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Dynamic recurrence risk and adjuvant chemotherapy benefit prediction by ctDNA in resected NSCLC.

ABSTRACT: Accurately evaluating minimal residual disease (MRD) could facilitate early intervention and personalized adjuvant therapies. Here, using ultradeep targeted next-generation sequencing (NGS), we evaluate the clinical utility of circulating tumor DNA (ctDNA) for dynamic recurrence risk and adjuvant chemotherapy (ACT) benefit prediction in resected non-small cell lung cancer (NSCLC). Both postsurgical and post-ACT ctDNA positivity are significantly associated with worse recurrence-free survival. In stage II-III patients, the postsurgical ctDNA positive group benefit from ACT, while ctDNA negative patients have a low risk of relapse regardless of whether or not ACT is administered. During disease surveillance, ctDNA positivity precedes radiological recurrence by a median of 88 days. Using joint modeling of longitudinal ctDNA analysis and time-to-recurrence, we accurately predict patients' postsurgical 12-month and 15-month recurrence status. Our findings reveal longitudinal ctDNA analysis as a promising tool to detect MRD in NSCLC, and we show pioneering work of using postsurgical ctDNA status to guide ACT and applying joint modeling to dynamically predict recurrence risk, although the results need to be further confirmed in future studies.

SUBMITTER: Qiu B

PROVIDER: S-EPMC8605017 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Prognostic value of ESR2 expression on adjuvant chemotherapy in completely resected NSCLC.

Project description:BackgroundPrognostic biomarker, which can inform the treatment outcome of adjuvant chemotherapy (ACT) after complete resection of early-stage non-small cell lung cancer (NSCLC), is urgently needed for the personalized treatment of these patients.Patients and methodsThe prognostic value of gene expression of the estrogen receptor (ER) on the effect of ACT in completely resected NSCLC was investigated in the present study. Two independent datasets from Gene Expression Omnibus (GEO) with a total of 309 patients were included in this study. The prognostic value of ER gene expression on ACT's efficacy was evaluated by survival analysis and Cox hazards models.ResultsWe found a consistent and significant prognostic value of ERβ (ESR2) expression for ACT's efficacy in completely resected NSCLC in both of the two independent cohorts. After multivariate adjustment, a significant survival benefit of ACT was observed in patients with low expression of ESR2, with a hazard ratio (HR) of 0.19 (95%CI 0.05-0.82, p = 0.026) in the discovery cohort and an HR of 0.27 (95%CI 0.10-0.76, p = 0.012) in the validation group. No significant benefit of ACT in the subgroup of patients with high expression of ESR2 was observed, with an HR of 0.80 (95%CI 0.31-2.09, p = 0.644) in the discovery cohort and an HR of 1.05 (95%CI 0.48-2.29, p = 0.896) in the validation group.ConclusionA significant survival benefit from ACT was observed in patients with low ESR2 expression. No significant survival benefit was observed in patients with high ESR2 expression. Detection of ESR2 expression in NSCLC may help personalize its treatment after complete resection.

| S-EPMC7746143 | biostudies-literature

Adjuvant chemotherapy of completely resected early stage non-small cell lung cancer (NSCLC).

Project description:Surgery is regarded as the primary treatment modality for early stage non-small cell lung cancer (NSCLC), but even after complete resection, a substantial percentage of these patients eventually develop local recurrence or distant metastases. Therefore more effective treatment strategies to reduce lung cancer mortality and recurrence rate are needed. Only recently has the use of adjuvant chemotherapy become standard in early stage NSCLC, at least for stage II and resected IIIA NSCLC. Controversies remain about the benefit for stage I patients. Five-year survival improvements of 5% to 10% have been reported with cisplatin-based adjuvant chemotherapy from multiple large randomized phase III clinical trials and meta-analyses. Questions remain as to which patients benefit and which regimens are best. In this paper, important clinical research in the field of adjuvant chemotherapy of NSCLC is reviewed.

| S-EPMC4367729 | biostudies-literature

Benefit of Adjuvant Chemoradiotherapy in Resected Gallbladder Carcinoma.

Project description:To evaluate the benefit of adjuvant treatments, such as chemoradiotherapy (CRT) and chemotherapy (CTx), compared with no adjuvant treatment (No-AT) in resected gallbladder (GB) cancer patients, 151 patients were analyzed: 98 (64.9%) patients received adjuvant treatment with CRT (n?=?59, 39.1%) or CTx (n?=?39, 25.8%), and the remaining 53 (35.1%) did not (No-AT). The clinicopathological factors, patterns of failure, locoregional recurrence-free survival (LRFS), recurrence-free survival (RFS) and overall survival (OS) were compared among the three groups according to tumor stage. In patients with T2-3N0M0 stage disease, the incidences of locoregional recurrence and distant recurrence and 5-year LRFS, RFS and OS rates were not significantly different among the No-AT, CTx, and CRT groups (p?>?0.05 each). In those with T2-3N1-2M0 stage disease, the incidences of locoregional recurrence (11.4%, 78.1%, and 68.4%, respectively) and distant recurrence (42.8%, 73.9% and 66.7%, respectively) in the CRT group were significantly lower than those in the No-AT and CTx groups (p?<?0.05), and the CRT group had significantly higher 5-year LRFS (82,1%, 26.8%, and 19.0%), RFS (53.3%, 11.6% and 16.7%) and OS rates (64.0%, 22.7% and 4.3%) than the CTx and No-AT groups (p?<?0.05 each). Therefore, adjuvant CRT may improve the LRFS and RFS and subsequently improve OS in lymph node-positive resected GB cancer.

| S-EPMC6692378 | biostudies-literature

Update on adjuvant therapy in completely resected NSCLC patients.

Project description:In patients with completely resected non-small cell lung cancer (NSCLC), postoperative adjuvant chemotherapy has been associated with improvement in survival by minimizing the risk of recurrence. For years, systemic chemotherapy including platinum based regimen has been a mainstay treatment modality of adjuvant treatment after complete resection. ADAURA study showed that among completely resected IB to IIIA NSCLC, disease-free survival was significantly better in patients under adjuvant osimertinib than a placebo group. After the advent of a variety of new treatment regimens, such as third generation TKI and immunotherapy, the landscape of postoperative adjuvant treatment has been changing. In this review, we discuss some key issues regarding choice of adjuvant treatment after complete resection in NSCLC, and provide further updates on recent advances in treatment modalities.

| S-EPMC8807337 | biostudies-literature

Benefit of adjuvant chemotherapy on recurrence free survival per consensus molecular subtype in stage III colon cancer

Project description:In this study, we evaluated the added value of CMS in predicting both prognosis and benefit of adjuvant chemotherapy in stage III CC patients.

2024-07-10 | GSE250057 | GEO

Adjuvant or neoadjuvant chemotherapy for NSCLC.

Project description:In functionally fit patients with localized disease surgical resection remains the treatment of choice. There is also good evidence to support the use of chemotherapy in stages II-III. However, whether to use neoadjuvant or adjuvant therapy has been the topic of much debate. With its strong evidence base, adjuvant chemotherapy has been adopted in the European Society of Medical Oncology clinical practice guidelines for early and locally advanced stages II-III non-small-cell lung cancer (NSCLC), with consideration of adjuvant therapy in those with stage IB but with tumours >4 cm in size. There are fewer trials comparing neoadjuvant therapy plus surgery with surgery alone. Even less has been carried out directly comparing neoadjuvant with adjuvant therapy. The NATCH trial demonstrated no difference in survival between adjuvant and neoadjuvant arms, whilst others have yet to be completed. Meta-analysis also demonstrates no appreciable difference between the two methods. With such a strong body of evidence, however, postoperative delivery of chemotherapy remains the timing of choice in NSCLC.

| S-EPMC4032958 | biostudies-literature

High-risk endometrial cancer may be benefit from adjuvant radiotherapy plus chemotherapy.

Project description:To present patterns of practice and outcomes in the adjuvant treatment of intermediate- and high-risk endometrial cancer.Retrospective data on 224 women with intermediate-risk and high-risk endometrial cancer from 1999 to 2006 were reviewed. All patients underwent surgical staging. Patterns of adjuvant treatment, consisting of pelvic radiotherapy, chemotherapy, and radiotherapy plus chemotherapy, were assessed. The 3- and 5-year disease-specific survival (DSS) rates were calculated using the Kaplan-Meier method.The difference in 5-year DSS rate was statistically significant between adjuvant group and non-adjuvant group (80.65% vs. 63.80%, P=0.040). In 110 high-risk patients who underwent adjuvant treatment, both 5-year DSS rate and recurrent rate were significantly different in combined radiotherapy and chemotherapy group compared with radiotherapy alone and chemotherapy alone groups (DSS rate, P=0.049; recurrent rate, P=0.047). In 83 intermediate-risk women who underwent adjuvant treatment, there was no significant difference in 5-year DSS rate and recurrence rate among the combined radiotherapy and chemotherapy, radiotherapy alone and chemotherapy alone groups (DSS rate, P=0.776; recurrent rate, P=0.937).Adjuvant radiotherapy plus chemotherapy is associated with a higher 5-year DSS rate and lower recurrence rate compared with radiotherapy alone and chemotherapy alone in high-risk endometrial cancer patients. Patients with intermediate-risk endometrial cancer may be not likely to benefit from adjuvant combined radiotherapy and chemotherapy.

| S-EPMC3551334 | biostudies-other

Prediction of late disease recurrence and extended adjuvant letrozole benefit by the HOXB13/IL17BR biomarker.

Project description:BackgroundBiomarkers to optimize extended adjuvant endocrine therapy for women with estrogen receptor (ER)-positive breast cancer are limited. The HOXB13/IL17BR (H/I) biomarker predicts recurrence risk in ER-positive, lymph node-negative breast cancer patients. H/I was evaluated in MA.17 trial for prognostic performance for late recurrence and treatment benefit from extended adjuvant letrozole.MethodsA prospective-retrospective, nested case-control design of 83 recurrences matched to 166 nonrecurrences from letrozole- and placebo-treated patients within MA.17 was conducted. Expression of H/I within primary tumors was determined by reverse-transcription polymerase chain reaction with a prespecified cutpoint. The predictive ability of H/I for ascertaining benefit from letrozole was determined using multivariable conditional logistic regression including standard clinicopathological factors as covariates. All statistical tests were two-sided.ResultsHigh H/I was statistically significantly associated with a decrease in late recurrence in patients receiving extended letrozole therapy (odds ratio [OR] = 0.35; 95% confidence interval [CI] = 0.16 to 0.75; P = .007). In an adjusted model with standard clinicopathological factors, high H/I remained statistically significantly associated with patient benefit from letrozole (OR = 0.33; 95% CI = 0.15 to 0.73; P = .006). Reduction in the absolute risk of recurrence at 5 years was 16.5% for patients with high H/I (P = .007). The interaction between H/I and letrozole treatment was statistically significant (P = .03).ConclusionsIn the absence of extended letrozole therapy, high H/I identifies a subgroup of ER-positive patients disease-free after 5 years of tamoxifen who are at risk for late recurrence. When extended endocrine therapy with letrozole is prescribed, high H/I predicts benefit from therapy and a decreased probability of late disease recurrence.

| S-EPMC3888138 | biostudies-literature

A predictive model for identifying candidates for adjuvant chemotherapy based on recurrence risk profile of resected, node-negative (N0) non-small cell lung cancer.

Project description:BackgroundThe decision for administering adjuvant chemotherapy (AC) in completely resected node-negative non-small cell lung cancer (NSCLC) is guided by likelihood of disease recurrence or death based on tumor, node, metastasis (TNM) stage. However, within each TNM stage are sub-groups of patients that are more or less likely to relapse than stage alone predicts.MethodsIn this retrospective cohort study, prospective data from 394 consecutive patients who underwent complete resection of node-negative NSCLC without adjuvant therapies, between 2002 and 2019 was retrospectively analyzed. Independent tumor and host risk factors for recurrence were subjected to multivariate analysis to develop a predictive risk model distributing patients into low-risk or high-risk categories.ResultsRecurrence risk was independently predicted by a neutrophil:lymphocyte ratio (NLR) of ≥3.5 [hazard ratio (HR), 1.9; 95% confidence interval (CI), 1.1-3.5], visceral pleural invasion (HR, 2.2; 95% CI, 1.3-3.8), histopathology other than adenocarcinoma or squamous cell (HR, 2.6; 95% CI, 1.2-5.5) and tumor size >33 mm (HR, 3.9; 95% CI, 2.3-6.7). The specific combination of risk factors contributed to a score for a risk model which classified 9% of Stage I and 69% of Stage ≥II patients as high-risk. The predicted 5-year disease-free survival (DFS) for high-risk and low-risk patients as scored by the predictive model was 30% and 85%, respectively.ConclusionsOur readily reproducible, low-technology model, developed from individually validated tumor/host risk factors, identified sub-groups of resected node-negative NSCLC patients at significantly discordant risk of recurrence to their TNM stage category.

| S-EPMC7867833 | biostudies-literature

21-Gene Recurrence Score for prognosis and prediction of taxane benefit after adjuvant chemotherapy plus endocrine therapy: results from NSABP B-28/NRG Oncology.

Project description:BACKGROUND:The 21-gene recurrence score (RS) predicts outcome and benefit from adjuvant chemotherapy benefit in breast cancer patients treated with adjuvant endocrine therapy. In the NSABP B-28 study, we evaluated the 21-gene RS for its prognostic impact and its ability to predict benefit from paclitaxel (P) in node-positive, estrogen receptor-positive (ER+) breast cancer patients treated with adjuvant chemotherapy plus tamoxifen. METHODS:The B-28 trial compared doxorubicin/cyclophosphamide (AC) with AC followed by P in 3060 patients. Tamoxifen for 5 years was also given to patients > 50 years and those < 50 years with ER+ and/or progesterone receptor-positive (PR+) tumors. The present study includes 1065 ER-positive, tamoxifen-treated patients with RS assessment. Median follow-up time was 11.2 years. RESULTS:In univariate analyses, RS was a significant predictor of outcome. In multivariate analyses, RS remained a significant independent predictor of outcome beyond clinico-pathologic factors, age, and type of surgery (p < 0.001). In the study population (n = 1065), the disease-free survival (DFS) hazard ratio (HR) with adding P to AC was 0.87 (95% CI 0.72-1.05; p = 0.14). RS was not a significant predictor of P benefit: for DFS, HRs for adding P to AC in RS low, intermediate, and high subgroups were 1.01 (95% CI 0.69-1.47; p = 0.99), 0.84 (95% CI 0.62-1.14; p = 0.26), and 0.81 (95% CI 0.60-1.10; p = 0.21), respectively (interaction p = 0.64). Similar findings were observed for the other study endpoints. CONCLUSIONS:RS maintains significant prognostic impact in ER-positive, node-positive patients treated with adjuvant chemotherapy plus tamoxifen. However, RS did not significantly predict benefit from adding paclitaxel to AC chemotherapy. (Trial Registration: PDQ: NSABP-B-28).

| S-EPMC5996978 | biostudies-literature

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