Additional Radiation Research Articles

PD-1 Inhibitors and Chemotherapy Combined with or without Radiotherapy for Patients with Oligometastatic Esophageal Cancer

Oligometastatic esophageal cancer (OMEC) is an intermediate state between local advanced and widespread metastatic disease, which is associated with better prognosis compared to poly-metastatic esophageal cancer (EC). The previous studies demonstrated the survival benefit from local radiotherapy for OMEC patients. But the data of PD-1 inhibitors combined with radiotherapy for OMEC is still scarce. The purpose of the present study was to determine the efficacy and safety of PD-1 inhibitors plus radiotherapy in OMEC. OMEC was defined as "up to five measurable metastatic lesions and up to three organs involved". Patients with OMEC receiving PD-1 inhibitors plus chemotherapy in a single center were retrospectively analyzed in this study. They were dichotomized according to whether or not they had received radiotherapy. The efficacy and safety of immunochemotherapy combined with radiotherapy (RT group) and immunochemotherapy alone (NRT group) were investigated. A total of 226 patients were included; 108 patients received PD-1 inhibitors plus chemotherapy and radiotherapy, while other 118 patients were treated with immunochemotherapy alone. Baseline characteristics were well balanced between the groups. The overall response rate (ORR) was 58.3% in the RT group and 41.5% in the NRT group (P = 0.012), respectively. The median PFS was 13.5 months (95% CI, 10.0-17.1) for the RT group and 8.8 months (95% CI, 9.2-12.0) for the NRT group (P = 0.000). The addition of radiotherapy was the major prognostic factor for PFS (hazard ratio, 0.56; 95% CI, 0.406-0.761; P = 0.000) by univariate Cox regression analysis. Patients were well-tolerated, and the overall incidence of adverse events was similar between the RT group and NRT group. In addition, the incidence of treatment-related pneumonitis did not differ between the two groups. Grade 3-5 pneumonitis was observed in 3.7% and 5.1% of patients in the RT and NRT groups, respectively. The additional of radiotherapy to PD-1 inhibitors and chemotherapy improved PFS of patients with OMEC and showed acceptable toxicity. Further prospective studies investigating the combination of immunochemotherapy and radiotherapy are warranted.

Impact of War on Radiotherapy in Ukraine

The full-scale Russian invasion of Ukraine on February 24th, 2022 brought the largest humanitarian disaster to the heart of Europe since the World War II. Ukraine has lost tens of thousands of civilian lives, with approximately a third of the population displaced. The Russian army is deliberately damaging and destroying hospitals and clinics. This study describes the impact of the full-scale Russian invasion on the radiation therapy (RT) services in Ukraine. An annual survey was conducted by Grigoriev Institute for Medical Radiology, Kharkiv for the IAEA DIRAC database. The survey was sent to 41 RT centers in Ukraine requesting information on equipment, staffing, and patient volume. Due to the war conditions the data provided in the survey is limited. The information on operation of RT centers during the war collected by a Ukrainian Association of Medical Physicists representative is reported here as well. After the initial Russian invasion of Ukraine in 2014 and occupation of Crimea and parts of Donbas, Ukraine lost access to 7 RT centers with 18 external beam radiotherapy (EBRT) machines (17% of total). Just before the full-scale invasion in 2022, there were a total of 44 Co-60 machines (57%) and 33 linear accelerators (43%) in the unoccupied territories. As a result of the full-scale invasion of Ukraine in 2022, almost all RT centers suspended operation in the first weeks of war. The most challenging period for RT in Ukraine was in March when Kyiv (where 20 EBRT machines are located) was partially surrounded by the occupiers. The situation improved after Ukrainians liberated approximately half of total occupied territory. Currently, 2 additional RT centers are under occupation; 3 RT centers sustained heavy shelling and equipment damage. The response rate to the survey was 63%. Compared to 2021 data, in 2022, the number of radiation oncologists decreased by 7.8%, medical physicists by 7.3%, and therapists by 10.0%. The workload in the RT centers close to the combat zone almost halved, while increasing by 10 - 60% in the western and central Ukraine. The total number of patients treated with EBRT decreased by 11% and brachytherapy by 21%. Age of the RT equipment in Ukraine is shown in Table 1. Despite the ongoing war, Ukrainian cancer centers installed 3 new linear accelerators, with 14 linear accelerators pending installation. Radiotherapy in Ukraine sustained significant damages since the 2014 Russian invasion, which was exacerbated further by the full-scale invasion in 2022. To support the vitality and absorptive capacity of RT services in Ukraine, the democratic world can help by donating equipment, hardware, software, and participating in training of Ukrainian RT professionals as they transition to modern and high-quality RT care for Ukrainian cancer patients.

Outcomes of Brain Metastases with Suspicious Imaging Undergoing Resection to Evaluate for Radionecrosis vs. Tumor Progression

In patients treated with stereotactic radiosurgery (SRS) for brain metastases, radiographic changes on surveillance imaging may result from treatment effect/radionecrosis (RN) or tumor progression. Distinguishing between these processes is critical to appropriate management. We report long-term outcomes for a cohort of patients who demonstrated radiographic progression on serial imaging after initial radiation and ultimately underwent resection to inform further management. A retrospective chart review identified 76 patients with an associated 82 brain lesions between 2009 and 2022 that were initially treated with SRS, then demonstrated suspicious imaging changes developing through at least two scan time points that led to pathologic confirmation of either tumor or RN. We report clinical outcomes and details of further treatments. Of the 82 lesions, 55 (67.1%) were found to be pathologically-confirmed viable tumor and were treated with repeat radiation and 27 (32.9%) were found to be strictly RN and conservatively managed. Over half of the lesions (14/27) ultimately found to be radionecrotic required use of steroids pre-operatively due to neurologic symptoms. Among the 27 that were found to be RN, the most common histology was melanoma (33.3%, n = 9). The most common dose fractionation regimen was 20 Gy in 1 fx (n = 11, 40.7%; range: 16-20 Gy x 1Fx), and the median BED (10) was 50.4 Gy (IQR 41.6 - 50 Gy). None of these lesions required further intervention with median post-surgery follow up of 24.4 months (range 1-104 months). There were 55 instances (in 51 patients) of pathologically-confirmed recurrent/progressive tumor who were consequently treated with repeat radiation with either Cs-131 brachytherapy (12 (21.8%)) or SRS (43 (78.2%)). The most common histology was NSCLC (37.2%, n = 19). The most common fractionation for repeat irradiation with SRS was 8 Gy x 3 fx (n = 15, 27.3%), followed by 5 Gy x 5 fx (n = 10, 18.2%), and 4 Gy x 5 fx (n = 8, 14.6%). Four individuals each had two lesions that were re-irradiated for local recurrence. Among patients treated with re-irradiation, the median follow-up to local failure was 15.2 months (95% CI 7.3-26.6 months). Radionecrosis was confirmed on pathology in 4/55 (7.2%) of lesions. The median follow-up from date of SRS2 to local failure was 14.1 months (95% CI 7.6-24.3 months). The 2-yr local control rate was 74.8% (95% CI 61.7-90.7%). We recommend cautious monitoring of possible progression after radiosurgery, with consideration of resection for continuous progression, as a significant proportion of radiographic progression are ultimately pure RN. Management determined by pathology (observation for RN; additional radiation for confirmed tumor) leads to excellent control.

Selected-Lesion Stereotactic Radiosurgery in Treatment of Patients with Multiple Brain Metastases: A Single Institution Retrospective Study

Stereotactic Radiosurgery (SRS) has been increasingly used as first and subsequent-line treatments for brain metastases. While the appropriate cut-off number of lesions for SRS is still being debated nationally in patients with multiple brain metastases, some institutions use an alternate approach particularly for patients with >10-15 lesions. Selected-lesion SRS (SL-SRS) is where only a subset of lesions are chosen for initial SRS treatment leaving small and clinically inconsequential lesions for treatment using alternate or delayed treatments. This study aims to investigate the patient selection criteria, patient and tumor characteristics and analyze the outcomes in patients receiving SL-SRS for brain metastases at our institution. Clinical data from patients treated using the SL-SRS approach from 2012-2022 at our institution were retrospectively reviewed. Patients were divided into cohorts based on overall survival from time of SL-SRS treatment and indications for using SL-SRS. We compared the patient characteristics (age, histology, KPS, dsGPA), tumor characteristics (cumulative tumor volumes, tumor dose, number of brain metastases found, number of metastases treated), treatment characteristics (chemotherapy, immunotherapy, previous SRS/ radiation, previous WBRT) and the reason for decision to recommend SL-SRS across these cohort. A total of 102 patients were treated using the SL-SRS approach. Indications for using SL-SRS were immunotherapy trial (n = 40), CNS penetrating drug options available (n = 18), patient refusing WBRT (n = 6), palliative after prior WBRT/SRS (n = 28), WBRT planned to follow SRS (n = 9). 31 patients were alive at 12 months and 21 patients at 24 months. In patients surviving <12 months - the most common indications for SL-SRS were CNS palliation in the setting of progressive disease after prior WBRT or SRS. Patients in this group had median KPS< = 60 and had predominantly non-small cell carcinoma primary diagnosis. In those patients surviving >12 months - the most common indication for SL-SRS was participation in CNS-penetrant agent clinical trials without WBRT. Patients in this group were more likely to be female, had a median KPS of 90, had predominantly diagnoses of melanoma. Following the SL-SRS treatment, 14 patients required further SRS and 4 patients went on to WBRT in the >12-month survival group. No patients died of CNS progression alone. 10 patients survived 24 months without requiring further CNS radiation. In our institution, SL-SRS has predominantly been used either as palliative treatment at time of disease progression or to facilitate entry onto clinical trial with immunotherapy or potentially CNS-penetrant agents. The latter indication resulted in 47.6% patients surviving >24 month without the need for additional radiation to the CNS and therefore SL-SRS should be considered a feasible, safe and effective alternative to either WBRT or SRS treatment of all radiographically visible brain metastases.

Identifying Key Barriers for Radiation Oncology Financial Advocacy Programs

Financial toxicity is a devastating outcome for patients with cancer and can impact their treatment adherence and health outcomes. One survey reveals that most radiation oncologists are "very concerned" with the negative impact treatment-related costs have on patients, and another survey found that more than 20 percent of patients experience financial toxicity related to their radiation therapy treatment. Financial advocates within cancer programs and practices can help mitigate patients' financial toxicity by supporting shared decision-making and helping with treatment cost planning. In 2022, ACCC set out to explore how financial advocates in radiation oncology provide financial navigation to patients with cancer and address the challenges they may face. Identify barriers to financial toxicity mitigation and treatment access challenges for patients with cancer undergoing radiation therapy. ACCC worked with an expert multidisciplinary Financial Advocacy Network Advisory Committee to conduct two, semi-structured discussion sessions on financial advocacy in radiation oncology. Prepared discussion topics included challenges and opportunities in delivering financial advocacy services, financial barriers to care and strategies to mitigate financial toxicity, and processes for prior authorizations and claim denials in the radiation oncology setting. Twenty-one participants attended the first session, and 17 participants attended the second session. Participants included financial navigators and counselors, oncology social workers, nurse navigators, and cancer program or practice administrators. Three major challenges emerged from both sessions: (1) Inadequate financial assistance from independent, charitable foundations to help pay for patients' deductibles, additional radiation treatment out-of-pocket costs, and care-related transportation costs. (2) Lack of best practices to handle prior authorization and avoid denials. (3) Lack of preparedness for changes imposed by the Radiation Oncology (RO) Model, which would impact care planning. Many cancer programs and practices have implemented financial advocacy services but remain restricted in the available assistance for radiation therapy patients. Radiation therapy represents a significant component of anti-cancer treatment and addressing the lack of financial support for patients is critical to improving patients' treatment adherence and health outcomes. Payment policies must be reformed to address complex prior authorization requirements and patients would benefit from greater financial support for radiation treatment and costs of wrap-around supportive services.

Radiation-induced isomerization reaction mechanism of hydrocarbons on the surface of solid acid

This paper's goal is to investigate how petroleum's n-alkane isomerization reaction occurs on the surface of a solid nanocatalyst. In this experiment, the isomerization of aromatic-rich crude oil is being studied as a result of radiation exposure. It was discovered that sodium-rich bentonite –solid acid, from the Alpoid deposit works well as a catalyst for refining petroleum. Possible mechanisms of the radio-catalytic reaction that converts n-alkanes to branched hydrocarbons have been researched by methods of FT- IR spectroscopy and gas chromatography. The effect of acidity type of the nanostructured bentonite clay on Lewis acid cites is proposed to explain observed results. Additional radiation energy, which is mainly generated due to the nanobentonite volume, results in a more efficient aromatic- rich petroleum radiolysis process. Also, it was investigated the dynamics of dose –dependent changes in the amount of branched hydrocarbons. One of the primary objectives of this research work is increasing the efficiency of transformation of adsorbed beam energy in solid phase to the system and improvement of hydrocarbon isomerization reactions in crude oil. The results of hydrocarbon transformations are discussed in terms of the behavior of excited electrons in solids. Novel eco-friendly nanocatalyst creates new opportunities for hydrocarbons with multi- branched structures.

P11.74.A EXPERIENCE OF PREOPERATIVE GAMMA KNIFE RADIOSURGERY FOR RECURRENT BRAIN METASTASES

Abstract BACKGROUND Resection of brain metastases (BM) without additional radiation therapy yields a high local failure rate. Surgical resection of newly diagnosed BM combined with post-operative stereotactic radiosurgery (SRS) to reduce the risk of a local recurrence is an accepted and effective treatment option. Drawbacks of postoperative SRS include uncertainty in target delineation, potential delay in the administration of SRS and intraoperative risk of tumor spillage. Preoperative SRS might address these potential drawbacks. We present our experience with preoperative Gamma Knife radiosurgery (GKRS) for recurrent BM. MATERIAL AND METHODS Data of patients with recurrent BM treated with GKRS followed by surgical resection between June 2019 and June 2021 at the Elisabeth-TweeSteden Hospital Tilburg were retrospectively collected. Surgery was necessary according to the multidisciplinary team because of mass effect, a symptomatic lesion or a large tumor volume not eligible for salvage stereotactic radiosurgery. Pre-operative SRS was performed with GKRS followed by surgery within 24 hours. All patients had follow-up appointments with MRI scan as long as clinical meaningful. In case of new intracranial disease new treatment was offered if appropriate. Descriptive analyses were used to give an overview of the patient characteristics. Kaplan-Meier curves were used to analyze overall survival. RESULTS 25 patients (male 8, female 17; median age 64 years (range 20-79 years)) underwent preoperative GKRS for recurrent brain metastases. Most patients were previously treated with GKRS (76%) or SRS (24%). Most patients had non-small cell lung cancer (44%), followed by breast (12%), small cell lung cancer (12%), and melanoma (12%). The median overall survival was 18.5 months (95% CI, 4.9 to 32.1 months). Eight patients (32%) had (multiple) surgical complications, three of these patients died due to the postoperative complications. Twelve patients (48%) developed a local recurrence. The median time to local recurrence was 6.9 months (95% CI, 4.7 to 9.1months). Of the 16 patients with a subtotal resection, 10 patients developed a local recurrence, with 6 recurrences at the site of the macroscopic residual tumor. Two patients (8%) developed leptomeningeal disease at 2.8 months and 3.9 months. Two patients (8%) developed new brain metastases (distant failure) at 5.4 months and 23.8 months. CONCLUSION Pre-operative radiosurgery was well tolerated in a group of patients with recurrent BM who were eligible for surgery. Larger series are needed to perform multivariate analyses on predictors of local recurrence in order to evaluate for which patients this treatment option is best suited.

P11.45.B LOCAL RECURRENCE IN MALIGNANT PERIPHERAL NERVE SHEATH TUMORS: A MULTICENTER COHORT STUDY

Abstract BACKGROUND Malignant Peripheral Nerve Sheath Tumors (MPNSTs) are rare and aggressive malignant soft-tissue sarcomas (STS) and compromise 5-10% of STS. About 40% of MPNST cases are associated with neurofibromatosis type 1 (NF1). High-grade MPNSTs have a high probability rate of a local recurrence (LR). Risk factors vary in current literature due to its rarity, as does the optimal treatment for LRs. Factors include the role of radiotherapy, surgical margins and NF1. This study investigated both gaps in knowledge. MATERIAL AND METHODS Surgically treated primary MPNSTs between 1988 to 2019 in the MONACO multicenter cohort were included. Multivariate Cox regression analyses were performed to identify factors associated with LR and overall survival (OS) after a LR diagnosis. Treatment of LR was evaluated. RESULTS A total of 507 patients were included in this analysis, of which 142 developed a first LR. A high-grade (HR 3.40; 95% CI, 1.32-8.70) , microscopically positive margins (R1) (HR 3.6; 95% CI, 2.16-6.00), and tumor size (HR 2.14; 95% CI, 1.04-4.42) were independent risk factors for the development of a LR. Radiotherapy (HR 0.43; 95% CI, 0.23-0.79), on the other hand, reduced the risk. Patients with a LR had significantly worse OS. Most LRs (50.7%) were treated surgically without additional therapy. Only a small amount of patients (11.3%) received additional radiotherapy. CONCLUSION This analysis provides important insights into clinicopathologic, and treatment factors associated with a LR and outcomes in MPNST patients. NF1 is not associated with an increased risk of developing a LR1 whereas other clinical factors are.

Letter regarding "Feasibility of additional radiotherapy in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab".

Letter regarding "Feasibility of additional radiotherapy in patients with advanced hepatocellular carcinoma treated with atezolizumab plus bevacizumab".

Differential privacy preserved federated transfer learning for multi-institutional 68Ga-PET image artefact detection and disentanglement

PurposeImage artefacts continue to pose challenges in clinical molecular imaging, resulting in misdiagnoses, additional radiation doses to patients and financial costs. Mismatch and halo artefacts occur frequently in gallium-68 (68Ga)-labelled compounds whole-body PET/CT imaging. Correcting for these artefacts is not straightforward and requires algorithmic developments, given that conventional techniques have failed to address them adequately. In the current study, we employed differential privacy-preserving federated transfer learning (FTL) to manage clinical data sharing and tackle privacy issues for building centre-specific models that detect and correct artefacts present in PET images.MethodsAltogether, 1413 patients with 68Ga prostate-specific membrane antigen (PSMA)/DOTA-TATE (TOC) PET/CT scans from 3 countries, including 8 different centres, were enrolled in this study. CT-based attenuation and scatter correction (CT-ASC) was used in all centres for quantitative PET reconstruction. Prior to model training, an experienced nuclear medicine physician reviewed all images to ensure the use of high-quality, artefact-free PET images (421 patients’ images). A deep neural network (modified U2Net) was trained on 80% of the artefact-free PET images to utilize centre-based (CeBa), centralized (CeZe) and the proposed differential privacy FTL frameworks. Quantitative analysis was performed in 20% of the clean data (with no artefacts) in each centre. A panel of two nuclear medicine physicians conducted qualitative assessment of image quality, diagnostic confidence and image artefacts in 128 patients with artefacts (256 images for CT-ASC and FTL-ASC).ResultsThe three approaches investigated in this study for 68Ga-PET imaging (CeBa, CeZe and FTL) resulted in a mean absolute error (MAE) of 0.42 ± 0.21 (CI 95%: 0.38 to 0.47), 0.32 ± 0.23 (CI 95%: 0.27 to 0.37) and 0.28 ± 0.15 (CI 95%: 0.25 to 0.31), respectively. Statistical analysis using the Wilcoxon test revealed significant differences between the three approaches, with FTL outperforming CeBa and CeZe (p-value < 0.05) in the clean test set. The qualitative assessment demonstrated that FTL-ASC significantly improved image quality and diagnostic confidence and decreased image artefacts, compared to CT-ASC in 68Ga-PET imaging. In addition, mismatch and halo artefacts were successfully detected and disentangled in the chest, abdomen and pelvic regions in 68Ga-PET imaging.ConclusionThe proposed approach benefits from using large datasets from multiple centres while preserving patient privacy. Qualitative assessment by nuclear medicine physicians showed that the proposed model correctly addressed two main challenging artefacts in 68Ga-PET imaging. This technique could be integrated in the clinic for 68Ga-PET imaging artefact detection and disentanglement using multicentric heterogeneous datasets.

Accuracy of Anatomical Depictions in Cone Beam Computed Tomography (CBCT)-Reconstructed Panoramic Projections Compared to Conventional Panoramic Radiographs: A Clinical Risk-Benefit Analysis.

Two-dimensional (2D) radiographs are the standard of care for diagnosis and treatment planning in the day-to-day practice of dentistry. With the growing popularity of cone beam computed tomography (CBCT), it is now becoming the standard of care in many areas of general dentistry due to its ability to create non-linear projections from volumetric data. The CBCT-generated non-orthogonal radiographs can serve as easy-to-use 2D and three-dimensional (3D) diagnostic tools and offer a similar experience for diagnosis as conventional 2D images. The aim of this study is to compare the accuracy of conventional radiographs and CBCT-generated projections to identify relevant anatomic landmarks and their associated variants. Thirty-two patients referred to the University of Connecticut School of Dental Medicine's Advanced Imaging Center were selected for this retrospective analysis. Nineteen anatomical landmarks were retrospectively assessed on conventional panoramic and CBCT scans generated panoramic radiographs using two different digital imaging and communications in medicine viewers. A total of 1,216 anatomical landmarks were evaluated by two oral and maxillofacial radiologists to assess the accuracy and consistency of the depiction of radiographic anatomy. There was a very good agreement between the two evaluators with a Cohen's kappa value of 0.934. McNemar change test concluded that the anatomical assessment values compared between conventional panoramic and CBCT-generated panoramic radiographs are similar. This study showed that CBCT-generated panoramic images are comparable to conventional panoramic radiographs in identifying anatomical landmarks typically evaluated using a conventional panoramic projection. In addition, they have the added advantage of having 3D information in the acquired volume to better evaluate the area of interest. In clinical situations where a mid- to large-volume CBCT scan is available, a simulated panoramic image can be generated using the CBCT volume, leaving exposure of the patient to the additional radiation of a panoramic image unnecessary.

Chiral exceptional point and coherent suppression of backscattering in silicon microring with low loss Mie scatterer

Non-Hermitian systems with their spectral degeneracies known as exceptional points (EPs) have been explored for lasing, controlling light transport, and enhancing a sensor’s response. A ring resonator can be brought to an EP by controlling the coupling between its frequency degenerate clockwise and counterclockwise traveling modes. This has been typically achieved by introducing two or more nanotips into the resonator’s mode volume. While this method provides a route to study EP physics, the basic understanding of how the nanotips’ shape and size symmetry impact the system’s non-Hermicity is missing, along with additional loss from both in-plane and out-of-plane scattering. The limited resonance stability poses a challenge for leveraging EP effects for switches or modulators, which requires stable cavity resonance and fixed laser-cavity detuning. Here we use lithographically defined asymmetric and symmetric Mie scatterers, which enable subwavelength control of wave transmission and reflections without deflecting to additional radiation channels. We show that those pre-defined Mie scatterers can bring the system to an EP without post tuning, as well as enable chiral light transport within the resonator. Counterintuitively, the Mie scatterer results in enhanced quality factor measured on the transmission port, through coherently suppressing the backscattering from the waveguide surface roughness. The proposed device platform enables pre-defined chiral light propagation and backscattering-free resonances, needed for various applications such as frequency combs, solitons, sensing, and other nonlinear optical processes such as photon blockade, and regenerative oscillators.Graphical

Fat quantification of the rotator cuff muscles using CT histogram analysis in comparison with Dixon MRI sequence.

To quantify the proportion of fat within the rotator cuff muscles using CT histogram analysis (HA) and to compare fat fraction (FF) values obtained from CT and T2*-corrected 6-echo three-dimensional gradient-echo Dixon sequences. Twenty-six patients who underwent both shoulder CT and MRI were enrolled. The FF of rotator cuff muscles was measured on FF maps of the Dixon technique. Using CT, the FF values were obtained in two ways: 1) CT mean Hounsfield Unit (HU) measurement-based fat quantification using subcutaneous fat and the teres major muscle as internal standards; and 2) CT HA-based fat quantification in which pixels from -190 to -30 HU were arbitrarily classified as fat, and those from -30 to 150 HU as muscle. Afterward, the relationship between FF values from MRI (FF-MR), CT mean HU-based analysis (FF-HU), and CT HA (FF-HA) was assessed. There were strong positive correlations (p < 0.001) between FF-MR and FF-HA, which were higher when compared with FF-HU (r = 0.90 vs. 0.77 for total). For a total of 104 rotator cuff muscles, the intraclass correlation between FF-MR and FF-HA was excellent (ICC, 0.90), which was higher than that between FF-MR and FF-HU (ICC, 0.76). The ICCs showed excellent interobserver agreement between FF-MR, FF-HU, and FF-HA (ICCs, 0.93-0.96). Fat quantification within the rotator cuff muscles using CT HA is both feasible and reliable. CT HA provides reliable quantification of intramuscular fat and has strengths regarding its retrospective applicability to conventional CT studies without additional radiation dose to subjecting patients.

Randomized Phase III Study Comparing Neoadjuvant Chemotherapy Followed by Surgery Versus Chemoradiation in Stage IB2-IIB Cervical Cancer: EORTC-55994.

This multicenter trial by the European Organisation for Research and Treatment of Cancer Gynecological Cancer Group was motivated by conflicting evidence on the value of neoadjuvant chemotherapy before surgery compared with concomitant chemoradiotherapy (CCRT) in stage IB2-IIB cervical carcinoma. Between May 2002 and January 2014, 626 patients with International Federation of Gynecology and Obstetrics stage IB2-IIb were randomly assigned between neoadjuvant chemotherapy followed by surgery (NACT-S; n = 314) and standard CCRT (n = 312). The primary end point was 5-year overall survival (OS) rate. Secondary end points were progression-free survival, OS, toxicity, and health-related quality of life (HRQOL). After a median follow-up of 8.7 years, 198 patients (31.6%) died. Age, stage, and cell type were balanced in both arms. Protocol treatment was completed in 223 of 314 (71%) patients in NACT-S and 257 of 312(82%) in CCRT arms. Main reasons for incomplete protocol treatment were toxicity (30 of 314; 9.6%) and progressive disease (21 of 314; 6.7%) in the NACT-S arm and toxicity (23 of 312; 7.4%) and patient refusal (13 of 312; 4.2%) in the CCRT arm. Additional radiotherapy after completed NACT-S was given to 107 patients (48%), and additional surgery to 20 patients (8%) after completed CCRT. Short-term adverse events (AEs) ≥grade 3 occurred more frequently with NACT-S (41% v 23%), and long-term AEs ≥grade 3 more often with CCRT (21% v 15%). The 5-year OS was not significantly different between NACT-S (72%; 95% CI, 66 to 77) and CCRT (76%; 95% CI, 70 to 80). This trial failed to demonstrate superiority in favor of the NACT-S arm but resulted in acceptable morbidity and HRQOL in both arms.

SN 2018gj: A Short Plateau Type II Supernova with Persistent Blueshifted Ha Emission

We present an extensive, panchromatic photometric (UV, optical, and near-IR) and low-resolution optical spectroscopic coverage of a Type IIP supernova SN 2018gj that occurred on the outskirts of the host galaxy NGC 6217. From the V-band light curve, we estimate the plateau length to be ∼ 70 ± 2 days, placing it among the very few well-sampled short plateau supernovae (SNe). With V-band peak absolute magnitude M V ≤ −17.0 ± 0.1 mag, it falls in the middle of the luminosity distribution of the Type II SNe. The color evolution is typical to other Type II SNe except for an early elbow-like feature in the evolution of V − R color owing to its early transition from the plateau to the nebular phase. Using the expanding photospheric method, we present an independent estimate of the distance to SN 2018gj. We report the spectral evolution to be typical of a Type II SNe. However, we see a persistent blueshift in emission lines until the late nebular phase, not ordinarily observed in Type II SNe. The amount of radioactive nickel (56Ni) yield in the explosion was estimated to be 0.026 ± 0.007 M ⊙. We infer from semianalytical modeling, nebular spectrum, and 1D hydrodynamical modeling that the probable progenitor was a red supergiant with a zero-age-main-sequence mass ≤13 M ⊙. In the simulated hydrodynamical model light curves, reproducing the early optical bolometric light curve required an additional radiation source, which could be the interaction with the proximal circumstellar matter.

Radiotherapy for extensive-stage small-cell lung cancer in the immunotherapy era.

Currently, chemoimmunotherapy is the first-line treatment for extensive-stage small-cell lung cancer (ES-SCLC). However, only 0.8%-2.5% of the patients presented complete response after chemoimmunotherapy. Considering that ES-SCLC is highly sensitive to radiotherapy, the addition of radiotherapy after first-line treatment for ES-SCLC could further improve local control, which may be beneficial for patients' survival. Prior studies have shown that consolidative thoracic radiotherapy (cTRT) can decrease disease progression and improve overall survival in patients with ES-SCLC who respond well to chemotherapy. However, the efficacy and safety of cTRT in the immunotherapy era remain unclear owing to a lack of prospective studies. Prophylactic cranial irradiation (PCI) has been shown to decrease brain metastasis (BM) and prolong survival in patients with limited-stage SCLC in previous reports. However, according to current guidelines, PCI is not commonly recommended for ES-SCLC. Immunotherapy has the potential to reduce the incidence of BM. Whether PCI can be replaced with regular magnetic resonance imaging surveillance for ES-SCLC in the era of immunotherapy remains controversial. Whole brain radiation therapy (WBRT) is the standard treatment for BM in SCLC patients. Stereotactic radiosurgery (SRS) has shown promise in the treatment of limited BM. Considering the potential of immunotherapy to decrease BM, it is controversial whether SRS can replace WBRT for limited BM in the immunotherapy era. Additionally, with the addition of immunotherapy, the role of palliative radiotherapy may be weakened in patients with asymptomatic metastatic lesions. However, it is still indispensable and urgent for patients with obvious symptoms of metastatic disease, such as spinal cord compression, superior vena cava syndrome, lobar obstruction, and weight-bearing metastases, which may critically damage the quality of life and prognosis. To improve the outcome of ES-SCLC, we discuss the feasibility of radiotherapy, including cTRT, PCI, WBRT/SRS, and palliative radiotherapy with immunotherapy based on existing evidence, which may offer specific prospects for further randomized trials and clinical applications.

Intraoperative ultrasound margin evaluation as a tool to reduce positive superficial margins in nipple and skin sparing mastectomy in breast cancer patients

BackgroundIntraoperative ultrasound (IOUS) guided conservative surgery has been shown to reduce rates of positive margins in breast cancer. The aim of the study is to evaluate the feasibility of using IOUS to assess superficial/anterior margins in nipple and skin sparing mastectomy (NSM/SSM) and its impact on reducing rates of positive margins. MethodsThis prospective study includes all breast cancer patients who had an indication for NSM/SSM at our Institution. Superficial margin width was measured by IOUS before surgery and the area marked on the skin. Same measurement was performed afterwards in the mastectomy specimen. Any superficial margin < 5 mm was re-excised intraoperatively following the mark on the skin. ResultsFifty-nine patients were included, 47 patients (79.7%) underwent NSM, and 12 patients (20.3%) a SSM. Of the 59 patients, 23 (38.98%) had margins ≥5 mm and 36 patients (61.02%) had margins of ≤5 mm. Of the 36 patients with superficial margins ≤5 mm, 20 had margins <2 mm, and 6 of them had intraoperative involved superficial margins in final pathology. However, after IOUS-guided re-excision, final pathology showed no involved margins. A 2 mm margin was set as the cut-off point for performing an intraoperative re-excision. IOUS guided re-excisions for intraoperative margins ≤2 mm significantly reduced the risk of close/positive margins in final pathology, p < 0.0001. ConclusionThe results showed that IOUS margin evaluation significantly reduced the rate of superficial positive margins in NSM/SSM. It is feasible and effective and may avoid challenging reoperations and/or additional radiation therapy for positive margins.

Thermally Direct Mesoscale Circulations Caused by Land Surface Roughness Anomalies

AbstractDeforestation, urbanization and construction of wind farms can change the land surface roughness, which can further influence surface heat fluxes and thus weather and climate. Land surface roughness anomalies can dynamically trigger convergence through changing mean wind speed. Here, we report a new mechanism, in which roughness anomalies cause thermally direct mesoscale circulations and anomalous precipitation. To study this mechanism, we conduct cloud‐permitting simulations over an idealized land surface with prescribed surface roughness anomalies. Anomalously high roughness increases turbulent mixing near the surface, which decreases land surface temperature and outgoing longwave radiation. The additional surface net radiation partly goes into greater sensible heat flux, which triggers mesoscale circulations driven by differential heating. As a result, precipitation over the high‐roughness anomaly is generally larger than that over the low‐roughness background. This new mechanism, not present in climate models, may be relevant to storm formation over wind farms, cities and forests.

Development of an age- and comorbidity- adjusted optimal radiotherapy utilisation rate for lung, rectal, prostate and cervical cancers

IntroductionOptimal radiotherapy utilisation (RTU) modelling estimates the proportion of people with cancer who would benefit from radiotherapy. Assessment of comorbidities is an important component of the assessment of suitability for radiotherapy in addition to chronological age and life expectancy. Comorbidities have not been considered in previous optimal RTU models. We aimed to develop an age- and comorbidity- adjusted optimal RTU model for patients with lung, rectal, prostate, and cervical cancer, and compare them to actual RTU rates, with a particular focus on those aged 80+ years, MethodsNew South Wales (NSW) Cancer Registry data (2010–2014) linked to radiotherapy data (2010–2015) and hospitalisation data (2008–2015) were used to determine the number of patients diagnosed with lung, rectal, prostate and cervical cancer. The Cancer Specific C3 ‘all sites’ comorbidity index was calculated from hospital diagnosis data for each patient to determine suitability for radiotherapy. The index was then incorporated into a tumour site-specific decision tree model. The actual RTU was also calculated using the linked datasets. Results14,696 patients were diagnosed with non-small cell lung cancer (NSCLC), 1839 with small cell lung cancer (SCLC), 5551 with rectal cancer, 30,935 with prostate cancer and 1216 with cervical cancer in New South Wales from 2010-2014. The proportion of patients aged 80+ years at cancer diagnosis was 25% (3603 patients), 15% (279 patients), 17% (943 patients), 12% (3745 patients), and 7% (88 patients) respectively.The age- and comorbidity- adjusted optimal RTU rates for patients aged 80+ years using the C3 index were 49% (NSCLC), 49% (SCLC), 43% (rectal), 51% (prostate) and 40% (cervical). The corresponding actual RTU rates for patients aged 80+ years were 25%, 32%, 27%, 16%, and 56%. ConclusionEven after adjusting for age and comorbidities, the actual radiotherapy utilisation rates were lower than optimal radiotherapy utilisation rates in patients aged 80+ years except for patients with cervical cancer. This warrants further assessment and research into reasons and solutions.

Non-ECG-gated cardiac CT angiography in acute stroke is feasible and detects sources of embolism.

A significant portion of cryptogenic stroke is hypothesized to be secondary to cardiac embolism. However, transthoracic echocardiogram is usually delayed after stroke, and more detailed cardiac imaging is not routinely done. This study aimed to determine whether non-ECG-gated cardiac CT angiography (cCTA) during hyperacute stroke would provide diagnostic quality images and act as an adjunct modality of cardiac imaging to detect sources of emboli. In this single-center prospective cohort study, modified Code Stroke imaging was implemented with a 64-slice CT scanner, where the longitudinal axis of CT angiography was extended from the carina to the diaphragm. The primary outcomes of image quality, recruitment feasibility, impact on hyperacute time metrics, and additional radiation dose were assessed. Secondary outcomes consisted of detection of high-risk cardiac sources of embolism, mediastinal or lung pathology, and impact on etiologic classification. One hundred and twenty eligible patients were enrolled, of which 105 (87.5%) had good/moderate quality images for motion artifact and 119 (99.2%) for contrast opacification. Total CT time, door-to-needle time, and door-to-groin puncture time were unchanged with the addition of cCTA. Eighty-nine patients received a final diagnosis of ischemic stroke, of which 12/89 (13.5%) had high-risk cardioembolic findings on cCTA. Incidental findings, such as pulmonary embolism (PE) (7/89, 7.9%) and malignancy (6/89, 6.7%), were observed. cCTA led to changes in management for 19/120 (15.8%) of all patients, and reclassification of stroke etiology for 8/89 (9%) of patients. Non-ECG-gated cCTA can be feasibly incorporated into Code Stroke and provide diagnostic quality images without delays in hyperacute time metrics. It can detect high-risk cardiac sources, and other findings impacting patient care. This may help reclassify a subset of cryptogenic stroke cases and improve secondary prevention.