Circulating cell free DNA during definitive chemo-radiotherapy in non-small cell lung cancer patients - initial observations.

BACKGROUND: The overall aim was to investigate the change over time in circulating cell free DNA (cfDNA) in patients with locally advanced non-small cell lung cancer (NSCLC) undergoing concurrent chemo-radiotherapy. Furthermore, to assess the possibility of detecting circulating cell free tumor DNA (ctDNA) using shallow whole genome sequencing (sWGS) and size selection. METHODS: Ten patients were included in a two-phase study. The first four patients had blood samples taken prior to a radiation therapy (RT) dose fraction and at 30 minutes, 1 hour and 2 hours after RT to estimate the short-term dynamics of cfDNA concentration after irradiation. The remaining six patients had one blood sample taken on six treatment days 30 minutes post treatment to measure cfDNA levels. Presence of ctDNA as indicated by chromosomal aberrations was investigated using sWGS. The sensitivity of this method was further enhanced using in silico size selection. RESULTS: cfDNA concentration from baseline to 120 min after therapy was stable within 95% tolerance limits of +/- 2 ng/ml cfDNA. Changes in cfDNA were observed during therapy with an apparent qualitative difference between adenocarcinoma (average increase of 0.69 ng/ml) and squamous cell carcinoma (average increase of 4.0 ng/ml). Tumor shrinkage on daily cone beam computer tomography scans during radiotherapy did not correlate with changes in concentration of cfDNA. CONCLUSION: Concentrations of cfDNA remain stable during the first 2 hours after an RT fraction. However, based on the sWGS profiles, ctDNA represented only a minor fraction of cfDNA in this group of patients. The detection sensitivity of genomic alterations in ctDNA strongly increases by applying size selection

Outcome-based multiobjective optimization of lymphoma radiation therapy plans

At its core, radiation therapy (RT) requires balancing therapeutic effects against risk of adverse events in cancer survivors. The radiation oncologist weighs numerous disease and patient-level factors when considering the expected risk–benefit ratio of combined treatment modalities. As part of this, RT plan optimization software is used to find a clinically acceptable RT plan delivering a prescribed dose to the target volume while respecting pre-defined radiation dose–volume constraints for selected organs at risk. The obvious limitation to the current approach is that it is virtually impossible to ensure the selected treatment plan could not be bettered by an alternative plan providing improved disease control and/or reduced risk of adverse events in this individual. Outcome-based optimization refers to a strategy where all planning objectives are defined by modeled estimates of a specific outcome’s probability. Noting that various adverse events and disease control are generally incommensurable, leads to the concept of a Pareto-optimal plan: a plan where no single objective can be improved without degrading one or more of the remaining objectives. Further benefits of outcome-based multiobjective optimization are that quantitative estimates of risks and benefit are obtained as are the effects of choosing a different trade-off between competing objectives. Furthermore, patient-level risk factors and combined treatment modalities may be integrated directly into plan optimization. Here, we present this approach in the clinical setting of multimodality therapy for malignant lymphoma, a malignancy with marked heterogeneity in biology, target localization, and patient characteristics. We discuss future research priorities including the potential of artificial intelligence

Additional file 2: Figure S2. of Fractionated palliative thoracic radiotherapy in non-small cell lung cancer – futile or worth-while?

Cox regression analysis showing correlation between OS and age > or <70 years from prescription of PTR to death. There was a trend towards better OS and high age, but this was not statistical significant. Age > 70 years had a HR = 0.79 (95% CI: 0.58-1.09), p = 0.15. (DOCX 25 kb

Additional file 3: Figure S3. of Fractionated palliative thoracic radiotherapy in non-small cell lung cancer – futile or worth-while?

Cox regression analysis showing correlation between OS and radiotherapy schedules 25Gy/5F or 30Gy/10F from prescription of PTR to death. There was a trend towards better OS with 30Gy/10F but this was not statistical significant. 30Gy/10F had a HR = 0.74 (95% CI: 0.52-1.04), p = 0.08 (DOCX 25 kb