The not so small role of adjuvant chemotherapy in resected non-small cell lung cancer.
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ABSTRACT:
SUBMITTER: Almquist DR
PROVIDER: S-EPMC8332728 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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
Project description:Most long-term survivors of non-small-cell lung cancer (NSCLC) are patients who have had a completely resected tumour. However, this is only achievable in about 30% of the patients. Even in this highly selected group of patients, there is still a high risk of both local and distant failure. Adjuvant treatments such as chemotherapy (CT) and radiotherapy (RT) have therefore been evaluated in order to improve their outcome. In patients with stage II and III, administration of adjuvant platinum-based chemotherapy is now considered the standard of care, based on level 1 evidence. The role of postoperative radiation therapy (PORT) remains controversial. In the PORT meta-analysis published in 1998, the conclusions were that if PORT was detrimental to patients with stage I and II completely resected NSCLC, the role of PORT in the treatment of tumours with N2 involvement was unclear and further research was warranted. Thus at present, after complete resection, adjuvant radiotherapy should not be administered in patients with early lung cancer. Recent retrospective and non-randomised studies, as well as subgroup analyses of recent randomised trials evaluating adjuvant chemotherapy, provide evidence of the possible benefit of PORT in patients with mediastinal nodal involvement. The role of PORT needs to be evaluated also for patients with proven N2 disease who undergo neoadjuvant chemotherapy followed by surgery. The risk of local recurrence for N2 patients varies between 20% and 60%. Based on currently available data, PORT should be discussed for fit patients with completely resected NSCLC with N2 nodal involvement, preferably after completion of adjuvant chemotherapy or after surgery if patients have had preoperative chemotherapy. There is a need for new randomised evidence to reassess PORT using modern three-dimensional conformal radiation technique, with attention to normal organ sparing, particularly lung and heart, to reduce the possible over-added toxicity. Quality assurance of radiotherapy as well as quality of surgery - and most particularly nodal exploration modality - should both be monitored. A new large multi-institutional randomised trial Lung ART evaluating PORT in this patient population is needed and is now under way.
| S-EPMC4041407 | biostudies-literature
Project description:Adjuvant chemotherapy for non-small-cell lung carcinoma (NSCLC) is a debated issue in clinical oncology. Although it is considered a standard for resected stage II-IIIA patients according to the available guidelines, many questions are still open. Among them, it should be acknowledged that the treatment for stage IB disease has shown so far a limited (if sizable) efficacy, the role of modern radiotherapies requires to be evaluated in large prospective randomized trials and the relative impact of age and comorbidities should be weighted to assess the reliability of the trials' evidences in the context of the everyday-practice. In addition, a conclusive evidence of the best partner for cisplatin is currently awaited as well as a deeper investigation of the fading effect of chemotherapy over time. The limited survival benefit since first studies were published and the lack of reliable prognostic and predictive factors beyond pathological stage, strongly call for the identification of bio-molecular markers and classifiers to identify which patients should be treated and which drugs should be used. Given the disappointing results of targeted therapy in this setting have obscured the initial promising perspectives, a biomarker-selection approach may represent the basis of future trials exploring adjuvant treatment for resected NSCLC.
| S-EPMC3284429 | biostudies-other
Project description:Background: The JBR.10 trial demonstrated significant survival benefit from adjuvant cisplatin/vinorelbine (ACT) in stage IB-II NSCLC (HR 0.69, p=0.04), but stage IB patients did not derive significant benefit (HR: 0.94, p= 0.79). We hypothesized that expression profiling could identify stage-independent subgroups of patients who might benefit from adjuvant chemotherapy. Methods: Gene expression profiling was conducted on mRNA isolated from frozen JBR.10 tumor samples (either from patients under observation [OBS], or treated with ACT). The minimum gene set that selected for the greatest separation of good and poor prognosis patient subgroups in OBS patients was identified and this gene signature was used to classify patients into high and low risk for death after surgery, and predict ACT effect. The prognostic gene signature was additionally tested on ACT patients and publicly available microarray datasets. Results: A 15-gene signature separated OBS patients into equal high and low risk subgroups with significantly different prognoses (HR 15.02, 95% CI 5.12-44.04, p=0.0001). The signature was prognostic in both stage IB and II. It was also predictive of improved survival following ACT treatment in high-risk patients (HR 0.33, 95% CI 0.17-0.63, p=0.0005), but not in low risk patients (HR 3.67, 95% CI 1.22-11.06, p=0.0133; interaction p=0.0001). The prognostic effect of the signature was validated in two independent gene expression datasets of 169 stage I-II adenocarcinoma and 106 squamous cell carcinoma patients. Conclusions: This microarray-based 15-gene prognostic expression signature is stage and histology independent and may select early stage NSCLC patients who are most likely to benefit from adjuvant chemotherapy with cisplatin/vinorelbine. Keywords: Expression profiling by microarray; prognosis prediction 90 samples
| S-ECPF-GEOD-14814 | biostudies-other
Project description:PurposeThe JBR.10 trial demonstrated benefit from adjuvant cisplatin/vinorelbine (ACT) in early-stage non-small-cell lung cancer (NSCLC). We hypothesized that expression profiling may identify stage-independent subgroups who might benefit from ACT.Patients and methodsGene expression profiling was conducted on mRNA from 133 frozen JBR.10 tumor samples (62 observation [OBS], 71 ACT). The minimum gene set that was selected for the greatest separation of good and poor prognosis patient subgroups in OBS patients was identified. The prognostic value of this gene signature was tested in four independent published microarray data sets and by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR).ResultsA 15-gene signature separated OBS patients into high-risk and low-risk subgroups with significantly different survival (hazard ratio [HR], 15.02; 95% CI, 5.12 to 44.04; P < .001; stage I HR, 13.31; P < .001; stage II HR, 13.47; P < .001). The prognostic effect was verified in the same 62 OBS patients where gene expression was assessed by qPCR. Furthermore, it was validated consistently in four separate microarray data sets (total 356 stage IB to II patients without adjuvant treatment) and additional JBR.10 OBS patients by qPCR (n = 19). The signature was also predictive of improved survival after ACT in JBR.10 high-risk patients (HR, 0.33; 95% CI, 0.17 to 0.63; P = .0005), but not in low-risk patients (HR, 3.67; 95% CI, 1.22 to 11.06; P = .0133; interaction P < .001). Significant interaction between risk groups and ACT was verified by qPCR.ConclusionThis 15-gene expression signature is an independent prognostic marker in early-stage, completely resected NSCLC, and to our knowledge, is the first signature that has demonstrated the potential to select patients with stage IB to II NSCLC most likely to benefit from adjuvant chemotherapy with cisplatin/vinorelbine.
| S-EPMC2988634 | biostudies-literature
Project description:Background: The JBR.10 trial demonstrated significant survival benefit from adjuvant cisplatin/vinorelbine (ACT) in stage IB-II NSCLC (HR 0.69, p=0.04), but stage IB patients did not derive significant benefit (HR: 0.94, p= 0.79). We hypothesized that expression profiling could identify stage-independent subgroups of patients who might benefit from adjuvant chemotherapy. Methods: Gene expression profiling was conducted on mRNA isolated from frozen JBR.10 tumor samples (either from patients under observation [OBS], or treated with ACT). The minimum gene set that selected for the greatest separation of good and poor prognosis patient subgroups in OBS patients was identified and this gene signature was used to classify patients into high and low risk for death after surgery, and predict ACT effect. The prognostic gene signature was additionally tested on ACT patients and publicly available microarray datasets. Results: A 15-gene signature separated OBS patients into equal high and low risk subgroups with significantly different prognoses (HR 15.02, 95% CI 5.12-44.04, p=0.0001). The signature was prognostic in both stage IB and II. It was also predictive of improved survival following ACT treatment in high-risk patients (HR 0.33, 95% CI 0.17-0.63, p=0.0005), but not in low risk patients (HR 3.67, 95% CI 1.22-11.06, p=0.0133; interaction p=0.0001). The prognostic effect of the signature was validated in two independent gene expression datasets of 169 stage I-II adenocarcinoma and 106 squamous cell carcinoma patients. Conclusions: This microarray-based 15-gene prognostic expression signature is stage and histology independent and may select early stage NSCLC patients who are most likely to benefit from adjuvant chemotherapy with cisplatin/vinorelbine. Keywords: Expression profiling by microarray; prognosis prediction 90 samples
2010-09-09 | E-GEOD-14814 | biostudies-arrayexpress
Project description:We evaluated the therapeutic usefulness of adjuvant chemotherapy in patients with completely resected non-small cell lung cancer (NSCLC). We also examined the relation between DNA ploidy pattern and the response to chemotherapy. A total of 267 patients with NSCLC (pathologically documented stage I, II, or IIIA) underwent complete resection, and DNA ploidy pattern was analysed. Patients with stage I disease (n=172) were randomly assigned to receive surgery alone (group A) or surgery followed by adjuvant chemotherapy (UFT (oral anti-cancer drug, a combination of Uracil and Tegaful) 400 mg day-1 for 1 year after surgery; group B). Stage II or IIIA disease patients (n=95) were randomly assigned to surgery alone (group C) or surgery followed by chemotherapy (two 28-day courses of cisplatin 80 mg m-2 on day 1 plus vindesine 3 mg m-2 on days 1 and 8, followed by UFT 400 mg day-1 for at least 1 year; group D). Eight-year overall survival rate in patients with stage I disease was 74.2% (95% confidence interval (CI): 64.4-84.0%) in group B and 57.6% (95% CI: 46.4-68.8%) in group A (P=0.045 by log-rank test). In patients with stage II and IIIA disease, no difference was found between groups C and D. Analysis according to DNA ploidy pattern revealed no difference between the groups. Postoperative chemotherapy with UFT was suggested to be useful in patients with completely resected stage I NSCLC. No difference was seen in relation to DNA pattern in any treatment group.
| S-EPMC2360551 | biostudies-other
Project description:Purpose: The JBR.10 trial demonstrated benefit from adjuvant cisplatin/vinorelbine (ACT) in early-stage non-small-cell lung cancer (NSCLC). We hypothesized that expression profiling may identify stage-independent subgroups who might benefit from ACT. Patients and Methods: Gene expression profiling was conducted on mRNA from 133 frozen JBR.10 tumor samples (62 observation [OBS], 71 ACT). The minimum gene set that was selected for the greatest separation of good and poor prognosis patient subgroups in OBS patients was identified. The prognostic value of this gene signature was tested in four independent published microarray data sets and by quantitative reverse-transcriptase polymerase chain reaction (RT-qPCR). Results: A 15-gene signature separated OBS patients into high-risk and low-risk subgroups with significantly different survival (hazard ratio [HR], 15.02; 95% CI, 5.12 to 44.04; P .001; stage I HR, 13.31; P .001; stage II HR, 13.47; P .001). The prognostic effect was verified in the same 62 OBS patients where gene expression was assessed by qPCR. Furthermore, it was validated consistently in four separate microarray data sets (total 356 stage IB to II patients without adjuvant treatment) and additional JBR.10 OBS patients by qPCR (n 19). The signature was also predictive of improved survival after ACT in JBR.10 high-risk patients (HR, 0.33; 95% CI, 0.17 to 0.63; P .0005), but not in low-risk patients (HR, 3.67; 95% CI, 1.22 to 11.06; P = .0133; interaction P .001). Significant interaction between risk groups and ACT was verified by qPCR. Conclusion: This 15-gene expression signature is an independent prognostic marker in early-stage, completely resected NSCLC, and to our knowledge, is the first signature that has demonstrated the potential to select patients with stage IB to II NSCLC most likely to benefit from adjuvant chemotherapy with cisplatin/vinorelbine.
2010-09-09 | GSE14814 | GEO
Project description:Postoperative non-small cell lung cancer (NSCLC) patients require adjuvant therapy to improve their prognosis. In this study, we investigated the efficacy of a sequential combination of autologous cellular immunotherapy (CIT) and chemotherapy for postoperative NSCLC. This retrospective study included 120 postoperative NSCLC patients: 60 cases received only chemotherapy; 33 cases received chemotherapy and sequential CIT with cytokine-induced killer (CIK) cells; and 27 cases received chemotherapy and sequential CIT with alternate CIK and natural killer (NK) cells. Survival analysis showed significantly higher overall survival rates in the CIT group compared with the control group. Overall survival was higher in patients who received CIT with alternate CIK and NK cells than those who received treatment with only CIK cells. Multivariate analysis showed that adjuvant CIT was an independent prognostic factor for overall survival of patients with NSCLC. In subgroup analyses, adjuvant CIT significantly improved the overall survival of patients with less than 60 y old and positive lymph node. In conclusions, these data indicate that adjuvant CIT, especially with alternate application of CIK and NK cells, is an effective therapeutic approach to prolong survival of patients with NSCLC, particularly for patients ?60 y old with positive lymph nodes.
| S-EPMC4570139 | biostudies-literature
Project description:Adjuvant cisplatin-based chemotherapy only marginally improves survival in patients with completely resected non-small-cell lung cancer (NSCLC). We have evaluated the predictive value of mutations in TP53, encoding the tumour suppressor p53, in the International Adjuvant Lung Cancer Trial (IALT), a randomized trial of adjuvant cisplatin-based chemotherapy against observation. TP53 (exons 4-8) was sequenced in 524 archived specimens of IALT patients with a median follow-up of 7.5 years. Predictive analyses were based on Cox models adjusted for clinical and pathological variables. P-values ? 0.01 were considered as significant. Mutations were detected in 221 patients (42%) and had no predictive value for the effect of chemotherapy (interaction between TP53 and treatment: p = 0.17 for Overall Survival (OS); p = 0.06 for Disease-Free Interval, (DFS)). However, among patients with mutations, outcome appeared worse in treatment compared to observation arms (HR for OS = 1.36 (95% CI [0.97-1.31), p = 0.08; DFS = 1.40 (95% CI [1.01-1.95]), p = 0.04). When grouping mutations into classes according to predicted effects on protein structure, the tendency towards worse outcomes was restricted to "structure" mutations affecting residues of the hydrophobic core that are not located at the p53 protein-DNA interface (HR for death in this class vs wild-type T53 = 1.66; 95% CI [1.10-2.52], p = 0.02). Overall, TP53 mutations are not significant predictors of outcome in this trial of cisplatin-based chemotherapy, although a specific class of structural mutations may be associated with a tendency towards worse outcomes upon treatment.
| S-EPMC5528648 | biostudies-literature