of the database from a multi-institutional prospective randomized trial of patients with melanoma aged 18 to 70 years with Breslow thickness 1 mm or greater. Disease-free survival (DFS) and overall survival (OS) were evaluated by Kaplan-Meier analysis. Forty-eight (1.9%) of 2506 patients with melanoma developed additional primary melanomas. Median follow-up was 66 months. Except in one patient, the subsequent melanomas were thinner (median, 0.32 mm vs 1.50 mm; P < 0.0001). Compared with patients without MPM, patients with MPM were more likely to be older (median age, 54.5 vs 51.0 years; P = 0.048), to have superficially spreading melanomas (SSM) ( P = 0.025), to have negative sentinel lymph nodes ( P = 0.021), or to lack lymphovascular invasion (LVI) ( P = 0.008) with the initial tumor. On multivariate analysis, age ( P = 0.028), LVI ( P = 0.010), and SSM subtype of the original melanoma ( P = 0.024) were associated with MPM. Patients with MPM and patients with single primary melanoma had similar DFS (5-year DFS 88.7 vs 81.3%, P = 0.380), but patients with MPM had better OS (5-year OS 95.3 vs 80.0%, P = 0.005). Nonmelanoma malignancies occurred in 152 patients (6.1%). Ongoing surveillance of patients with melanoma is important given that a significant number will develop additional melanoma and nonmelanoma tumors. With close follow-up, second primary melanomas are usually detected at an early stage.

Adjuvant therapy with alpha-interferon in radically resected stage Il and III renal cell carcinoma

1992 ◽  
Vol 59 (1_suppl) ◽  
pp. 160-162
Author(s):  
◽  
Urologico Lombardo
Keyword(s):  
Renal Cell Carcinoma ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Randomized Study ◽  
Disease Free Survival ◽  
Stage Ii ◽  
Alpha Interferon ◽  
Free Survival ◽  
Resected Stage

In February 1990, a multicentric randomized study was started to verify the therapeutic efficacy of adjuvant alpha-interferon in Robson's stage II and III renal cell carcinoma. Up to April 1992, 749 radical nephrectomies have been recorded by the 25 participating centers. Stage II and III patients fullfilling selection criteria were 124: 64 were assigned to Interferon therapy and 60 to control. The short follow-up does not allow any evaluation of the relapse rate. Therapy related toxicity was represented by mild fever and flu-like syndrome in 50% of cases and slight leucopenia in 5%. The recruitment of the first 200 randomized patients will end approximately within 1 year. While evaluating the hypothesis of a 20% difference in the 5 year disease-free survival between the two groups recruitment will continue up to a total of 350 cases, in order to verify the 15% hypothesis, too.

scholarly journals Tumor-Infiltrating Lymphocytes and Prognosis: A Pooled Individual Patient Analysis of Early-Stage Triple-Negative Breast Cancers

2019 ◽  
Vol 37 (7) ◽  
pp. 559-569 ◽  
Author(s):  
Sherene Loi ◽  
Damien Drubay ◽  
Sylvia Adams ◽  
Giancarlo Pruneri ◽  
Prudence A. Francis ◽  
...  
Keyword(s):  
Triple Negative ◽  
Early Stage ◽  
Disease Free Survival ◽  
Tumor Infiltrating Lymphocytes ◽  
Cox Proportional Hazards ◽  
Prognostic Information ◽  
Free Survival ◽  
Node Negative ◽  
Infiltrating Lymphocytes ◽  
Disease Free

Purpose The aim of the current study was to conduct a pooled analysis of studies that have investigated the prognostic value of tumor-infiltrating lymphocytes (TILs) in early-stage triple negative breast cancer (TNBC). Methods Participating studies had evaluated the percentage infiltration of stromally located TILs (sTILs) that were quantified in the same manner in patient diagnostic samples of early-stage TNBC treated with anthracycline-based chemotherapy with or without taxanes. Cox proportional hazards regression models stratified by trial were used for invasive disease-free survival (iDFS; primary end point), distant disease-free survival (D-DFS), and overall survival (OS), fitting sTILs as a continuous variable adjusted for clinicopathologic factors. Results We collected individual data from 2,148 patients from nine studies. Average age was 50 years (range, 22 to 85 years), and 33% of patients were node negative. The average value of sTILs was 23% (standard deviation, 20%), and 77% of patients had 1% or more sTILs. sTILs were significantly lower with older age ( P = .001), larger tumor size ( P = .01), more nodal involvement ( P = .02), and lower histologic grade ( P = .001). A total of 736 iDFS and 548 D-DFS events and 533 deaths were observed. In the multivariable model, sTILs added significant independent prognostic information for all end points (likelihood ratio χ2, 48.9 iDFS; P < .001; χ2, 55.8 D-DFS; P < .001; χ2, 48.5 OS; P < .001). Each 10% increment in sTILs corresponded to an iDFS hazard ratio of 0.87 (95% CI, 0.83 to 0.91) for iDFS, 0.83 (95% CI, 0.79 to 0.88) for D-DFS, and 0.84 (95% CI, 0.79 to 0.89) for OS. In node-negative patients with sTILs ≥ 30%, 3-year iDFS was 92% (95% CI, 89% to 98%), D-DFS was 97% (95% CI, 95% to 99%), and OS was 99% (95% CI, 97% to 100%). Conclusion This pooled data analysis confirms the strong prognostic role of sTILs in early-stage TNBC and excellent survival of patients with high sTILs after adjuvant chemotherapy and supports the integration of sTILs in a clinicopathologic prognostic model for patients with TNBC. This model can be found at www.tilsinbreastcancer.org .

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