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The role of postoperative radiotherapy for completely resected pIIIA-N2 non-small cell lung cancer patients with different clinicopathological features: a systemic review and meta-analysis.

ABSTRACT: Background: The role of postoperative radiotherapy (PORT) in completely resected pathological stage IIIA-N2 (pIIIA-N2) non-small cell lung cancer (NSCLC) remains controversial. This meta-analysis aimed to assess the effect of PORT in patients with pIIIA-N2 NSCLC on the basis of clinicopathological features. Methods: The PubMed, PubMed Central (PMC), Embase, Web of Science, and Cochrane Library were searched for relevant studies. The main outcomes were overall survival (OS) and disease-free survival (DFS), which were compared using the hazard ratio (HR). Results: One randomized trial and 12 retrospective studies were eligible for the analysis. PORT significantly improved both OS [HR = 0.85; 95% confidence interval (CI): 0.79-0.92] and DFS (HR = 0.57; 95% CI: 0.38-0.85) compared with non-PORT treatment in patients with multiple N2 metastases or multiple N2 station involvement. No significant difference in either OS (HR = 1.03; 95% CI: 0.86-1.24) or DFS (HR = 1.08; 95% CI: 0.70-1.65) was found between PORT and non-PORT groups for patients with single N2 station involvement. No significant heterogeneity was observed. No significant differences in OS were observed between PORT and non-PORT groups for patients of different ages, sex, tumor sizes or pT stages, and histological types. Conclusions: The findings of this meta-analysis supported a role for PORT in patients with completely resected pIIIA-N2 NSCLC having multiple N2 metastases and favored withholding PORT to patients with single N2 station involvement. Further prospective randomized controlled trials are needed to confirm the findings.

SUBMITTER: Liu T

PROVIDER: S-EPMC6692616 | biostudies-literature | 2019

REPOSITORIES: biostudies-literature

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The role of postoperative radiotherapy for completely resected pIIIA-N2 non-small cell lung cancer patients with different clinicopathological features: a systemic review and meta-analysis.

Liu Tingting T Mu Yanshu Y Dang Jun J Li Guang G

Journal of Cancer 20190624 17

<b>Background</b>: The role of postoperative radiotherapy (PORT) in completely resected pathological stage IIIA-N2 (pIIIA-N2) non-small cell lung cancer (NSCLC) remains controversial. This meta-analysis aimed to assess the effect of PORT in patients with pIIIA-N2 NSCLC on the basis of clinicopathological features. <b>Methods</b>: The PubMed, PubMed Central (PMC), Embase, Web of Science, and Cochrane Library were searched for relevant studies. The main outcomes were overall survival (OS) and dise ...[more]

PMID: 31417638

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Project description:Background: The clinical value and delineation of clinical target volume (CTV) of postoperative radiotherapy (PORT) in completely resected (y)pN2 non-small cell lung cancer (NSCLC) remain controversial. Investigations specifically focusing on the cumulative incidence and prognostic significance of initial disease recurrence at the supraclavicular region (SCR) in this disease population are seldom reported. Methods: Consecutive patients with curatively resected (y)pN2 NSCLC who received adjuvant chemotherapy from January 2013 to December 2018 at our cancer center were retrospectively examined. Disease recurrence at the surgical margin, ipsilateral hilum, and/or mediastinum was defined as loco-regional recurrence (LRR). Disease recurrence beyond LRR and SCR, was defined as distant metastasis (DM). Overall survival (OS1 and OS2) were calculated from surgery and disease recurrence to death of any cause, in the entire cohort and in patients with recurrent disease, respectively. Results: Among the 311 patients enrolled, PORT without elective supraclavicular nodal irradiation (ESRT) was performed in 94 patients and neoadjuvant chemotherapy was administered in 31 patients. With a median follow-up of 26 months, 203 patients developed recurrent disease, including 27 SCRs, among which 16 were without DM and 22 involved the ipsilateral supraclavicular region. The 1, 3, and 5-year cumulative incidence of SCR were 6.53, 13.0, and 24.7%, respectively. Chosen DM as a competing event, cN2, ypN2, not receiving lobectomy, and negative expression of CK7 were significantly associated with SCR using the univariate competing risk analysis, while ypN2 was identified as the only independent risk factor of SCR (p = 0.012). PORT significantly reduced LRR (p = 0.031) and prolonged OS1 (p = 0.018), but didn't impact SCR (p = 0.254). Pattern of failure analyses indicated that the majority of LRRs developed within the actuarial or virtual CTV of PORT, and 15 of the 22 ipsilateral SCRs could be covered by the virtual CTV of proposed ESRT. In terms of OS2, patients who developed SCR but without DM had intermediate prognosis, compared with those who had DM (p = 0.009) and those who had only LRR (p = 0.048). Conclusions: SCR is not uncommon and has important prognostic significance in completely resected (y)pN2 NSCLC. The clinical value of PORT and ESRT in such patients need to be further investigated.

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.

Project description:ImportanceThe role of postoperative radiotherapy (PORT) has not been well defined in resected pIIIA-N2 non-small cell lung cancer (NSCLC).ObjectiveTo evaluate the effect of PORT using modern techniques on survival and safety in patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy.Design, setting, and participantsThe PORT-C randomized clinical trial was conducted in 394 patients with pIIIA-N2 NSCLC treated with complete resection and 4 cycles of platinum-based chemotherapy between January 2009 and December 2017. Data were analyzed between March 2019 and December 2020.InterventionsPatients were randomized equally into the PORT arm (n = 202) or the observation arm (n = 192). The total dose of PORT was 50 Gy.Main outcomes and measuresThe primary end point was disease-free survival (DFS). Secondary end points included overall survival (OS), locoregional recurrence-free survival (LRFS), distant metastasis-free survival, and toxic effects.ResultsIn total, 394 patients were enrolled and 364 were eligible, with a median (range) age of 55 (25-70) years. There were 202 (55.5%) male and 162 (44.5%) female patients. The median follow-up was 46.0 (95% CI, 41.9-51.4) months, and 230 DFS events were reported. There were 184 patients in the PORT arm and 180 patients in the observation arm. The 3-year DFS rates were 40.5% with PORT vs 32.7% with observation (median, 22.1 vs 18.6 months), and the difference in DFS was not statistically significant without adjustment (hazard ratio [HR], 0.84; 95% CI, 0.65-1.09; P = .20), though it was significant with preplanned yet exploratory analysis (stratified analysis by the number of detected lymph nodes and positive lymph nodes, HR, 0.75; log-rank P = .04). The 3-year OS rates were 78.3% vs 82.8% (HR, 1.02; P = .93), and LRFS was 66.5% vs 59.7% (HR, 0.71; 95% CI, 0.51-0.97; P = .03), respectively. For 310 per-protocol patients (140 with PORT and 170 with observation), PORT significantly improved DFS (42.8% vs 30.6%; HR, 0.75; 95% CI, 0.57-1.00; P = .05) but not OS (HR, 0.83; 95% CI, 0.53-1.30; P = .41). The 3-year local recurrence only rates were 9.5% and 18.3% in the 2 arms, respectively (Fine-Gray HR, 0.55; Gray test P = .04). No radiotherapy-related grade 4 or 5 adverse event was observed.Conclusions and relevanceIn this phase 3 randomized clinical trial of patients with pIIIA-N2 NSCLC after complete resection and adjuvant chemotherapy, PORT did not improve DFS. Further studies exploring patients who might best benefit from PORT are needed.Trial registrationClinicalTrials.gov Identifier: NCT00880971.

Dataset Information

The role of postoperative radiotherapy for completely resected pIIIA-N2 non-small cell lung cancer patients with different clinicopathological features: a systemic review and meta-analysis.

Publications

The role of postoperative radiotherapy for completely resected pIIIA-N2 non-small cell lung cancer patients with different clinicopathological features: a systemic review and meta-analysis.

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