Background: The aim of this prognostic factor analysis was to investigate if a patient's self-reported health-related quality of life (HRQOL) provided independent prognostic information for survival ...in non-small cell lung cancer (NSCLC) patients. Patients and methods: Pretreatment HRQOL was measured in 391 advanced NSCLC patients using the EORTC QLQ-C30 and the EORTC Lung Cancer module (QLQ-LC13). The Cox proportional hazards regression model was used for both univariate and multivariate analyses of survival. In addition, a bootstrap validation technique was used to assess the stability of the outcomes. Results: The final multivariate Cox regression model retained four parameters as independent prognostic factors for survival: male gender with a hazard ratio (HR) = 1.32 (95% CI 1.03–1.69; P = 0.03); performance status (0 to 1 versus 2) with HR = 1.63 (95% CI 1.04–2.54; P = 0.032); patient's self-reported score of pain with HR= 1.11 (95% CI 1.07–1.16; P < 0.001) and dysphagia with HR = 1.12 (95% CI 1.04–1.21; P = 0.003). A 10-point shift worse in the scale measuring pain and dysphagia translated into an 11% and 12% increased in the likelihood of death respectively. A risk group categorization was also developed. Conclusion: The results suggest that patients' self-reported HRQOL provide independent prognostic information for survival. This finding supports the collection of such data in routine clinical practice.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Abstract Aim Non-small cell lung cancer (NSCLC)-patients with an epidermal growth factor receptor ( EGFR )-mutation have median progression-free survival (PFS) of 12 months on tyrosine kinase ...inhibitors (TKIs). Resistance is mediated by the EGFR T790M-mutation in the majority of patients. Longitudinal follow-up data are lacking. We retrospectively evaluated EGFR -mutated NSCLC-patients who were rebiopsied after TKI-treatment. A subgroup was sequentially rebiopsied along the course of the disease. Patients and methods Advanced EGFR -mutated NSCLC-patients who had both a pre-TKI biopsy and post-TKI biopsy available were included. Information on treatments and (re)biopsies was collected chronologically. Primary endpoint was the incidence of the T790M-mutation. Results Sixty-six patients fulfilled the inclusion criteria. In first post-TKI biopsies, T790M-mutation was detected in 34 patients (52%) of patients. Twenty-seven patients had subsequent post-TKI rebiopsies with mutation analysis available; in 10 patients (37%) the T790M-status in subsequent post-TKI rebiopsies was not consistent with the T790M-status of the first post-TKI biopsy. Progression free survival (PFS) on TKI-treatment was 12.0 months. Objective response rate on TKI-treatment was 81%. Patients developing T790M-mutation at post-TKI biopsy had longer median PFS compared to T790M-negative patients (14.2 versus 11.1 months respectively ( P = 0.034)) and longer overall survival (45.9 months versus 29.8 months respectively ( P = 0.213)). Transformation to SCLC was detected in 1 patient (2%). Conclusion Incidence of T790M-mutation at first post-TKI biopsy in this cohort of EGFR -mutated NSCLC-patients was 52%. Detection of T790M-mutation was not consistent over time; some patients who were T790M-positive at first post-TKI biopsy became T790M-negative in later post-TKI rebiopsies and vice versa. T790M-positive patients showed longer PFS than T790M-negative patients. Whether the low incidence of transformation to SCLC is justifying post-TKI rebiopsy in EGFR -mutated NSCLC-patients with acquired TKI-resistance in regular clinical practice is debatable.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UL, UM, UPCLJ, UPUK
Immunotherapy is regarded as one of the major breakthroughs in cancer treatment. Despite its success, only a subset of patients responds—urging the quest for predictive biomarkers. We hypothesize ...that artificial intelligence (AI) algorithms can automatically quantify radiographic characteristics that are related to and may therefore act as noninvasive radiomic biomarkers for immunotherapy response.
In this study, we analyzed 1055 primary and metastatic lesions from 203 patients with advanced melanoma and non-small-cell lung cancer (NSCLC) undergoing anti-PD1 therapy. We carried out an AI-based characterization of each lesion on the pretreatment contrast-enhanced CT imaging data to develop and validate a noninvasive machine learning biomarker capable of distinguishing between immunotherapy responding and nonresponding. To define the biological basis of the radiographic biomarker, we carried out gene set enrichment analysis in an independent dataset of 262 NSCLC patients.
The biomarker reached significant performance on NSCLC lesions (up to 0.83 AUC, P<0.001) and borderline significant for melanoma lymph nodes (0.64 AUC, P=0.05). Combining these lesion-wide predictions on a patient level, immunotherapy response could be predicted with an AUC of up to 0.76 for both cancer types (P<0.001), resulting in a 1-year survival difference of 24% (P=0.02). We found highly significant associations with pathways involved in mitosis, indicating a relationship between increased proliferative potential and preferential response to immunotherapy.
These results indicate that radiographic characteristics of lesions on standard-of-care imaging may function as noninvasive biomarkers for response to immunotherapy, and may show utility for improved patient stratification in both neoadjuvant and palliative settings.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Lung cancer has the highest mortality of all cancers. The aim of this study was to examine DNA hypermethylation in sputum and validate its diagnostic accuracy for lung cancer.
DNA hypermethylation of ...RASSF1A, APC, cytoglobin, 3OST2, PRDM14, FAM19A4 and PHACTR3 was analysed in sputum samples from symptomatic lung cancer patients and controls (learning set: 73 cases, 86 controls; validation set: 159 cases, 154 controls) by quantitative methylation-specific PCR. Three statistical models were used: (i) cutoff based on Youden's J index, (ii) cutoff based on fixed specificity per marker of 96% and (iii) risk classification of post-test probabilities.
In the learning set, approach (i) showed that RASSF1A was best able to distinguish cases from controls (sensitivity 42.5%, specificity 96.5%). RASSF1A, 3OST2 and PRDM14 combined demonstrated a sensitivity of 82.2% with a specificity of 66.3%. Approach (ii) yielded a combination rule of RASSF1A, 3OST2 and PHACTR3 (sensitivity 67.1%, specificity 89.5%). The risk model (approach iii) distributed the cases over all risk categories. All methods displayed similar and consistent results in the validation set.
Our findings underscore the impact of DNA methylation markers in symptomatic lung cancer diagnosis. RASSF1A is validated as diagnostic marker in lung cancer.
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DOBA, EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, IZUM, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, SIK, UILJ, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
•This ESMO Clinical Practice Guideline provides key recommendations and algorithms for managing oncogene-addicted mNSCLC.•ESMO-MCBS scores are given to describe the levels of evidence for treatment ...choices.•ESCAT scores are given to describe the evidence level for genomic alterations as biomarkers for using targeted therapies.•Recommendations are based on available scientific data and the authors’ collective expert opinion.•In clinical practice, all recommendations provided need to be discussed with patients in a shared decision-making approach.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Video-assisted thoracoscopic surgery (VATS) lobectomy and stereotactic ablative radiotherapy (SABR) are both used for early-stage non-small-cell lung cancer. We carried out a propensity score-matched ...analysis to compare locoregional control (LRC).
VATS lobectomy data from six hospitals were retrospectively accessed; SABR data were obtained from a single institution database. Patients were matched using propensity scores based on cTNM stage, age, gender, Charlson comorbidity score, lung function and performance score. Eighty-six VATS and 527 SABR patients were matched blinded to outcome (1:1 ratio, caliper distance 0.025). Locoregional failure was defined as recurrence in/adjacent to the planning target volume/surgical margins, ipsilateral hilum or mediastinum. Recurrences were either biopsy-confirmed or had to be PET-positive and reviewed by a tumor board.
The matched cohort consisted of 64 SABR and 64 VATS patients with the median follow-up of 30 and 16 months, respectively. Post-SABR LRC rates were superior at 1 and 3 years (96.8% and 93.3% versus 86.9% and 82.6%, respectively, P = 0.04). Distant recurrences and overall survival (OS) were not significantly different.
This retrospective analysis found a superior LRC after SABR compared with VATS lobectomy, but OS did not differ. Our findings support the need to compare both treatments in a randomized, controlled trial.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
To complement the existing treatment guidelines for all tumour types, ESMO organises consensus conferences to focus on specific issues in each type of tumour. The 2nd ESMO Consensus Conference on ...Lung Cancer was held on 11–12 May 2013 in Lugano. A total of 35 experts met to address several questions on non-small-cell lung cancer (NSCLC) in each of four areas: pathology and molecular biomarkers, first-line/second and further lines of treatment in advanced disease, early-stage disease and locally advanced disease. For each question, recommendations were made including reference to the grade of recommendation and level of evidence. This consensus paper focuses on first line/second and further lines of treatment in advanced disease.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Antibodies that target programmed death 1 (PD-1) or its ligand programmed death ligand 1 (PD-L1) have become a mainstay of first-line treatment of advanced/metastatic non-small-cell lung cancer ...(NSCLC) without targetable genetic alterations. In this review, we summarize results from recent clinical trials that have evaluated the anti-PD-1 antibodies pembrolizumab and nivolumab and the anti-PD-L1 antibodies atezolizumab and durvalumab as first-line treatment as monotherapy and in combination with chemotherapy, other immunotherapies, and antiangiogenesis agents. We discuss factors that may influence treatment selection, including patient baseline clinical and demographic characteristics, tumor histology, and biomarkers such as PD-L1 expression and tumor mutation burden. While immunotherapy has become a central component of first-line treatment of most patients with advanced NSCLC, important questions remain about how treatment should be managed for individual patients.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
•This ESMO Clinical Practice Guideline provides key recommendations and algorithms for managing non-oncogene-addicted mNSCLC.•ESMO-MCBS scores are given to describe the levels of evidence for ...treatment choices.•ESCAT scores are given to describe the evidence level for genomic alterations as biomarkers for using targeted therapies.•Recommendations are based on available scientific data and the authors’ collective expert opinion.•In clinical practice, all recommendations provided need to be discussed with patients in a shared decision-making approach.
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GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
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