Search

Abstract Background Hypofractionated whole-breast irradiation is a standard adjuvant therapy for early-stage breast cancer. This study evaluates the plan quality and efficacy of an in-house-developed automated radiotherapy treatment planning algorithm for hypofractionated whole-breast radiotherapy. Methods A cohort of 99 node-negative left-sided breast cancer patients completed hypofractionated whole-breast irradiation with six-field IMRT for 42.56 Gy in 16 daily fractions from year 2016 to 2018 at a tertiary center were re-planned with an in-house-developed algorithm. The automated plan-generating C#-based program is developed in a Varian ESAPI research mode. The dose-volume histogram (DVH) and other dosimetric parameters of the automated and manual plans were directly compared. Results The average time for generating an autoplan was 5 to 6 min, while the manual planning time ranged from 1 to 1.5 h. There was only a small difference in both the gantry angles and the collimator angles between the autoplans and the manual plans (ranging from 2.2 to 5.3 degrees). Autoplans and manual plans performed similarly well in hotspot volume and PTV coverage, with the autoplans performing slightly better in the ipsilateral-lung-sparing dose parameters but were inferior in contralateral-breast-sparing. The autoplan dosimetric quality did not vary with different breast sizes, but for manual plans, there was worse ipsilateral-lung-sparing (V4Gy) in larger or medium-sized breasts than in smaller breasts. Autoplans were generally superior than manual plans in CI (1.24 ± 0.06 vs. 1.30 ± 0.09, p

Summary: Increased DNA replication and metastasis are hallmarks of cancer progression, while deregulated proliferation often triggers sustained replication stresses in cancer cells. How cancer cells overcome the growth stress and proceed to metastasis remains largely elusive. Proliferating cell nuclear antigen (PCNA) is an indispensable component of the DNA replication machinery. Here, we show that phosphorylation of PCNA on tyrosine 211 (pY211-PCNA) regulates DNA metabolism and tumor microenvironment. Abrogation of pY211-PCNA blocks fork processivity, resulting in biogenesis of single-stranded DNA (ssDNA) through a MRE11-dependent mechanism. The cytosolic ssDNA subsequently induces inflammatory cytokines through a cyclic GMP-AMP synthetase (cGAS)-dependent cascade, triggering an anti-tumor immunity by natural killer (NK) cells to suppress distant metastasis. Expression of pY211-PCNA is inversely correlated with cytosolic ssDNA and associated with poor survival in patients with cancer. Our results pave the way to biomarkers and therapies exploiting immune responsiveness to target metastatic cancer.

Abstract Purpose The dosimetric leaf gap (DLG) and multileaf collimator (MLC) transmission are two important systematic parameters used to model the rounded MLC leaf ends effect when commissioning an Eclipse treatment planning system (TPS). Determining the optimal DLG is a time consuming process. This study develops a simple and reliable method for determining the DLG using the cross-field dose width. Methods and materials A Varian TrueBeam linac with 6 MV, 10 MV, 6 MV flattening filter free (FFF) and 10 MV FFF photon beams and equipped with the 120 Millennium MLC and the Eclipse™ TPS was used in this study. Integral sliding fields and static slit MLC field doses with different gap widths were measured with an ionization chamber and GAFCHROMIC EBT3 films, respectively. Measurements were performed for different beam energies and at depths of 5 and 10 cm. DLGs were derived from a linear extrapolation to zero dose and intercepting at the gap width axis. In the ion chamber measurements method, the average MLC leaf transmission to the gap reading for each gap (R gT ) were calculated with nominal and cross-field dose widths, respectively. The cross-field dose widths were determined according to the dose profile measured with EBT3 films. Additionally, the optimal DLG values were determined using plan dose measurements, as the value that produced the closest agreement between the planned and measured doses. DLGs derived from the nominal and cross-field dose width, the film measurements, and the optimal process, were obtained and compared. Results The DLG values are insensitive to the variations in depth (within 0.07 mm). DLGs derived from nominal gap widths showed a significantly lower values (with difference about 0.5 mm) than that from cross-field dose widths and from film measurements and from plan optimal values. The method in deriving DLGs by correcting the nominal gap widths to the cross-field dose widths has shown good agreements to the plan optimal values (with difference within 0.21 mm). Conclusions The DLG values derived from the cross-field dose width method were consistent with the values derived from film measurements and from the plan optimal process. A simple and reliable method to determine DLG for rounded leaf-end MLC systems was established. This method provides a referable DLG value required during TPS commissioning.