Impact of Using Unedited CT-Based DIR-Propagated Autocontours on Online ART for Pancreatic SBRT

PURPOSE: To determine the dosimetric impact of using unedited autocontours in daily plan adaptation of patients with locally advanced pancreatic cancer (LAPC) treated with stereotactic body radiotherapy using tumor tracking. MATERIALS AND METHODS: The study included 98 daily CT scans of 35 LAPC patients. All scans were manually contoured (MAN), and included the PTV and main organs-at-risk (OAR): stomach, duodenum and bowel. Precision and MIM deformable image registration (DIR) methods followed by contour propagation were used to generate autocontour sets on the daily CT scans. Autocontours remained unedited, and were compared to MAN on the whole organs and at 3, 1 and 0.5 cm from the PTV. Manual and autocontoured OAR were used to generate daily plans using the VOLO™ optimizer, and were compared to non-adapted plans. Resulting planned doses were compared based on PTV coverage and OAR dose-constraints. RESULTS: Overall, both algorithms reported a high agreement between unclipped MAN and autocontours, but showed worse results when being evaluated on the clipped structures at 1 cm and 0.5 cm from the PTV. Replanning with unedited autocontours resulted in better OAR sparing than non-adapted plans for 95% and 84% plans optimized using Precision and MIM autocontours, respectively, and obeyed OAR constraints in 64% and 56% of replans. CONCLUSION: For the majority of fractions, manual correction of autocontours could be avoided or be limited to the region closest to the PTV. This practice could further reduce the overall timings of adaptive radiotherapy workflows for patients with LAPC

Inter- and intrafraction dose variations in robotic stereotactic body radiation therapy (SBRT) for perihilar cholangiocarcinoma in the prospective phase I STRONG trial

Using fiducial-marker-based robotic respiratory tumor tracking, we treated perihilar cholangiocarcinoma patients in the STRONG trial with 15 daily fractions of 4 Gy. For each of the included patients, in-room diagnostic-quality repeat CTs (rCT) were acquired pre- and post-dose delivery in 6 treatment fractions to analyze inter- and intrafraction dose variations. Planning CTs (pCTs) and rCTs were acquired in expiration breath-hold. Analogous to treatment, spine and fiducials were used to register rCTs with pCTs. In each rCT, all OARs were contoured, and the target was rigidly copied from the pCT based on grey values. The rCTs acquired were used to calculate the doses to be delivered through the treatment-unit settings. On average, target doses in rCTs and pCTs were similar. However, due to target displacements relative to the fiducials in rCTs, 10% of the rCTs showed PTV coverage losses of >10%. Although target coverages had been planned below desired values in order to protect OARs, many pre-rCTs contained OAR constraint violations: 44.4% for the 6 major constraints. Most OAR dose differences between pre- and post-rCTs were not statistically significant. The dose deviations observed in repeat CTs represent opportunities for more advanced adaptive approaches to enhancing SBRT treatment quality.</p

Technical feasibility of online adaptive stereotactic treatments in the abdomen on a robotic radiosurgery system

BACKGROUND AND PURPOSE: Stereotactic body radiotherapy (SBRT) has been proven to be beneficial for several disease sites in the (lower) abdomen. However, the quality of the treatment plan, based on a single planning computed tomography (CT), can be compromised due to large inter-fraction motion of the target and organs at risk (OARs) in this anatomical region. The aim of this study was to investigate the feasibility of online adaptive SBRT treatments on a robotic radiosurgery system and to record estimated total treatment times. MATERIALS AND METHODS: For two disease sites, locally advanced pancreatic cancer (LAPC) and oligometastatic lymph nodes, four patients with repeat CTs were included in the feasibility study. Quick treatment plan templates were generated based on the planning CT and validated by running them on the plan and fraction CTs. For two cases a dummy run was performed and the individual steps were timed. Dose delivery was the largest contributor to the total treatment time, followed by contour adaptation. RESULTS: Running the quick plan templates resulted in plans similar to unrestricted plans, obeying the OAR constraints. The dummy runs showed that online adaptive treatments were completed in 64 to 83 min respectively for oligometastases and LAPC, comparable to other clinically available solutions. CONCLUSIONS: This study showed the feasibility of online re-planning for two challenging disease sites within a clinically acceptable time frame on a robotic radiosurgery system, making use of commercially available elements that are not integrated by the vendor

Seminal vesicle inter- and intra-fraction motion during radiotherapy for prostate cancer: A review

A review of studies on seminal vesicle motion was performed to improve the understanding of these treatment uncertainties. This will aid planning target volume margin reduction, which is necessary for hypofractionation of high-risk prostate cancer. Embase, Medline, Web of science Core collection, Cochrane CENTRAL register of trials and Google scholar were searched for publications including 3D information on seminal vesicle motion. In total 646 publications were found of which 22 publications were eligible for inclusion. The mean, systematic and random error of inter- and intra-fraction translations are reported, as well as rotations. The translations of the seminal vesicles is smallest in the left–right direction, whereas the rotation was largest around this axis. Although rectal and bladder filling status were the main cause for seminal vesicle motion, no apparent effect on magnitude of motion was seen when different bladder and rectal preparation protocols were used. Inter- and intra-fraction motion of the seminal vesicles is significant. In the studies, systematic and random errors range between 1–7 mm and 1–5 mm respectively, and are largely uncorrelated to prostate motion. The maximum correlation between seminal vesicle and prostate motion was reported with an R2 of 0.7, while 3 other studies report lower and/or non-significant correlations. Five studies report a planning target volume margin of approximately 8 mm. This margin is in line with the results of four relevant dosimetric studies. Mitigating the inter- and intra-fraction motion of the seminal vesicles, including prostate tracking, has the potential to reduce planning target volume margins

Femtosecond water dynamics in reverse-micellar nanodroplets

Vibrational energy relaxation and ultrafast thermalization following impulsive excitation of the OH-stretching band of water nanodroplets confined to reverse micelles is studied by infrared pump–probe spectroscopy with sub-100 fs time resolution. The self-consistent analysis of experimental data for micelles diameters ranging from 1 to 10 nm as well as for bulk water reveals distinctly different vibrational lifetimes for the water molecules in the bulk-like core (270 fs) and in the surfactant vicinity (800 fs), which is a direct proof of a strongly disturbed hydrogen-bond network.

Photoswitchable molecular wires: From a sexithiophene to a dithienylethene and back

Photoswitchable dithienylethene groups, added to both α-ends of a sexithiophene molecular wire, switch reversibly between their open and closed forms upon irradiation. The open form has an excited state lifetime of 500 ps and is highly fluorescent, as is typical for oligothiophenes. In contrast the closed form is non-fluorescent and the excited state lifetime is a shorter by a factor of 100, reminiscent of a dithienylethene. In this system, we control the fundamental character of a molecular system through optical switching; toggling between a sexithiophene molecular wire and a dithienylethene reversibly.

Tunable Aggregation and Luminescence of Bis(diarylethene)sexithiophenes

Diarylethenes with two different side groups (phenyl and chloro) were appended to both α-ends of a sexithiophene unit. The temperature dependent aggregation properties for both compounds were characterized by steady state and transient absorption spectroscopy. The peripheral side groups show an unexpectedly significant influence on the electronic properties of the sexithiophene core. Furthermore, the relative influence of the phenyl and chloro substituents on the aggregation behavior observed is remarkable. The phenyl compound exhibits formation of H-aggregates over a narrow temperature range, between 240 and 200 K, typical of strong intermolecular interactions. In contrast, the chloro compound shows gradual aggregation over a wide temperature range, forming H-aggregates albeit with weaker intermolecular interactions. The results demonstrate that minor changes in the structure lead to tunability of the aggregation and corresponding luminescence properties of sexithiophenes in solution and hold particular relevance to supramolecular and polymer systems based on sexithiophene units.

Comparison of Daily Online Plan Adaptation Strategies for a Cohort of Pancreatic Cancer Patients Treated with SBRT

Purpose: To study the trade-offs of three online strategies to adapt treatment plans of patients with locally advanced pancreatic carcinoma (LAPC) treated using the CyberKnife with tumor tracking. Methods and Materials: A total of 35 planning computed tomography scans and 98 daily in-room computed tomography scans were collected from 35 patients with LAPC. Planned dose distributions, optimized with VOLO, were evaluated on manually contoured daily anatomies to collect daily doses. Three strategies were tested to adapt treatment plans: (1) unrestricted full replanning using a patient-specific plan template, (2) time-restricted replanning on organs at risk (OARs) within 3 cm from the planning target volume (PTV) structure, and (3) dose realignment optimization to stay within OAR constraints. Dose distributions resulting from each plan adaptation strategy were dosimetrically compared by means of gross tumor volume (GTV), PTV coverage, and OAR tolerances. Results: Planned doses did not result in dose-constraint violations for 28 of 98 daily anatomies. None of the suggested plan adaptation strategies improved planned doses significantly for this subset. For 70 of the 98 reported violations, the median (interquartile range) PTV coverage of the planned dose was 84% (76% to 86%). After plan adaptation, unrestricted replanning achieved clinically acceptable plans in 93% of these fractions, time-restricted replanning in 90%, and dose realignment in 74%, at median computational times of 8.5, 3, and 0.5 minutes. Over all 98 fractions, PTV coverage was reduced: –1% (–3% to 1%), –2% (–5% to 0%), and –2% (–8% to 0%) after each strategy, respectively. In 3 of 70 fractions, none of the suggested strategies achieved clinically acceptable OAR dose volumes. Conclusions: Unrestricted replanning was the most time-consuming method but reached the highest number of successfully adapted plans. Time-restricted replanning and dose realignment resulted in a high number of plans within dose constraints. Depending on the resources available, an adaptive strategy can be selected for each patient to address the specific anatomic challenges on the treatment day. The increase in the complexity of the strategy corresponds with an increasing number of successfully adapted plans

Ultrafast IR Spectroscopy on Aqueous Reverse-Micellar Nano-Droplets

The ultrafast dynamics of water nano-droplets (1-10 nm size) of the L2-phase of the ternary mixture H2O-AOT-CCl4 have been studied using frequency-resolved mid-infrared pump-probe spectroscopy in the spectral region of the OH-stretching vibration.