Preoperative and postoperative radiotherapy (RT) for non-small cell lung cancer: still an open question.
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ABSTRACT:
SUBMITTER: Van Houtte P
PROVIDER: S-EPMC8107767 | biostudies-literature | 2021 Apr
REPOSITORIES: biostudies-literature
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Preoperative and postoperative radiotherapy (RT) for non-small cell lung cancer: still an open question.
Van Houtte Paul P Moretti Luigi L Charlier Florian F Roelandts Martine M Van Gestel Dirk D
Translational lung cancer research 20210401 4
Preoperative and postoperative radiotherapy (PORT) with or without chemotherapy has been used in non-small cell lung cancer (NSCLC) for decades. Numerous trials have investigated the potential survival benefit of this strategy, but despite greater knowledge of the disease, considerable technological developments in imaging and radiotherapy, and significant progress in surgery, many questions remain unsolved. In this review, we summarize the current knowledge on this problem and discuss issues wh ...[more]
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Project description:BACKGROUND:The role of postoperative radiotherapy (PORT) in the treatment of patients with completely resected non-small cell lung cancer (NSCLC) was not clear. A systematic review and individual participant data meta-analysis was undertaken to evaluate available evidence from randomised controlled trials (RCTs). These results were first published in Lung Cancer in 2013. OBJECTIVES:To evaluate the effects of PORT on survival and recurrence in patients with completely resected NSCLC. To investigate whether predefined patient subgroups benefit more or less from PORT. SEARCH METHODS:We supplemented MEDLINE and CANCERLIT searches (1965 to 8 July 2016) with information from trial registers, handsearching of relevant meeting proceedings and discussion with trialists and organisations. SELECTION CRITERIA:We included trials of surgery versus surgery plus radiotherapy, provided they randomised participants with NSCLC using a method that precluded prior knowledge of treatment assignment. DATA COLLECTION AND ANALYSIS:We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. We sought data on all participants from those responsible for the trial. We obtained updated individual participant data (IPD) on survival and date of last follow-up, as well as details on treatment allocation, date of randomisation, age, sex, histological cell type, stage, nodal status and performance status. To avoid potential bias, we requested information on all randomised participants, including those excluded from investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival. MAIN RESULTS:We identified 14 trials evaluating surgery versus surgery plus radiotherapy. Individual participant data were available for 11 of these trials, and our analyses are based on 2343 participants (1511 deaths). Results show a significant adverse effect of PORT on survival, with a hazard ratio of 1.18, or an 18% relative increase in risk of death. This is equivalent to an absolute detriment of 5% at two years (95% confidence interval (CI) 2% to 9%), reducing overall survival from 58% to 53%. Subgroup analyses showed no differences in effects of PORT by any participant subgroup covariate.We did not undertake analysis of the effects of PORT on quality of life and adverse events. Investigators did not routinely collect quality of life information during these trials, and it was unlikely that any benefit of PORT would offset the observed survival disadvantage. We considered risk of bias in the included trials to be low. AUTHORS' CONCLUSIONS:Results from 11 trials and 2343 participants show that PORT is detrimental to those with completely resected non-small cell lung cancer and should not be used in the routine treatment of such patients. Results of ongoing RCTs will clarify the effects of modern radiotherapy in patients with N2 tumours.
| S-EPMC6457851 | biostudies-literature
Project description:BACKGROUND:The role of postoperative radiotherapy (PORT) in the treatment of patients with completely resected non-small cell lung cancer (NSCLC) was not clear. A systematic review and individual participant data meta-analysis was undertaken to evaluate available evidence from randomised controlled trials (RCTs). These results were first published in Lung Cancer in 2013. OBJECTIVES:To evaluate the effects of PORT on survival and recurrence in patients with completely resected NSCLC. To investigate whether predefined patient subgroups benefit more or less from PORT. SEARCH METHODS:We supplemented MEDLINE and CANCERLIT searches (1965 to 8 July 2016) with information from trial registers, handsearching of relevant meeting proceedings and discussion with trialists and organisations. SELECTION CRITERIA:We included trials of surgery versus surgery plus radiotherapy, provided they randomised participants with NSCLC using a method that precluded prior knowledge of treatment assignment. DATA COLLECTION AND ANALYSIS:We carried out a quantitative meta-analysis using updated information from individual participants from all randomised trials. We sought data on all participants from those responsible for the trial. We obtained updated individual participant data (IPD) on survival and date of last follow-up, as well as details on treatment allocation, date of randomisation, age, sex, histological cell type, stage, nodal status and performance status. To avoid potential bias, we requested information on all randomised participants, including those excluded from investigators' original analyses. We conducted all analyses on intention-to-treat on the endpoint of survival. MAIN RESULTS:We identified 14 trials evaluating surgery versus surgery plus radiotherapy. Individual participant data were available for 11 of these trials, and our analyses are based on 2343 participants (1511 deaths). Results show a significant adverse effect of PORT on survival, with a hazard ratio of 1.18, or an 18% relative increase in risk of death. This is equivalent to an absolute detriment of 5% at two years (95% confidence interval (CI) 2% to 9%), reducing overall survival from 58% to 53%. Subgroup analyses showed no differences in effects of PORT by any participant subgroup covariate.We did not undertake analysis of the effects of PORT on quality of life and adverse events. Investigators did not routinely collect quality of life information during these trials, and it was unlikely that any benefit of PORT would offset the observed survival disadvantage. We considered risk of bias in the included trials to be low. AUTHORS' CONCLUSIONS:Results from 11 trials and 2343 participants show that PORT is detrimental to those with completely resected non-small cell lung cancer and should not be used in the routine treatment of such patients. Results of ongoing RCTs will clarify the effects of modern radiotherapy in patients with N2 tumours.
| S-EPMC5642866 | biostudies-literature
Project description:BACKGROUND:The role of postoperative radiotherapy (PORT) in patients with clinical stage III-N2 (cIII-N2) non-small cell lung cancer (NSCLC) treated with induction chemotherapy and surgical resection with persistent ypN2 disease is not well established. METHODS:We retrospectively reviewed a prospectively maintained database for patients with cIII-N2 NSCLC who underwent induction chemotherapy followed by resection (2004-2016). Exclusion criteria included induction radiotherapy, non-biopsy-confirmed cN2 disease, incomplete resection, ypN0/1, and nonanatomic resection. The primary outcome was locoregional recurrence (LR); secondary outcomes were disease-free survival (DFS), lung cancer-specific death (LCSD), and overall survival (OS). Associations between variables and outcomes were assessed using Fine and Gray competing risk regression for LR/LCSD and Cox proportional hazard models for survival. RESULTS:Of the 501 patients identified with cIII-N2 disease, 99 met the inclusion criteria. Median follow-up was 25 months (range, 3-137 months). Sixty-nine patients (70%) received PORT. Sixty (61%) developed a recurrence: 3 (5%) with an initial isolated LR and 57 (95%) with an initial distant recurrence. On multivariable analysis, PORT was not associated with LR (HR, 0.51 [95% CI, 0.22-1.21], p = 0.13). PORT was also not associated with DFS (p = 0.6) or LCSD (p = 0.1). PORT was associated with improved 3-year OS (55% [95% CI, 42%-71%]) versus the no-PORT group (50% [95% CI, 34%-74%]) (p = 0.04). CONCLUSIONS:PORT is not independently associated with decreased LR or improved DFS/LCSD in this patient population. Given that the predominant failure pattern was distant recurrence, future clinical trials should focus on adjuvant systemic therapies, which may decrease distant recurrences in ypN2 patients.
| S-EPMC6136648 | biostudies-literature
Project description:Cisplatin-based adjuvant chemotherapy remains the standard of care for patients with resected stage II or III non-small-cell lung cancer. However, biomarker-informed clinical trials are starting to push the management of early-stage lung cancer beyond cytotoxic chemotherapy. This review explores recent and ongoing studies focused on improving cytotoxic chemotherapy and incorporating targeted and immunotherapies in the management of early-stage, resectable lung cancer. Adjuvant osimertinib for patients with EGFR-mutant tumors, preoperative chemoimmunotherapy, and adjuvant immunotherapy could improve outcomes for selected patients with resectable lung cancer, and ongoing or planned studies leveraging biomarkers, immunotherapy, and targeted therapy may further improve survival. We also discuss the unique barriers associated with clinical trials of early-stage lung cancer and the need for innovative trial designs to overcome these challenges.
| S-EPMC8853628 | biostudies-literature
Project description:This manuscript collects in a joint and orderly manner the existing evidence at the present time about postoperative treatment with radiotherapy in non-small cell lung cancer. It also systematically reviews the current evidence, the international recommendations in the most relevant guidelines, the most controversial aspects in clinical and pathological staging, the specific technical aspects of radiotherapy treatment, and also collects all the potential risk factors that have been postulated as significant in the prognosis of these patients, evaluating the possibility of segmenting a particularly sensitive subpopulation with a high risk of relapse on which an adjuvant treatment with radiotherapy could have an impact on their clinical evolution. Finally, currently active trials that aspire to provide more evidence on this topic are reviewed.
| S-EPMC8546654 | biostudies-literature
Project description:BackgroundThe current staging system for completely resected pathologic N2 non-small cell lung cancer (NSCLC) treated with chemotherapy is not suitable for distinguishing those patients most likely to benefit from postoperative radiotherapy (PORT). This study aimed to construct a survival prediction model that will enable individualized prediction of the net survival benefit of PORT in patients with completely resected N2 NSCLC treated with chemotherapy.MethodsA total of 3,094 cases from between 2002 and 2014 were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Patient characteristics were included as covariates, and their association with overall survival (OS) with and without PORT was assessed. Data from 602 patients from China were included for external validation.ResultsAge, sex, the number of examined/positive lymph nodes, tumor size, the extent of surgery, and visceral pleural invasion (VPI) were significantly associated with OS (P<0.05). Two nomograms were developed based on clinical variables to estimate individuals' net survival difference attributable to PORT. The calibration curve showed excellent agreement between the OS predicted by the prediction model and that actually observed. In the training cohort, the C-index for OS was 0.619 [95% confidence interval (CI): 0.598-0.641] in the PORT group and 0.627 (95% CI: 0.605-0.648) in the non-PORT group. Results showed that PORT could improve OS [hazard ratio (HR): 0.861; P=0.044] for patients with a positive PORT net survival difference.ConclusionsOur practical survival prediction model can be used to make an individualized estimate of the net survival benefit of PORT for patients with completely resected N2 NSCLC who have been treated with chemotherapy.
| S-EPMC9922593 | biostudies-literature
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.
| S-EPMC7431951 | biostudies-literature
Project description:Background and Objectives: The research on the therapeutic effect of preoperative radiotherapy (PRRT) for patients with early non-small cell lung cancer (NSCLC) is still insufficient, and the impact of postoperative radiotherapy (PORT) on the prognosis of patients with early NSCLC remains controversial. We conducted this study to investigate the effect of PORT and PRRT on prognosis for these patients. Materials and Methods: In total, 3640 patients with stage II NSCLC who underwent a lobectomy or pneumonectomy were extracted from the Surveillance, Epidemiology, and End Results (SEER) database. Multivariate regression was adopted to identify the independent influence of PORT or PRRT on patients' prognosis. Subgroup analysis of survival was performed in patients with different combinations of key clinical features. We also used Kaplan-Meier analysis and competitive risk analysis to explore to which extent PORT or PRRT impacted the overall survival and cumulative mortality. Results: PORT was an independent risk factor of NSCLC-specific death among patients with N0 stage (HR, 1.648; 95% CI, 1.309-2.075, p < 0.001) and in N1 stage with <3 positive lymph nodes (HR, 2.698; 95% CI, 1.910-3.812, p < 0.001) in multivariate analysis. Findings from subgroup analysis for the risk of NSCLC-specific death, competitive risk analysis of NSCLC-specific cumulative mortality, and overall survival analysis also demonstrated PORT was detrimental to patients in these two subgroups above (p < 0.05). However, in patients with N1 stage with ≥3 positive lymph nodes, PORT may help prolong median survival. PRRT was an independent risk factor for NSCLC-specific death in multivariate analysis of patients with N0 stage (HR, 1.790; 95% CI, 1.201-2.668, p = 0.004), and significantly decreased overall survival in these patients (p < 0.001). Conclusion: PORT is associated with worse survival outcome and better cumulative mortality of stage II patients of NSCLC with N0 disease or N1 disease (<3 nodes), while PRRT is associated with reduced prognosis in patients with N0 stage. On the other hand, PORT may help to improve the prognosis of patients with N1 stage who have three or more lymph node metastases. Hence, PORT and PRRT should not be recommended for patients with N0 stage. However, in patients with "high volume" N1 stage, PORT might improve oncological outcomes.
| S-EPMC8624228 | biostudies-literature
Project description:With the high locoregional relapse rate and the improvement of radiation technology, postoperative radiotherapy (PORT) has been widely used in the treatment of completely resected stage IIIA-pN2 non-small-cell lung cancer (NSCLC). However, there is still no definitive consensus on clinical target volume for the pN2 subgroup. This review will discuss how to delineate the clinical target volume (CTV) for pN2 subgroups of IIIA-N2 NSCLC based on the published literature and to investigate the optimal PORT CTV in this cohort of patients. Besides overall survival (OS), locoregional recurrence (LR), and radiotherapy-related toxicity of this subset of the population in the modern PORT era, selection of proper patients will also be considered in this review. In summary, it is appropriate to include involved lymph node stations and uninvolved stations at high risk in PORT CTV for patients with pN2 disease when PORT is administered. PORT can reduce LR and has the potential to improve OS. In the current era of modern radiation technology, PORT can be administered safely with well-tolerated toxicity. Clinicopathological characteristics may be helpful in selecting proper candidates for PORT.
| S-EPMC4767117 | biostudies-literature
Project description:ObjectivesVideo-assisted thoracoscopic (VATS) lobectomy is increasingly accepted for the management of early-stage non-small cell lung cancer (NSCLC), but its role for locally advanced cancers has not been as well characterized. We compared outcomes of patients who received induction therapy followed by lobectomy, via VATS or thoracotomy.MethodsPerioperative complications and long-term survival of all patients with NSCLC who received induction chemotherapy (ICT) (with or without induction radiation therapy) followed by lobectomy from 1996-2012 were assessed using Kaplan-Meier and Cox proportional hazard analysis. Propensity score-matched comparisons were used to assess the potential impact of selection bias.ResultsFrom 1996 to 2012, 272 patients met inclusion criteria and underwent lobectomy after ICT: 69 (25%) by VATS and 203 (75%) by thoracotomy. An 'intent-to-treat' analysis was performed. Compared with thoracotomy patients, VATS patients had a higher clinical stage, were older, had greater body mass index, and were more likely to have coronary disease and chronic obstructive pulmonary disease. Induction radiation was used more commonly in thoracotomy patients [VATS 28% (n = 19) vs open 72% (n = 146), P < 0.001]. Thirty-day mortality was similar between the VATS [3% (n = 2)] and open [4% (n = 8)] groups (P = 0.69). Seven (10%) of the VATS cases were converted to thoracotomy due to difficulty in dissection from fibrotic tissue and adhesions (n = 5) or bleeding (n = 2); none of these conversions led to perioperative deaths. In univariate analysis, VATS patients had improved 3-year survival compared with thoracotomy (61% vs 43%, P = 0.010). In multivariable analysis, the VATS approach showed a trend towards improved survival, but this did not reach statistical significance (hazard ratio, 0.56; 95% confidence interval, 0.32-1.01; P = 0.053). Moreover, a propensity score-matched analysis balancing patient characteristics demonstrated that the VATS approach had similar survival to an open approach (P = 0.56).ConclusionsVATS lobectomy in patients treated with induction therapy for locally advanced NSCLC is feasible and effective and does not appear to compromise oncologic outcomes.
| S-EPMC4867396 | biostudies-literature