Remarkable progress in molecular analyses has improved our understanding of the evolution of cancer cells toward immune escape
. However, the spatial configurations of immune and stromal cells, which ...may shed light on the evolution of immune escape across tumor geographical locations, remain unaddressed. We integrated multiregion exome and RNA-sequencing (RNA-seq) data with spatial histology mapped by deep learning in 100 patients with non-small cell lung cancer from the TRACERx cohort
. Cancer subclones derived from immune cold regions were more closely related in mutation space, diversifying more recently than subclones from immune hot regions. In TRACERx and in an independent multisample cohort of 970 patients with lung adenocarcinoma, tumors with more than one immune cold region had a higher risk of relapse, independently of tumor size, stage and number of samples per patient. In lung adenocarcinoma, but not lung squamous cell carcinoma, geometrical irregularity and complexity of the cancer-stromal cell interface significantly increased in tumor regions without disruption of antigen presentation. Decreased lymphocyte accumulation in adjacent stroma was observed in tumors with low clonal neoantigen burden. Collectively, immune geospatial variability elucidates tumor ecological constraints that may shape the emergence of immune-evading subclones and aggressive clinical phenotypes.
Prophylactic irradiation to the chest wall after diagnostic or therapeutic procedures in patients with malignant pleural mesothelioma (MPM) has been a widespread practice across Europe, although the ...efficacy of this treatment is uncertain. In this study, we aimed to determine the efficacy of prophylactic radiotherapy in reducing the incidence of chest wall metastases (CWM) after a procedure in MPM.
After undergoing a chest wall procedure, patients with MPM were randomly assigned to receive prophylactic radiotherapy (within 42 days of the procedure) or no radiotherapy. Open thoracotomies, needle biopsies, and indwelling pleural catheters were excluded. Prophylactic radiotherapy was delivered at a dose of 21 Gy in three fractions over three consecutive working days, using a single electron field adapted to maximize coverage of the tract from skin surface to pleura. The primary outcome was the incidence of CWM within 6 months from random assignment, assessed in the intention-to-treat population. Stratification factors included epithelioid histology and intention to give chemotherapy.
Between July 30, 2012, and December 12, 2015, 375 patients were recruited from 54 centers and randomly assigned to receive prophylactic radiotherapy (n = 186) or no prophylactic radiotherapy (n = 189). Participants were well matched at baseline. No significant difference was seen in the incidence of CWM at 6 months between the prophylactic radiotherapy and no radiotherapy groups (no. %: 6 3.2
10 5.3, respectively; odds ratio, 0.60; 95% CI, 0.17 to 1.86;
= .44). Skin toxicity was the most common radiotherapy-related adverse event in the prophylactic radiotherapy group, with 96 patients (51.6%) receiving grade 1; 19 (10.2%), grade 2; and 1 (0.5%) grade 3 radiation dermatitis (Common Terminology Criteria for Adverse Events, version 4.0).
There is no role for the routine use of prophylactic irradiation to chest wall procedure sites in patients with MPM.
Dietetic assessment and intervention in lung cancer Phillips, Iain; Hug, Adele; Allan, Lindsey ...
Current opinion in supportive & palliative care,
2019-December, 2019-12-00, 20191201, Letnik:
13, Številka:
4
Journal Article
PURPOSE OF REVIEWSystemic therapy for lung cancer is increasing in intensity and duration. European nutrition guidelines suggest screening for weight loss and malnutrition, however acknowledges there ...is a lack of evidence. We discuss current data round this issue and identify opportunities for further research.
RECENT FINDINGSInternational guidelines now exist to aid the definition of weight loss in cancer, including cachexia, sarcopenia and malnutrition. These allow consistent definition of overlapping, but distinct clinical syndromes. Nutritional status can be assessed in a range of ways including questionnaires, functional assessments, blood markers, physical activity, weight and BMI. Weight loss is commonly associated with a proinflammatory state. Future treatment is likely to be a combination of dietetic support and pharmacological treatment of cachexia.
SUMMARYThere is a paucity of data on dietetic intervention. It is potentially quick, inexpensive and patient specific, using a holistic approach to aid patients who are malnourished or at risk of malnutrition. Lung cancer-related weight loss is common, further strategies are needed to effectively assess and intervene. Dietetic intervention has the potential to improve patients’ quality of life and outcomes.
Lung cancer is the leading cause of cancer mortality worldwide. Treatment pathways include regular cross-sectional imaging, generating large data sets which present intriguing possibilities for ...exploitation beyond standard visual interpretation. This additional data mining has been termed "radiomics" and includes semantic and agnostic approaches. Textural analysis (TA) is an example of the latter, and uses a range of mathematically derived features to describe an image or region of an image. Often TA is used to describe a suspected or known tumour. TA is an attractive tool as large existing image sets can be submitted to diverse techniques for data processing, presentation, interpretation and hypothesis testing with annotated clinical outcomes. There is a growing anthology of published data using different TA techniques to differentiate between benign and malignant lung nodules, differentiate tissue subtypes of lung cancer, prognosticate and predict outcome and treatment response, as well as predict treatment side effects and potentially aid radiotherapy planning. The aim of this systematic review is to summarize the current published data and understand the potential future role of TA in managing lung cancer.
Several studies have recently reported on the value of CT texture analysis in predicting survival, although the topic remains controversial, with further validation needed in order to consolidate the ...evidence base. The aim of this study was to investigate the effect of varying the input parameters in the Kaplan-Meier analysis, to determine whether the resulting P-value can be considered to be a robust indicator of the parameter's prognostic potential. A retrospective analysis of the CT-based normalised entropy of 51 patients with lung cancer was performed and overall survival data for these patients were collected. A normalised entropy cut-off was chosen to split the patient cohort into two groups and log-rank testing was performed to assess the survival difference of the two groups. This was repeated for varying normalised entropy cut-offs and varying follow-up periods. Our findings were also compared with previously published results to assess robustness of this parameter in a multi-centre patient cohort. The P-value was found to be highly sensitive to the choice of cut-off value, with small changes in cut-off producing substantial changes in P. The P-value was also sensitive to follow-up period, with particularly noisy results at short follow-up periods. Using matched conditions to previously published results, a P-value of 0.162 was obtained. Survival analysis results can be highly sensitive to the choice in texture cut-off value in dichotomising patients, which should be taken into account when performing such studies to avoid reporting false positive results. Short follow-up periods also produce unstable results and should therefore be avoided to ensure the results produced are reproducible. Previously published findings that indicated the prognostic value of normalised entropy were not replicated here, but further studies with larger patient numbers would be required to determine the cause of the different outcomes.
Rate of cachexia in lung cancer Hug, Adele; Phillips, Iain; Allan, Lindsey ...
European journal of surgical oncology,
November 2016, Letnik:
42, Številka:
11
Journal Article
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