Prediction of post-radiotherapy recurrence volumes in head and neck squamous cell carcinoma using 3D U-Net segmentation

Locoregional recurrences (LRR) are still a frequent site of treatment failure for head and neck squamous cell carcinoma (HNSCC) patients. Identification of high risk subvolumes based on pretreatment imaging is key to biologically targeted radiation therapy. We investigated the extent to which a Convolutional neural network (CNN) is able to predict LRR volumes based on pre-treatment 18F-fluorodeoxyglucose positron emission tomography (FDG-PET)/computed tomography (CT) scans in HNSCC patients and thus the potential to identify biological high risk volumes using CNNs. For 37 patients who had undergone primary radiotherapy for oropharyngeal squamous cell carcinoma, five oncologists contoured the relapse volumes on recurrence CT scans. Datasets of pre-treatment FDG-PET/CT, gross tumour volume (GTV) and contoured relapse for each of the patients were randomly divided into training (n=23), validation (n=7) and test (n=7) datasets. We compared a CNN trained from scratch, a pre-trained CNN, a SUVmax threshold approach, and using the GTV directly. The SUVmax threshold method included 5 out of the 7 relapse origin points within a volume of median 4.6 cubic centimetres (cc). Both the GTV contour and best CNN segmentations included the relapse origin 6 out of 7 times with median volumes of 28 and 18 cc respectively. The CNN included the same or greater number of relapse volume POs, with significantly smaller relapse volumes. Our novel findings indicate that CNNs may predict LRR, yet further work on dataset development is required to attain clinically useful prediction accuracy

Dosimetric Analysis of Proximal Bronchial Tree Subsegments to Assess The Risk of Severe Toxicity After Stereotactic Body Radiation Therapy of Ultra-central Lung Tumors

Background and purpose Stereotactic body radiotherapy (SBRT) of ultra-central lung tumors (UCLT) is associated with an increased risk of severe toxicity. The aim of this study was to perform a detailed dosimetric analysis of the proximal bronchial tree (PBT) anatomical sub-segments to evaluate the safety of risk-adapted SBRT and to evaluate potential differences in radiation tolerance between PBT sub-segments. Material and methods Fifty-seven patients treated with SBRT for UCLT between 2014 and 2021 were included. UCLT were defined as tumor abutting or overlapping with the trachea, PBT, or esophagus. This study analyzed overall survival, local control, progression-free survival, and grade ≥3 toxicity events. Bayesian inference was used to build a dose-response model with upper limits for toxicity. Results Twenty-seven (47.4%) of the irradiated lesions were primary or locoregionally recurrent NSCLC and 30 (52.6%) oligometastases. All patients were treated with risk-adapted SBRT of median 45.0 Gy (range: 30.0-60.0 Gy) in 8 or 10 fractions. Grade ≥3 radiation pneumonitis was observed in two patients (3.5%), while no bronchial stenosis, hemorrhage or fistula were observed. The dose-response model predicted a grade ≥3 toxicity (stenosis, hemorrhage or fistula) limited to 4.9% (0 - 11.4%) when delivering EQD2$\_$3 = 100 Gy to any location of the PBT (D0.2cc). Detailed dosimetric analysis of PBT substructures showed no variation in the dose-response model between the anatomical PBT sub-segments. Conclusion Risk-adapted SBRT regimens delivered in 8 or 10 fractions for ultra-central lung tumors resulted in high rates of local tumor control with low toxicity rates, without differences in radiation tolerance between the anatomical PBT sub-segments

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

Diminishing Returns From Ultrahypofractionated Radiation Therapy for Prostate Cancer

INTRODUCTION: More than a decade of randomized controlled trials in prostate cancer have established a positive radiation dose response at moderate doses and a consistently low α/β ratio in the linear quadratic model for moderate hypofractionation. The recently published large randomized trial of ultra-hypofractionated prostate cancer radiotherapy adds substantially to our current knowledge of dose-response and fractionation sensitivity. METHODS AND MATERIALS: Randomized trials of dose-escalation and hypofractionation of radiotherapy are meta-analyzed to yield the overall best estimate of the α/β ratio. Additionally, a putative saturation of dose effect previously reported at approximately 80 Gy EQD2 is investigated by mapping the relative effectiveness assessed at five years onto a single reference dose-response curve. RESULTS: Meta-analysis of 14 randomized trials including 13,384 patients yields a best estimate of α/β=1.6 Gy [95% CI: 1.3 to 2.0 Gy], but with highly significant heterogeneity (I(2)=70%, P=0.0005). Further analysis indicates an association between increasing dose per fraction in the experimental arm and increasing α/β ratio (slope: 0.6 Gy increase in α/β per Gy increase in fraction size, p=0.017). This deviation from the linear quadratic model could, however, also be explained by biochemical control maxing out at doses above approximately 80 Gy. CONCLUSIONS: Biochemical control data from randomized controlled trials of dose-per-fraction escalation in prostate cancer radiotherapy are inconsistent with the presence of a constant fractionation sensitivity in the LQ model and/or a monotonic dose response for biochemical control beyond 80 Gy equivalent dose. These observations have potential impact on the optimal doses in future trials as well as the interpretation of ongoing trials of ultra-hypofractionation