Subsequent Radiation Research Articles

Activatable Nanoprobe with Aggregation-Induced Dual Fluorescence and Photoacoustic Signal Enhancement for Tumor Precision Imaging and Radiotherapy.

Owing to the high sensitivity and high spatial resolution, fluorescence (FL) imaging has been widely applied for visualizing biological processes. To gain insight into molecular events on deeper tissues, photoacoustic (PA) imaging with better deep-tissue imaging capability can be incorporated to provide complementary visualization and quantitative information on the pathological status. However, the development of activatable imaging probes to achieve both FL and PA signal amplification remains challenging because the enhancement of light absorption in PA imaging often caused the quenching of FL signal. Herein, we first developed a caspase-3 enzyme activatable nanoprobe of a nanogapped gold nanoparticle coated with AIE molecule INT20 and DEVD peptides (AuNNP@DEVD-INT20) for tumor FL and PA imaging and subsequent imaging-guided radiotherapy. The nanoprobe could interact with GSH and caspase-3 enzyme to liberate INT20 molecules, leading to AIE. Simultaneously, the in situ self-assembly of AuNPs was achieved through the cross-linking reaction between the sulfhydryl and the maleimide, resulting in ratiometric PA imaging in tumor. Remarkably, the nanoprobe can generate richful ROS for cancer radiotherapy under X-ray irradiation. The platform not only achieves the aggregation-induced FL and PA signal enhancement but also provides a general strategy for imaging of various biomarkers, eventually benefiting precise cancer therapy.

Global attractor for 3D Dirac equation with nonlinear point interaction

We prove global attraction to stationary orbits for 3D Dirac equation with concentrated nonlinearity. We show that each finite energy solution converges as trightarrow pm infty to the set of four-frequency “nonlinear eigenfunctions”. The global attraction is caused by nonlinear energy transfer from lower harmonics to the continuous spectrum and subsequent dispersion radiation.

Platinum prodrug nanoparticles inhibiting tumor recurrence and metastasis by concurrent chemoradiotherapy

BackgroundAlthough concurrent chemoradiotherapy (CRT), as one of the most effective antineoplastic therapies in clinic, can successfully inhibit the growth of tumor cells, a risk of developing secondary tumor is still an insurmountable barrier in clinical practice.ResultsHerein, a new platinum prodrug composed of tannic acid (TA) and Pt2+ (TA-Pt) complex film was synthesized on the surface of Fe2O3 nanoparticles (NPs) with excellent stability and biocompatibility for enhanced CRT. In this system, TA-Pt complex could respond to the tumor acidic microenvironment and damage the DNA of tumor cells. Moreover, the internal iron core not only improved the effect of subsequent radiotherapy (RT), but also disrupted the iron balance in cells, inducing intracellular ferroptosis and eliminating apoptosis-resistant cells. In vitro and vivo experimental results indicated that more than 90% of tumor cells were depleted and more than 75% of the cured tumor-bearing mice evinced no recurrence or metastasis.ConclusionsThis work offered a new idea for combining the effective chemotherapy, RT and ferroptosis therapy to enhance the curative effect of CRT and inhibit tumor recurrence and metastasis.Graphical

68Ga-Citrate PET of Healthy Men: Whole-Body Biodistribution Kinetics and Radiation Dose Estimates.

68Ga-citrate has one of the simplest chemical structures of all 68Ga-radiopharmaceuticals, and its clinical use is justified by the proven medical applications using its isotope-labeled compound 67Ga-citrate. To support broader application of 68Ga-citrate in medical diagnosis, further research is needed to gain clinical data from healthy volunteers. In this work, we studied the biodistribution of 68Ga-citrate and subsequent radiation exposure from it in healthy men. Methods: 68Ga-citrate was prepared with an acetone-based radiolabeling procedure compliant with good manufacturing practices. Six healthy men (age 41 ± 12 y, mean ± SD) underwent sequential whole-body PET/CT scans after an injection of 204 ± 8 MBq of 68Ga-citrate. Serial arterialized venous blood samples were collected during PET imaging, and the radioactivity concentration was measured with a γ-counter. Urinary voids were collected and measured. The MIRD bladder-voiding model with a 3.5-h voiding interval was used. A model using a 70-kg adult man and the MIRD schema was used to estimate absorbed doses in target organs and effective doses. Calculations were performed using OLINDA/EXM software, version 2.0. Results: Radioactivity clearance from the blood was slow, and relatively high radioactivity concentrations were observed over the whole of the 3-h measuring period. Although radioactivity excretion via urine was rather slow (biologic half-time, 69 ± 24 h), the highest decay-corrected concentrations in urinary bladder contents were measured at the 90- and 180-min time points. Moderate concentrations were also seen in kidneys, liver, and spleen. The source organs showing the largest residence times were muscle, liver, lung, and heart contents. The heart wall received the highest absorbed dose, 0.077 ± 0.008 mSv/MBq. The mean effective dose (International Commission on Radiological Protection publication 103) was 0.021 ± 0.001 mSv/MBq. Conclusion: PET imaging with 68Ga-citrate is associated with modest radiation exposure. A 200-MBq injection of 68Ga-citrate results in an effective radiation dose of 4.2 mSv, which is in the same range as other 68Ga-labeled tracers. This suggests the feasibility of clinical studies using 68Ga-citrate imaging in humans and the possibility of performing multiple scans in the same subjects across the course of a year.

Anatomical and functional outcomes of non-obstetric urogenital fistula repair.

Studies on non-obstetric urogenital fistulas (NOUGFs) provide limited information on predictive outcome factors. This study was aimed at specifying and analyzing the risk factors for long-term anatomical and functional results. A cross-sectional study of surgical repair for non-obstetric urogenital fistula was performed. From 2012 to 2020, a total of 479 patients with urogenital fistulas were treated in two tertiary centers. Patients with isolated ureteral fistulas and rectal injuries were excluded. For evaluation of the long-term results, patients with vesicovaginal and urethrovaginal fistulas with at least 12months of follow-up were identified and contacted by phone and/or examined in the clinic. The anatomical outcome was assessed by resolution of symptoms and/or clinical examination. The Urinary Distress Inventory (UDI-6) was used for the functional outcomes. Overall, 425 patients were studied (mean age was 49.8; BMI 27.5; mean fistula size 1.4cm, mean follow-up was 12months). Vesicovaginal fistula affected 73% of patients. Hysterectomy without radiation was the most common etiology (66.3%), followed by hysterectomy with subsequent radiation (16%) and pelvic radiotherapy (12.2%). The transvaginal approach was used in 54.4%, abdominal in 12.4%, transvesical in 22.4%, and a combined approach in 10.8%. The successful closure rate was 92.9% for primary cases, 71.6% for secondary cases, and 66.7% for radiation fistulas. A high risk for relapse was found for NOUGFs with ureteral involvement (RR 2.5; 95% CI 1.3-4.5; p = 0.003), radiation fistulas (RR 2.1; 95% CI 1.3-3.5, p = 0.003); and combined radiation and hysterectomy cases (RR 2.9; 95% CI 1.8-4.6; p = 0.0001). In multifactorial analysis, fistula size >3.0cm, pelvic radiation, and previous vaginal surgeries were associated with a higher risk for failure or lower urinary symptoms. Factors for successful NOUGF closure are fistula size less than 3.0cm, absence of pelvic radiation, and previous vaginal surgeries.

Adaptive radiation therapy using weekly hypofractionation for thymoma treatment: A retrospective study of 10 rabbits.

Radiation therapy (RT) is being utilized more commonly for rabbit thymomas due to high perioperative mortality rates with surgery. Median overall survival times reported for rabbit thymomas treated with a variety of RT protocols and techniques range from 6months to greater than 2 years. As thymomas are radiation-responsive tumours and may shrink rapidly after RT, adaptive radiotherapy (ART) is often warranted. The purpose of this single-institution retrospective case series was to investigate the tumour volume reduction during RT, the frequency of replanning during RT, and survival time in rabbit thymomas treated using intensity-modulated/image-guided radiation therapy (IMRT/IGRT) and a weekly hypofractionated protocol delivering a total dose of 30 Gy. Ten rabbits met the inclusion criteria from October 2014 to October 2019. The median progression-free survival was 561 days and the median overall survival was 634 days (range: 322-1118 days). The tumour volume gradually decreased with each RT fraction. On post-hoc analysis, only the first RT fraction was associated with a significant GTV reduction (of more than 50% on average, p < .001). All subsequent RT fractions did not further reduce the GTV significantly (p > .06). Hypofractionated RT using a weekly protocol of 5 fractions of 6Gy is a reasonable option to treat rabbit thymomas and replanning should be anticipated. The results of this study support the use of RT to rapidly relieve thymoma-induced dyspnoea in rabbits.

Inflation and the cosmological (not-so) constant in unimodular gravity

We propose a mechanism for generating an inflationary phase in the early universe without resorting to any type of scalar field(s). Instead, this accelerated expansion is driven by a dynamical ‘cosmological constant (CC)’ in the framework of unimodular gravity (UG). The time dependent CC can be related to an energy diffusion term that arises naturally in UG due to its restrictive diffeomorphism invariance. We derive the generic conditions required for any type of diffusion to generate a realistic inflationary epoch. Furthermore, for a given parameterization of inflation (in terms of the Hubble flow functions), we show how to construct the corresponding diffusion term in such a way that a smooth transition occurs between inflation and the subsequent radiation dominated era, hence reheating proceeds naturally. The primordial spectrum is obtained during the inflationary phase by considering inhomogeneous perturbations associated to standard hydrodynamical matter (modeled as a single ultra-relativistic fluid). We demonstrate that the resulting spectrum is equivalent to that obtained in traditional inflationary models, and is also independent of the particular form of the diffusion term. In addition, we analyze the feasibility of identifying the variable CC, responsible for the inflationary expansion, with the current observed value.

Gemcitabine Versus Docetaxel Plus Cisplatin as Induction Chemotherapy in Nasopharyngeal Carcinoma.

To compare tumor volume reduction after induction chemotherapy (IC) with gemcitabine plus cisplatin (GP) and docetaxel plus cisplatin (DP) and to evaluate the influence on subsequent radiotherapy in locoregionally advanced nasopharyngeal carcinoma (NPC). Retrospective clinical study. Patients who received GP or DP IC followed by concurrent chemoradiotherapy (CCRT) were retrospectively enrolled. Propensity score matching (PSM) was adopted to control the balance between the GP and DP groups. A total of 41 patients treated with GP and 53 patients treated with DP were enrolled. After matching, 33 sub-pairs of 66 patients were generated in the post-PSM cohort. As compared with DP, GP was superior in its gross tumor volume of the nasopharynx (GTVnx) reduction (28.88% vs. 18.73%; P=.014) but equivalent in its gross tumor volume of the lymph nodes (GTVnd) reduction (37.58% vs. 29.79%; P=.229). Univariate and multivariate analyses confirmed that the chemotherapy regimen was an independent factor associated with the reduction in GTVnx (P=.011). The GP group exhibited advantages in the dosimetric parameters of the planning target volume of high-risk volume and low-risk volume (PTV1 and PTV2), lenses, temporal lobes, and parotid glands. Univariate and multivariate analyses confirmed that chemotherapy regimen was an independent factor associated with the dosimetric parameters of PTV1, PTV2, lenses, temporal lobes, and parotid glands. GP regimen achieves a greater GTVnx reduction than DP regimen and has an advantage in the dosimetry of subsequent CCRT. 3 Laryngoscope, 132:2379-2387, 2022.

Differential molecular response in mice and human thymocytes exposed to a combined-dose radiation regime

In the quest for more effective radiation treatment options that can improve both cell killing and healthy tissue recovery, combined radiation therapies are lately in the spotlight. The molecular response to a combined radiation regime where exposure to an initial low dose (priming dose) of ionizing radiation is administered prior to a subsequent higher radiation dose (challenging dose) after a given latency period have not been thoroughly explored. In this study we report on the differential response to either a combined radiation regime or a single challenging dose both in mouse in vivo and in human ex vivo thymocytes. A differential cell cycle response including an increase in the subG1 fraction on cells exposed to the combined regime was found. Together with this, a differential protein expression profiling in several pathways including cell cycle control (ATM, TP53, p21CDKN1A), damage response (γH2AX) and cell death pathways such as apoptosis (Cleaved Caspase-3, PARP1, PKCδ and H3T45ph) and ferroptosis (xCT/GPX4) was demonstrated. This study also shows the epigenetic regulation following a combined regime that alters the expression of chromatin modifiers such as DNMTs (DNMT1, DNMT2, DNMT3A, DNMT3B, DNMT3L) and glycosylases (MBD4 and TDG). Furthermore, a study of the underlying cellular status six hours after the priming dose alone showed evidence of retained modifications on the molecular and epigenetic pathways suggesting that the priming dose infers a “radiation awareness phenotype” to the thymocytes, a sensitization key to the differential response seen after the second hit with the challenging dose. These data suggest that combined-dose radiation regimes could be more efficient at making cells respond to radiation and it would be interesting to further investigate how can these schemes be of use to potential new radiation therapies.

Abstract DEB2-1: Pro - One Week of Whole Breast RT is the New Standard of Care

Abstract “Hypofractionation should not be used unless there is a specific rationale concerning the tumor characteristics of doing so”1. These were the words of Gilbert Fletcher, M.D. Anderson Cancer Center, Texas in 1990. So what prompted this bold statement? In 1969, Frank Ellis published his manuscript proposing an isoeffect formula for hypofractionation with a total dose reduction modelled on acute skin reactions2. The Ellis isoeffect formula was intended to be carefully tested, but there was wholesale international adoption as hypofractionation seemed a perfect solution for constrained radiotherapy resources3. This was coupled with lack of quality assurance for patient positioning, field matching and dose prescription. The perfect solution was in fact the perfect storm with many patients with breast cancer suffering serious late normal tissue toxicity including brachial plexopathy. The linear-quadratic model was described subsequently and separated the distinct fractionation sensitivities of early and late-responding normal tissue4. It became clear that total dose needed to be reduced further as the dose per fraction is increased3. In the early 1980’s, John Yarnold, Royal Marsden Hospital, UK read a research manuscript by Bruce Douglas5, which had a profound effect on him and subsequent UK breast radiation research. It challenged the accepted belief that all tumours respond to radiation fractionation in the same way as early-reacting normal tissues. Yarnold hypothesised that breast cancer is as sensitive to fraction size as late-responding normal tissues and if this is so, 2Gy fractions spare tumour and normal tissues equally. Given this apparent lack of advantage, larger fractions were worth testing. At the same time, other researchers globally started to develop breast cancer hypofractionation clinical trials. This important historical background sets scene for this debate: One week of whole breast radiation is the new standard of care. It demonstrates that there is nothing “new” about breast hypofractionation and that there is certainly a “specific rationale concerning the tumor characteristics” that Fletcher called for. It also highlights our united goal as radiation/clinical oncologists to carefully evaluate and report late normal toxicity so earlier mistakes are not repeated. Breast hypofractionation represents more than 3 decades of high quality international clinical trials underpinned by robust quality assurance6-9. The research has been driven by a strong radiobiological rationale and reduced visits for patients and savings for healthcare systems is a happy consequence. During this debate, I will describe the results of the FAST-Forward trial10, address the postulated concerns and conclude why one week of radiotherapy should be the new standard of care.

Outcomes of Vesicourethral Anastomotic Stenosis and Bladder Neck Contracture With Direct Visual Internal Urethrotomy With Mitomycin-C After Prostate Cancer Treatment

ObjectiveTo examine the use of Direct Visual Internal Urethrotomy with Mitomycin-C (DVIU-MMC) for bladder neck contracture and vesicourethral anastomotic stenosis in men who have undergone treatment for prostate cancer with radical prostatectomy and/or radiation therapy. MethodsRetrospective chart review of patients at a tertiary care center who underwent DVIU-MMC for recurrent bladder neck contracture/vesicourethral anastomotic stenosis between 2012 and 2020. Patients with complete urethral obliteration, prior bladder neck reconstruction, or less than 3 months of follow-up were excluded. Patients were sorted into three groups based on prostate cancer treatment history: radical prostatectomy (RP), RP with subsequent external beam radiation therapy (RP-EBRT), and radiation therapy (RT). ResultsFifty-one patients with a median follow up of 32 months were included. Twenty-nine percent had pre-operative suprapubic tube (SPT), Foley, or required clean intermittent catheterization. Overall success after initial DVIU-MMC was 45%. In all patients with up to four procedures, cumulative overall success was 84%. There was no significant difference in relative success rates between groups. However, the interval to recurrence after initial DVIU-MMC was shortest for RP-EBRT group (P = .018). Three patients required SPT, all were in the RP-EBRT group. There was no statistical difference in recurrence after any number of procedures between patients in radiation (RP-EBRT and RT) and non-radiation (RP) groups. ConclusionThere was no significant difference in success rates between patients who had undergone RP-EBRT, RT, or RP. However, our data suggests that RP-EBRT patients experience poorer outcomes given that their interval to recurrence was more rapid and all patients requiring SPT placement were in this group.

Galectin expression detected by 68Ga-galectracer PET as a predictive biomarker of radiotherapy resistance

Hypoxia is a hallmark of solid tumors that is related to radiotherapy resistance. As galectin members, such as galectin-1 and galectin-3, are associated with tumor hypoxia, herein we aimed to investigate whether positron emission tomography (PET) imaging of galectin expression can be employed to effectively pinpoint tumor hypoxia, and to predict radiotherapy resistance. We synthesized a galectin-targeting radiotracer, designated 68Ga-galectracer, by radiolabeling a thiodigalactoside derivative. The properties of 68Ga-galectracer for PET imaging of tumor hypoxia were characterized in three tumor hypoxia mouse models. Additionally, preliminary PET/CT was performed in two patients with lung cancer to investigate the potential application of 68Ga-galectracer for clinical imaging. High-contrast imaging was achieved in the murine acute hypoxia tumor model, A549 natural hypoxia model, and sorafenib treatment-induced hypoxic 4T1 tumor model by PET using 68Ga-galectracer. In fact, 68Ga-galectracer exhibited superior hypoxia detection to that of 18F-misonidazole in the 4T1 tumors. Moreover, tumors with high galectin expression levels, as detected by 68Ga-galectracer PET, exhibited significantly lower responses to subsequent radiotherapy compared to those with low galectin expression levels. In patients with lung cancer, PET imaging using 68Ga-galectracer provided data that were complementary to that of the glucose metabolic PET radiotracer 18F-fluorodeoxyglucose. 68Ga-galectracer is a promising radiotracer for PET-based imaging of tumor hypoxia in vivo. Thus, hypoxia PET with 68Ga-galectracer could provide a noninvasive approach to proactively predict radiotherapy efficacy. Chictr.org.cn (ChiCTR2000029522). Registered 03 February 2020.

Comparison of toxicity following single versus tandem autologous transplant regimens for pediatric medulloblastoma.

Medulloblastoma outcomes have improved with craniospinal irradiation and chemotherapy, but such therapy has resulted in poor neurocognitive outcomes for young patients. Chemotherapy-only regimens with autologous transplant have been implemented with the intention of avoiding radiation. It is not yet known whether single or tandem transplantation is superior with respect to efficacy and/or safety. We performed a retrospective review of children with medulloblastoma treated at Dana-Farber Cancer Institute from 1996 to 2016 who received either single or tandem autologous transplantation after completion of induction chemotherapy. We compared safety and outcome data between the two groups. Among 23 patients, 12 received tandem transplants. Median follow-up was 6.4years (IQR=0.8-10.5). There was no statistically significant difference in 5-year EFS or OS between the single (70.7±14%, 80.2±13%) and tandem transplant groups (57.1±15%, 79.6±13%). Seven tandem transplant patients received subsequent radiation while only four required radiation in the single transplant group (p=.41). In the single transplant regimen, patients experienced longer antibiotic duration (p=.03) and LOS (p=.01) and a trend toward increased number of transfusions (p=.06). Four cases of veno-occlusive disease were reported in the single transplant group (p=.04). Outcomes were similar between regimens, but the single transplant regimen had more hepatic complications. These data suggest that tandem transplant regimens may have reduced toxicity compared to the single transplant regimen with similar outcome measures.

Adaptation of O157:H7 and non-O157 Escherichia coli strains in orange juice and subsequent resistance to UV-C radiation

This study assessed the acid-adaptation of pathogenic and non-pathogenic strains of Escherichia coli in orange juice and the microbial resistance to the subsequent UV-C radiation treatment. Nine Shiga toxin-producing E. coli (STEC) and one strain of a non-pathogenic surrogate E. coli were used in this study. Each E. coli strain was inoculated in orange juice, following pre-exposure during 0, 1, 2, and 3 h at 10 °C. Then, the inoculated juices with the ten different strains separately were exposed to 0 and 2 J/cm2 of UV-C radiation. The D value (i.e., the UV-C dose in J/cm2 required to cause a one-log reduction in the target microorganism) was calculated. Further, the resistance coefficient [RC; i.e., the ratio between the D-values for the control condition (D0h) and each pre-exposure tested time (D1h,D2h, D3h)] were determined. The results indicated that the resistance of E. coli was influenced by the pre-exposure period in the orange juice, with increased resistance to UV-C observed for periods >2 h. Furthermore, the sensitivity of cells to subsequent UV-C treatment was found to be strain-dependent. The results may allow the development of more reliable UV-C radiation processes for orange juice processing aiming the inactivation of pathogenic E. coli.

Long-Term Risk of Clinical Progression Utilizing Magnetic Resonance Imaging Findings of Locally Recurrent Prostate Cancer in Patients with Biochemical Recurrence following Radical Prostatectomy.

Our goal was to evaluate the long-term prognostic value of magnetic resonance imaging of the prostatectomy bed in patients with biochemical recurrence after radical prostatectomy for prostate cancer. Men with biochemical recurrence after radical prostatectomy who were studied by prostatectomy bed magnetic resonance imaging for suspected local recurrence were retrospectively evaluated. Locally recurrent tumors were noted and measured from imaging reports. Patients with nodal/bone lesions at the time of imaging were excluded. Kaplan-Meier and Cox regression analyses were used to assess systemic progression-free and prostate cancer-specific survival. A total of 896 men were enrolled and the imaging positive and negative groups for local recurrent tumor consisted of 441 and 455 men, respectively. On univariate analysis, preoperative prostate specific antigen (p=0.02), clinical tumor stage (p=0.006), pathological Gleason score from prostatectomy (p=0.02), subsequent salvage radiotherapy (p <0.001), biochemical recurrence to magnetic resonance imaging time interval (p <0.001), age at magnetic resonance imaging (p=0.047) and prostate specific antigen at magnetic resonance imaging (p <0.001) were significantly different between magnetic resonance imaging positive and negative groups. Patients with negative magnetic resonance imaging results had worse systemic progression-free survival rates (p=0.025) and better prostate cancer-specific survival (p=0.016) than those with recurrence. Larger lesion size significantly increased risk of prostate cancer death (hazard ratio: 1.07; p <0.001). On multivariable analysis, pathological Gleason scores ≥7 were independent prognostic factors of systemic progression (p <0.05). Prostatectomy bed magnetic resonance imaging provides long-term prognostic information for the evaluation of patients with biochemical recurrence after prostatectomy. Post-prostatectomy patients with recurrent lesions on imaging had longer progression-free survival but shorter prostate cancer-specific survival compared to those without lesions. Additionally, those with larger lesions were associated with poorer cancer-specific survival.

Is perioperative brachytherapy effective in carcinoma of the tongue?

PurposeTo analyze the results of patients treated with perioperative interstitial brachytherapy (ISBT) in tongue carcinoma (TC).Material and methodsFrom April 2009 to May 2015, 43 squamous cell carcinoma consecutive patients diagnosed with TC were treated with limited partial glossectomy and perioperative ISBT, using high-dose-rate (HDR). Twenty- seven patients were treated by brachytherapy (BT), and sixteen received BT as a complement to subsequent external beam radiotherapy (EBRT) after results of lymph node dissection. Median age was 66 years. Distribution by stage, included 10 patients stage I, 14 stage II, 10 stage III, and 9 stage IV. Eighteen patients had negative margins, nineteen margin involvement, and in six cases, the margin was < 5 mm.ResultsWith a median follow-up of 54 months, LC at 3 and 5 years was 87% and 84%, respectively. LC was 95% at five years in patients with clear margins, and 75% with involved margins. LC in N0 patients treated with BT was 83% at 5 years, and in patients N+ with posterior EBRT treatment, LC was 86%. By tumor size, we found one local relapse in 13 cases T1, in 5 of 27 patients T2 was found, and no local relapse T3 with LC of 87%, 70%, and 100% respectively at five years. Regional control (RC) was 81% at 3 and 5 years. We found a metastasis-free survival of 91% at 3- and 5-year. Twenty-three patients have died, 11 of them due to other causes, with overall survival of 56% at three years and 53% at five years.ConclusionsCombined treatment with conservative surgery and ISBT shows similar results to radical surgery or RT alone, allowing a more patient-tailored approach, with good organ function preservation and cosmetic outcomes.

A clinical nomogram for predicting tumor regression grade in esophageal squamous-cell carcinoma treated with immune neoadjuvant immunotherapy.

BackgroundThere are various treatment options for esophageal squamous cell cancer. including surgery, peri-operative chemotherapy, and radiation. More recently, neoadjuvant immunotherapy has also been shown improve outcomes. In this study, we addressed the question, “Can we predict which patients with esophageal squamous cell cancer will benefit from neoadjuvant immunotherapy?”.MethodsAll patients with thoracic esophageal squamous-cell carcinoma (T2N+M0-T3-4N0/+M0) (according to the eighth edition of the National Comprehensive Cancer Network guidelines) who underwent immune neoadjuvant immunochemotherapy with programmed cell death protein 1 (PD-1) combined with paclitaxel plus cisplatin or nedaplatin in the Affiliated Cancer Hospital of Zhengzhou University, China, between November 2019 and August 2021 were included in this study. All patients underwent surgical resection. We developed a response [tumor regression grade (TRG)] prediction model using the least absolute shrinkage and selection operator (LASSO) regression incorporating factors associated with response. The accuracy of the prediction model was then validated.ResultsWe included 79 patients who underwent neoadjuvant immunotherapy combined with chemotherapy, aged 48–78 years (62.05±6.67), including 21 males and 58 females. There were five cases of immune-related pneumonia, of which three cases were diagnosed as immune-related pneumonia during the perioperative period, and one case of immune-related thyroid dysfunction changes. After LASSO regression, the factors that were independently associated with TRG were clinical T stage before neoadjuvant therapy, clinical N stage before neoadjuvant therapy, albumin level difference from before to after neoadjuvant therapy, white blood cell (WBC) count before neoadjuvant therapy, and T stage before surgery. We constructed a prediction model, plotted the nomogram, and verified its accuracy. Its Brier score was 0.13, its calibration slope was 0.98, and its C-index was 0.90 (95% CI: 0.82–0.97).ConclusionsOur prediction model can predict the likelihood of TRG in patients with esophageal squamous cell cancer after immunotherapy combined with neoadjuvant chemotherapy. Using this prediction model, we plan to conduct a subsequent neoadjuvant radiotherapy in patients with of TRG 2–3 patients with neoadjuvant radiotherapy.

Fundamental Electromagnetic Emissions by a Weak Electron Beam in Solar Wind Plasmas with Density Fluctuations

Abstract The generation of Langmuir wave turbulence by a weak electron beam in a randomly inhomogeneous plasma and its subsequent electromagnetic radiation are studied owing to two-dimensional particle-in-cell simulations in conditions relevant to type III solar radio bursts. The essential impact of random density fluctuations of average levels of a few percents of the background plasma on the characteristics of the electromagnetic radiation at the fundamental plasma frequency ω p is shown. Not only wave nonlinear interactions but also processes of Langmuir waves’ transformations on the density fluctuations contribute to the generation of such emissions. During the beam relaxation, the amount of electromagnetic energy radiated at ω p in a plasma with density fluctuations strongly exceeds that observed when the plasma is homogeneous. The fraction of Langmuir wave energy involved in the generation of electromagnetic emissions at ω p saturates around 10−4, i.e., one order of magnitude above that reached when the plasma is uniform. Moreover, whereas harmonic emission at 2ω p dominates over fundamental emission during the time evolution in a homogeneous plasma, fundamental emission is strongly dominant when the plasma contains density fluctuations, at least during several thousands of plasma periods before being overcome by harmonic emission when the total electromagnetic energy begins to saturate.

Craniopharyngiomas: Surgery and Radiotherapy.

Taking into account the benign nature of craniopharyngiomas, the main method of treatment is the resection of the tumor. However, the tendency of these tumors to invade critical structures (such as optic pathways, the hypothalamic-pituitary system, the Willis circle vessels) often limits the possibility of a radical surgery.Craniopharyngiomas of the third ventricle represent the greatest challenge for surgery. After radical surgery, hypothalamic disorders often occur, including not only obesity but also cognitive, emotional, mental, and metabolic disturbances. Metabolic disorders associated with damage to the hypothalamus progress after surgery and lead to impaired functions of the internal organs. This process is irreversible and, in many cases, becomes the direct cause of mortality. The life expectancy of patients with the surgically affected hypothalamus is significantly shorter than in patients with preserved diencephalic function. The incidence of hypothalamic disorders after surgery can reach 40%.Even with macroscopically total resection, craniopharyngiomas can recur in 10-30% of cases, and in the presence of tumor remnants and with no further radiation treatment, the risk of recurrence significantly increases to up to 50-85% according to various studies. For this reason, the observation of patients with residual tumors after surgery is an incorrect strategy.Radiation therapy significantly improves progression-free survival (PFS), and the use of stereotactic irradiation techniques ensures conformity of irradiation of tumor remnants with a complicated shape and location (Iwata H et al., J Neurooncol 106(3):571-577, 2012; Aggarwal et al., Pituitary 16(1):26-33, 2013; Savateev et al., Zh Vopr Neirokhir Im N N Burdenko 81(3):94-106; 2017), which potentially reduces the risk of undesirable postradiation effects. Therefore, the quality of life in patients with craniopharyngiomas infiltrating the hypothalamus is significantly higher after non-radical operations with subsequent stereotactic radiation than after a total or subtotal removal.

Features of Signals from Distributed Targets of an Autodyne Pulse Radar with Linear Frequency Modulation

A mathematical model has been developed to describe the signals of an autodyne short-range radar system (SRRS) with simultaneous pulse modulation (PM) of amplitude and linear frequency modulation (LFM). The features of the formation of signals received from a distributed target in the form of an ensemble of an arbitrary number of point reflectors are considered. Calculations of signals by the proposed step method are performed for the case of two point reflectors on a location object situated at different distances from the SRRS. The distinctive properties of the signals generated when receiving the first and subsequent radiation reflected from the target are established. After sending the probing radiation, the reception of the first reflected radiation from a set of brilliant points is accompanied by the formation of a linear superposition of signals from individual reflectors. The reception of subsequent reflections causes the appearance of a combinational interaction of the signals of individual reflectors. The nature and magnitude of such interaction is determined by the magnitude of the feedback parameter of the autodyne SRRS, which depends on the values of the frequency deviation and the delay time of the reflected radiation. The results of experimental studies of the autodyne SRRS with simultaneous amplitude and LPM have been obtained using the oscillator module made on the 8-millimeter Gann diode.