Postoperative radiotherapy in resected non-small cell lung cancer: The never-ending story
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ABSTRACT:
SUBMITTER: Serrano J
PROVIDER: S-EPMC8546654 | biostudies-literature |
REPOSITORIES: biostudies-literature
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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:In the British feline breed a golden coat modification, called light-gold, akita or copper, was reported by breeders during the 2010s. This modification restricted eumelanin to the tip of the tail and hairs showed a wideband modification. Pedigree analyses revealed an autosomal recessive inheritance pattern. A single candidate region was identified using a genome-wide association study. Within that region, we identified CORIN (Corin, serine peptidase) as the strongest candidate gene, since two CORIN variants have previously been identified in Siberian cats with a golden phenotype. A homozygous CORIN:c.2425C>T nonsense variant was identified in copper British cats. Segregation of the variant was consistent with recessive inheritance. This nonsense CORIN:c.2425C>T variant, located in CORIN exon 19, was predicted to produce a truncated CORIN protein - CORIN:p.(Arg809Ter) - that would lack part of the scavenger receptor domain and the trypsine-like serine protease catalytic domain. All 30 copper cats were T/T homozygous for the variant, which was also found in 20 C/T heterozygous British control cats but was absent in 340 cats from the 99 Lives dataset. Finally, genotyping of 218 cats from 12 breeds failed to identify carriers in cats from other breeds. We propose that this third CORIN:c.2425C>T variant represents the wbBSH (British recessive wideband) allele in the domestic cat.
| S-EPMC9544971 | 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: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:Glaucoma is one of the principal causes of irreversible blindness worldwide. Yet, intraocular pressure (IOP) is the main modifiable risk factor for disease progression. In the never-ending challenge to develop new and effective drugs, several molecules have been tested as anti-glaucoma agents thanks to their pressure-lowering capabilities. Among these molecules, the cannabinoids have been investigated as possible anti-glaucoma drugs since the early 1970s. Cannabinoids are a large class of chemical compounds that exploit their effects by interaction with cannabinoid receptors 1 and 2. These receptors are widely expressed in the human retina where they may influence important functions such as photo-transduction, amacrine cell network maintenance, and IOP regulation. Therefore, in past years several studies have been conducted in order to assess the IOP lowering effects of cannabinoids. PRISMA guidelines have been used to perform a literature search on Pubmed and Scopus aiming to investigate the mechanism of IOP lowering effects and the potential benefits of orally administered, inhaled, topical, and intravenous cannabinoids in the treatment of glaucoma patients.
| S-EPMC7763320 | biostudies-literature
Project description:Homology modelling is normally the technique of choice when experimental structure data are not available but three-dimensional coordinates are needed, for example, to aid with detailed interpretation of results of spectroscopic studies. Herein, the state of the art of homology modelling will be described in the light of a series of recent developments, and an overview will be given of the problems and opportunities encountered in this field. The major topic, the accuracy and precision of homology models, will be discussed extensively due to its influence on the reliability of conclusions drawn from the combination of homology models and spectroscopic data. Three real-world examples will illustrate how both homology modelling and spectroscopy can be beneficial for (bio)medical research.
| S-EPMC2841279 | 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:IntroductionThe positive-to-resected lymph node ratio (LNR) predicts survival in many cancers, but little information is available on its value for patients with N2 NSCLC who receive postoperative radiotherapy (PORT) after resection. We tested the applicability of prognostic scoring models and heat mapping to predict overall survival (OS) and cancer-specific survival (CSS) in patients with resected N2 NSCLC and PORT.MethodsOur test cohort comprised patients identified from the Surveillance, Epidemiology, and End Results database with N2 NSCLC who received resection and PORT in 2000-2014. Prognostic scoring models were developed to predict OS and CSS using Cox regression; heat maps were constructed with corresponding survival probabilities. Recursive partitioning analysis was applied to the Surveillance, Epidemiology, and End Results data to identify the optimal LNR cutoff point. Models and cutoff points were further tested in 183 similar patients treated at The University of Texas M. D. Anderson Cancer Center in 2000-2015.ResultsMultivariate analyses revealed that low LNR independently predicted better OS and CSS in patients with resected N2 NSCLC who received PORT.ConclusionsLNR can be used to predict survival of patients with resected N2 NSCLC followed by PORT. This approach, which to our knowledge is the first application of heat mapping of positive and negative lymph nodes, was effective in estimating 3-, 5-, and 10-year OS probabilities.
| S-EPMC6552655 | biostudies-literature
Project description:(1) Purpose: To investigate the effects of the time interval between initiation of adjuvant chemotherapy and radiotherapy on survival outcomes in patients with completely resected stage IIIA pN2 non-small-cell lung cancer (NSCLC); (2) Methods: Data on 2515 patients with completely resected stage IIIA pN2 NSCLC in 2007-2017 were extracted from the Taiwan Cancer Registry Database. The survival outcomes in patients who underwent concurrent chemoradiotherapy (CCRT) and sequential chemotherapy and radiotherapy (SCRT) with either a short (SCRT1) or long (SCRT2) interval between treatments were estimated using Kaplan-Meier, Cox regression, and propensity score matching (PSM); (3) Results: Multivariate analyses of OS showed that SCRT2 (hazard ratio [HR] 0.64, p = 0.017) was associated with improved overall survival (OS). After PSM, the median OS periods were 64 and 75 months in the SCRT1 and SCRT2 groups, respectively, which differed significantly from that of 58 months in the CCRT group (p = 0.003). In elderly patients, SCRT2 significantly improved survival relative to CCRT before PSM (p = 0.024) and after PSM (p = 0.002); (4) Conclusions: A longer interval between initiation of adjuvant chemotherapy and postoperative radiotherapy (PORT; SCRT2) improved OS relative to CCRT; the benefits were greater in elderly patients (age >60 years).
| S-EPMC8160867 | biostudies-literature