Photonic Reservoir Computing for Real-Time Respiratory Motion Prediction

The application of reservoir computing (RC) is for the first time studied in a class of forecasting tasks in which signals are under random physical perturbations, meaning that the data-baring waveform distortions are versatile, and the process is not repeatable. Tumor movement caused by respiratory motion is such a problem and real-time prediction of tumor motion is required by the clinical radiotherapy. In this work, a true-time delay (TTD) respiration monitor based on photonic RC with adjustable nodes connection is developed specifically for this task. A breathing data set from a total of 76 patients with breathing speeds ranging from 3 to 20 breath per minute (BPM) are studied. A double-sliding window technology is demonstrated to enable the real-time establishment of an individually trained model for each patient and the real-time processing of live-streamed tumor position data. Motion prediction of look-ahead times of 66.6 ms, 166.6 ms and 333 ms are investigated. With a 333 ms look-ahead time, the real-time RC model achieves an average normalized mean square error (NMSE) of 0.0246, an average mean absolute error (MAE) of 0.338 mm, an average therapeutic beam exposure efficiency of 94.14% for an absolute error (AE) < 1mm and 99.89% for AE < 3mm. This study demonstrates that real-time RC is an efficient computing framework for high precision respiratory motion prediction.

A retrospective review of conventional versus hypo-fractionated pelvic radiotherapy for locally advanced cervical cancer, in limited-resource countries: The Uganda experience

Background: Cervical cancer incidence in Uganda is 54.8 per 100 000 population. We annually treat over 800 new cervical cancers (40% of the workload), which is challenging to treat such numbers in limited resources settings. From July 2011, we commenced the use of hypo-fractionated radiotherapy (HFRT) of 45 Gy/15 fraction (#) as an alternative to conventional fractionated radiotherapy (CFRT) of 50 Gy/25#, for treatment of locally advanced cervical cancer (LACC).Aim: To compare the 5-year follow-up treatment outcomes between CFRT and HFRT.Settings: The study analysed patients treated at the Uganda Cancer Institute – a limited resource institution.Methods: This was a non-randomised, retrospective study, where 414 patients’ files were reviewed according to demographic, clinical, radiotherapy fractionations and outcomes. Inclusion criteria were International Federation of Gynecology and Obstetrics stages IIB–IIIB cervical cancer cases and had completed external beam radiotherapy and intracavitary radiotherapy.Results: Squamous cell carcinomas were 93.6% and adenocarcinomas were 3.0%. The median age was 49.5 (interquartile range [IQR]: 40.0–56.0) years. Stages IIB/IIIA/IIIB were 36.2%, 8.2%, 55.6%, respectively. Human immunodeficiency virus serology was positive, negative, and unknown in 70 (16.9%), 116 (28.0%) and 228 (55.1%), respectively. Concurrent chemo-radiation was administered in 182 (44.0%) patients. Conventional fractionated radiotherapy and HFRT were 221 (53.4%) and 193 (46.6%), respectively. At 6 months, the overall response rate was 73.3% for CFRT compared with 67.6% for HFRT (p = 0.085), whilst the grades 0–1 toxicities were 94.5% and for 94.7% CFRT and HFRT, respectively (p = 0.080). At 60 months, the survival probabilities were 44.9% for CFRT and 46.6% for HFRT (p = 0.293).Conclusion: There is no significant statistical difference between CFRT and HFRT for the treatment of LACC. The HFRT could be considered for high volume limited resource settings.

VAV2 is required for DNA repair and implicated in cancer radiotherapy resistance

Radiotherapy remains the mainstay for treatment of various types of human cancer; however, the clinical efficacy is often limited by radioresistance, in which the underlying mechanism is largely unknown. Here, using esophageal squamous cell carcinoma (ESCC) as a model, we demonstrate that guanine nucleotide exchange factor 2 (VAV2), which is overexpressed in most human cancers, plays an important role in primary and secondary radioresistance. We have discovered for the first time that VAV2 is required for the Ku70/Ku80 complex formation and participates in non-homologous end joining repair of DNA damages caused by ionizing radiation. We show that VAV2 overexpression substantially upregulates signal transducer and activator of transcription 1 (STAT1) and the STAT1 inhibitor Fludarabine can significantly promote the sensitivity of radioresistant patient-derived ESCC xenografts in vivo in mice to radiotherapy. These results shed new light on the mechanism of cancer radioresistance, which may be important for improving clinical radiotherapy.

The Influence of SSO on the Optimization Result of Nasopharynx Carcinoma Plan

PurposeTo study the influence of Monaco 5.4 treatment planning system (TPS) on the dosimetry of radiotherapy for nasopharynx carcinoma (NPC) under the condition of different segment shape optimization (SSO) times.MethodsFifteen patients with T3-4N0-2M0 stage NPC were enrolled, and each case was designed with SSO of 3, 5, 7 and 10 times respectively. The dose results of the target area and the major organs at risk (OARs) were statistically analyzed by DVH statistics; moreover, the isodose lines of 70Gy, 60Gy and 54Gy were intercepted at the same plane in the transverse, coronal and sagittal views and the segment shapes were compared at the angle of 30°, 120°, 240° and 330° in beam eye view (BEV); In addition, optimization time (OT), delivery time (DT), segments# and monitor unit (MU#) were obtained and analyzed by optimization console; the plans were verified and analyzed by using ArcCheck phantom.ResultsFor target area D2, the results of the SSO7 group and the SSO10 group were similar and both better than those of SSO3 and SSO5 groups, and the D2 results of the SSO3 group were notable higher than those of the other three groups; for the major OARs, the results of the maximum dose of spinal cord, brain stem, and lens and the mean dose and V30 of parotid glands showed the same trend. It showed that SSO7 and SSO10 share similar dose results, too which are notable better than the similar dose results shared by SSO3 and SSO5; in the dose deprogram distribution of 70Gy, 60Gy and 54Gy, partial 70Gy dose spillover occurred in both groups SSO3 and SSO5 and it was more obvious in group SSO3. While there was a no significant dose spillover in group SSO7 and group SSO10; in the sub-field alignment comparison under the same angle, the alignment became more complicated and the sub-fields were smaller as the number of SSO increased; the results of segment#, MU# and plan delivery time between different SSO groups were slightly different, while the plan optimization time changed significantly. The difference between group SSO3 and group SSO10 was more than 500s; the results were compared in ArcCheck, there was no significant difference between the groups.ConclusionsThe user-defined SSO function of Monaco 5.4 TPS effectively balances the relationship between plan design efficiency and plan quality. When SSO is 7, it is better value for efficiency and quality in clinical radiotherapy for NPC.

Connexin26 Modulates the Radiosensitivity of Cutaneous Squamous Cell Carcinoma by Regulating the Activation of the MAPK/NF-κB Signaling Pathway

Previous studies have confirmed that the gap junction protein Connexin26 (Cx26) is specifically expressed in human skin tissue. Cx26 can transmit radiation-induced damage signals. However, no study has yet reported whether Cx26 expression affects the radiosensitivity of human skin squamous cancer cells or the mechanism by which this occurs. In this study, we found that human skin squamous cell carcinoma cells (A431 cells) expressed significantly more Cx26 and were more sensitive to radiation compared to normal human keratinocytes (HaCaT cells). Knockdown of Cx26 in A431 cells (A431Cx26–/–) decreased radiosensitivity relative to control cells and altered the expression of key proteins in the MAPK and NF-κB signaling pathways. These results demonstrate that Cx26 expression might play an important role in mediating radiation damage in A431 cells and could serve as a potential target for clinical radiotherapy for cutaneous squamous cell carcinoma.

Characterization of Crystalline CsPbBr3 Perovksite Dosimeters for Clinical Radiotherapy

Lead halide perovskite CsPbBr3 is a wide-gap semiconductor material potentially very attractive for next generations of real-time monitors and particle detectors in high-energy physics. Here, we present the first characterization of crystalline CsPbBr3 point dosimeters with submillimeter size, under 6 MV X-photon beams used in clinical radiotherapy. Current response of the devices proved to be promising in terms of fast rise and decay times, of the same order of the X-ray beam onset and offset ones; absence of polarization effects; reproducibility to repeated irradiations; and linearity of the collected charge as a function of the absorbed dose. Comparing the measured sensitivity with the theoretical one, a charge collection distance of about 100 μm has been evaluated, of the same order of the linear dimensions of crystallites within the samples, suggesting that recombination centers are mainly placed at grain boundaries. A much higher sensitivity per unit area measured with crystalline CsPbBr3 as compared with drop-casted ones can be explained in terms of a less disordered crystalline structure. This work opens the way to CsPbBr3 point dosimeters, with linear dimensions meeting the strict spatial resolution constraints for bidimensional dose mapping required in clinical radiotherapy.

Nano-enabled Coordination Platform of Bismuth Nitrate and Cisplatin Prodrug Potentiates Cancer Chemoradiotherapy via DNA Damage Enhancement

The combination of chemotherapy and radiotherapy (chemoradiotherapy) is a promising strategy with extensively studied and applied clinically. Meanwhile, radiosensitizers play an important role in improving clinical radiotherapy therapeutic efficacy. There...