Combined Radiation Research Articles

Hypofractionated radiation therapy combined with androgen deprivation therapy for clinically node-positive prostate cancer.

This study aimed to analyze the treatment outcomes of combined definitive radiation therapy (RT) and androgen deprivation therapy (ADT) for clinically node-positive prostate cancer. Medical records of 60 patients with clinically suspected metastatic lymph nodes on radiological examination were retrospectively analyzed. Eight patients (13.3%) were suspected to have metastatic common iliac or para-aortic lymph nodes. All patients underwent definitive RT with a dose fractionation of 70 Gy in 28 fractions. ADT was initiated 2-3 months before RT and continued for at least 2 years. Biochemical failure rate (BFR), clinical failure rate (CFR), overall survival (OS), and prostate cancer-specific survival (PCSS) were calculated, and genitourinary and gastrointestinal adverse events were recorded. The median follow-up period was 5.47 years. The 5-year BFR, CFR, OS, and PCSS rates were 19.1%, 11.3%, 89.0%, and 98.2%, respectively. The median duration of ADT was 2.30 years. BFR and CFR increased after 3 years, and 11 out of 14 biochemical failures occurred after the cessation of ADT. Grade 2 and beyond late genitourinary and gastrointestinal toxicity rates were 5.0% and 13.3%, respectively. However, only two grade 3 adverse events were reported, and no grade 4-5 adverse events were reported. Patients with non-regional lymph node metastases did not have worse BFR, CFR, or adverse event rates. This study reported the efficacy and tolerable toxicity of hypofractionated definitive RT combined with ADT for clinically node-positive prostate cancer. Additionally, selected patients with adjacent non-regional lymph node metastases might be able to undergo definitive RT combined with ADT.

EPEN-23. TARGETING TRISOMY MDM4 INDUCES CELL DEATH IN 1Q+ PFA EPENDYMOMA THROUGH REACTIVATION OF THE P53 PATHWAY

Abstract BACKGROUND Gain of chromosome 1q (1q+), gives a grave prognosis in pediatric posterior fossa group A ependymoma (PFA). The prevalence of 1q+ in newly diagnosed PFA stands at 25%, escalating to 50% upon recurrence. Conventional therapeutic modalities, such as complete resection and radiation, exhibit minimal efficacy in cases of 1q+ PFA, and the incorporation of additional chemotherapy in clinical trials has failed to yield substantial improvements. In this investigation, we delineate the trisomy-induced overexpression of the MDM4 gene on chromosome 1q as a driver of malignant progression in 1q+ PFA and a viable therapeutic target via idasanutlin, an MDM4 pathway inhibitor. METHODS We are using genetic and pharmaceutical inhibition of the MDM4/MDM2 pathway high-risk PFA 1q+ in vitro and in vivo models to test the efficacy of idasanutlin in a preclinical setting. Treatment effects are measured utilizing growth assays as well as genomic and transcriptomic analysis. RESULTS Our investigation reveals that two 1q+ in vitro models demonstrate a dose dependent sensitivity to idasanutlin compared to normal brain tissue. Upon exposure to idasnutlin, they also have an increase in p21 expression, a critical marker demonstrating reactivation of the p53 pathway, evidenced at both the gene expression and protein levels. Moreover, we found radiation synergistically enhances the efficacy of idasanutlin. Currently, we are evaluating our in vitro results with combination radiation and idasanutlin treatment in our 1q+ PFA preclinical in vivo models. CONCLUSIONS In summary, our study advocates for the exploration of small molecule inhibitors, with a primary focus on the promising idasanutlin compound, as a therapeutic avenue for addressing the challenge posed by ultra-high-risk 1q+ PFA. The compelling preclinical evidence presented herein lays the groundwork for advancing our understanding of the molecular intricacies underlying this malignancy, paving the way for novel and targeted treatment strategies.

TRLS-03. A PHASE 1/2 STUDY ASSESSING SAFETY AND PHARMACOKINETICS OF CEMIPLIMAB IN PEDIATRIC PATIENTS WITH RELAPSED OR REFRACTORY SOLID OR CENTRAL-NERVOUS-SYSTEM TUMORS AND SAFETY AND EFFICACY OF CEMIPLIMAB IN COMBINATION WITH RADIOTHERAPY IN PATIENTS WITH NEWLY DIAGNOSED DIFFUSE INTRINSIC PONTINE GLIOMA, NEWLY DIAGNOSED HIGH-GRADE GLIOMA, OR RECURRENT HIGH-GRADE GLIOMA

Abstract BACKGROUND We investigated, for the first time, combination PD-1 inhibition (cemiplimab) and radiation therapy (RT) followed by cemiplimab monotherapy in children with solid tumors, diffuse intrinsic pontine glioma (DIPG) and high-grade glioma (HGG). METHODS We conducted a multicenter study through the Pediatric Neuro-Oncology Consortium. Phase 1 established the safety/pharmacokinetics of cemiplimab monotherapy in children (<18 years) with recurrent solid and central-nervous-system (CNS) tumors. Phase 2 evaluated cemiplimab/RT in children and young adults (3-25 years) with newly diagnosed (nd) DIPG, ndHGG or recurrent HGG (rHGG). Patients with ndDIPG and ndHGG were randomized to hypofractionated RT (hfRT) or conventionally fractionated RT (cRT). Primary endpoints included overall survival at 12 months (OS12) for ndDIPG and rHGG and progression-free survival at 12 months (PFS12) for ndHGG. Correlates included quality-of-life, circulating tumor DNA (ctDNA), immunogenicity, and PD-1 pathway components. RESULTS 25 patients (solid tumors, n=8; CNS tumors, n=17) were treated in phase 1; serum drug concentrations were comparable to adults. 32 patients were treated in phase 2. OS12 was 33.3% for ndDIPG treated with cemiplimab/hfRT (n=6), 0.0% for ndDIPG with cemiplimab/cRT (n=5), and 31.3% for rHGG (n=9). PFS12 was not estimable for ndHGG treated with cemiplimab/hfRT (n=5) and 20.0% for ndHGG treated with cemiplimab/cRT (n=7). 20 patients (35.1%) had grade 3/4 treatment-related AEs (TRAEs) and 13 (22.8%) had serious TRAEs. The most frequent grade 3/4 TRAE was decreased lymphocyte count (n=4 [7.0%]). 12 patients (21.1%) demonstrated treatment-emergent pseudo-progression, 2 (3.5%) grade 3/4. The most frequent serious TRAE was pseudo-progression (n=3 [5.3%]). CONCLUSIONS Cemiplimab/RT did not demonstrate an improvement in OS (ndDIPG and rHGG) or PFS (ndHGG), leading to early stopping for futility. However, the combination was tolerable, demonstrated similar outcomes across RT schedules, and showed similar exposure in serum compared to adults. Biologic and clinical correlate analyses are underway.

EPEN-24. 5FU SENSITIVITY IS MEDIATED THROUGH TRISOMY UCK2 EXPRESSION IN 1Q+ PFA EPN

Abstract BACKGROUND Nearly all children with gain of chromosome 1q (1q+) PFA ependymoma (EPN) will die, highlighting the urgent need to develop new treatment strategies for these patients. It has recently been shown that 1q+ creates a p53 mutant-like phenotype through trisomy expression of MDM4, a repressor of p53 signaling. This same study found toxic uracil analogs could reverse trisomy MDM4 effect on p53 and this was mediated through another 1q-trisomy gene UCK2. We and other have previously identified 5-fluorouracil (5FU) as an ependymoma specific inhibitor. In this study, we present the mechanism for 5FU sensitivity. METHODS In this study we utilize 1q+ PFA in vitro models to test the efficacy of combination radiation and 5FU in a preclinical setting. We measured p53 signaling through proteomic array and qRT-PCR for p21, a p53 response gene. RESULTS 5FU enhances radiotherapy in 1q+ PFA cell lines. Specifically, 5FU increases p53 activity mediated by the extra copy of UCK2 located on chromosome 1q in 1q+ PFA. Experimental down regulation of UCK2 resulted in decreased 5FU sensitivity in 1q+ PFA cells. Though not statistically significant, we did see prolong survival and decreased tumor burden in 1q+ PFA orthotopic patient-derived xenograft models treated with focal 2Gyx5days radiation and 5FU. CONCLUSION These results are the first to identify a 1q+ specific therapy approach in PFA EPN. Existing phase 1 studies in pediatrics have already established safety and dose of 5FU, providing a rapid translation into phase 2 trials for children both up front and at recurrence for 1q+ PFA.

Outcomes for Patients With Head and Neck Sarcoma Treated Curatively With Radiation Therapy and Surgery

Soft tissue sarcomas (STSs) of the head and neck (H&N) are rare malignancies that are challenging to manage. We sought to describe the outcomes of patients treated with curative intent using combined surgery and radiation therapy (RT) for H&N STS. We performed a single-institution retrospective review of patients with nonmetastatic STS of the H&N who were treated from 1968 to 2020. The Kaplan-Meier method was used to estimate disease-specific survival (DSS) and local control (LC). Multivariable analyses (MVAs) were conducted using Cox proportional hazards model. One hundred ninety-two patients had a median follow-up of 82 months. Tumors arose in the neck (n = 50, 26%), paranasal sinuses (n = 36, 19%), or face (n = 23, 12%). Most patients were treated with postoperative RT (n = 134, 70%). Postoperative RT doses were higher (median, 60 Gy; preoperative dose, 50 Gy; P < .001). Treatment sequence was not associated with LC (preoperative RT, 78% [63%-88%]; postoperative RT, 75% [66%-82%]; P = .48). On MVA, positive/uncertain margin was the only variable associated with LC (hazard ratio [HR], 2.54; 95% CI, 1.34-4.82; P = .004). LC was significant on MVA (HR, 4.48; 95% CI, 2.62-7.67; P < .001) for DSS. Patients who received postoperative RT were less likely to experience a major wound complication (7.5% vs 22.4%; HR, 0.28; 95% CI, 0.11-0.68; P = .005). There was no difference in the rate of late toxicities between patients who received preoperative or postoperative RT. H&N STS continues to have relatively poorer LC than STS of the trunk or extremities. We found LC to be associated with DSS. Timing of RT did not impact oncologic or long-term toxicity outcomes; however, preoperative RT did increase the chance of developing a major wound complication.

Recent Advances in the Surgical Management of Radiation-Induced Fractures following Soft Tissue Sarcomas.

Background: Post-radiation fractures are a significant complication of cancer treatment, often being challenging to manage and impacting patients' quality of life. This study systematically reviews the literature on fractures in irradiated bones, focusing on risk factors, treatment modalities, and prevention strategies. Factors increasing fracture risk include exposure to high doses of radiation of at least 50 Gy, female gender, menopausal age, and periosteal stripping. Additionally further risk factors are the size of the original tumor and osteoporosis. Methods: A search of PubMed yielded 541 articles, with 4 were ultimately included in the review. These retrospective studies focused on patients undergoing Combined Limb-Sparing Surgery and Radiation Therapy for soft tissue sarcoma. Results: Results show post-radiation fractures affect approximately 4% of patients, with the femur being the most frequently affected site. Intramedullary nailing emerges as the gold standard treatment, with prosthetic replacement or megaprostheses used in the metaepiphyseal region and as salvage procedures. Non-union and infection remain formidable complications. Conclusions: This study highlights the importance of prophylactic nailing in fracture prevention and the efficacy of free vascularized fibular flaps to achieve bone union during revision surgeries. Limited case availability and patient follow-up hinder comprehensive studies, impacting treatment outcomes.

A review of type III GEJ adenocarcinoma and the importance of early detection of gastric cancer

Gastric adenocarcinoma is the most common type of gastric cancer in the United States. Multiple factors can predispose a patient to develop such a malignancy, including having a history of Helicobacter pylori infection, tobacco use, alcohol use, specific genetic mutations, and being of Asian or Hispanic descent. Surgery is currently the only curative treatment for localized disease. With metastatic disease, the rate of survival decreases significantly, and most often, the only treatment option is palliative chemotherapy with or without combination radiation therapy. In the case of a 58-year-old man diagnosed with a gastroesophageal junction type III gastric adenocarcinoma that extended into the distal esophagus, what was thought to be a resectable tumor had already invaded vital neighboring organs, therefore, we were unable to eradicate the disease from this patient.

Numerical simulation of combined convection and radiation heat transfer in a hybrid nanofluid inside an open fins cavity under a magnetic field

Numerical simulation of combined convection and radiation heat transfer in a hybrid nanofluid inside an open fins cavity under a magnetic field

Outcomes of Head and Neck Neurogenic Tumors.

Lateral neck mass managementfrequently challenges surgeons. Nerve tissue neoplasmsare an uncommon cause of such nodules. Neurogenic tumors form a tiny percentage of the head and neck neoplastic lesions. Considering the number of nerves in this area, it is surprising that such neoplasms are not more frequently seen. A retrospective study was conducted on all patients who presented to the National Cancer Institute of Cairo, Egypt, with head and neck neurogenic neoplasms. During the last 10 years at the National Cancer Institute of Egypt (2006-2015), 40 cases of neurogenic tumors of the head and neck were treated atthe head and neck unit. Patients' ages ranged from two to 78 years with a mean age of 34.7 years. Childhood neurogenic tumors accounted for nine cases (22.5%) only in this study. Male patients diagnosed with these tumors comprised 16 cases, while female patients comprised 24 cases, with a female-to-male ratio of 1.5:1. Patient presentation depends on the biological behavior of the tumor; for instance, some of them present by slowly growing painless well-circumscribed mobile swelling, and others present by rapidly growing swelling with neurological deficit. Clinical picture and imaging studies such as CT and MRI raise suspicion andmay help delineatesuch tumors, but a definitive diagnosis is obtained by tissue biopsy. Surgery is the mainstay of treatment in most head and neck neurogenic tumors, whereas adjuvant therapy is of limited benefit in some types of neurogenic tumors.The five-year survival rate was60%for the malignant group, while death was reported in six out of 15 cases (40%). Conclusion: Most neurogenic head and neck tumorsare benign.Accurate preoperative assessment and a high degree of suspicion are the initial steps in the management. Proper treatment involves complete surgical excision; however, debulking procedures have an important role. Malignant neurogenic tumorsare aggressive and are treated with combined radical surgical resection and radiation. Chemotherapy is tried for locally advanced unresectable or metastatic disease.

Laminar convective heat transfer combining buoyancy and thermal radiation of Carreau fluid within a concentric and eccentric annulus

The present study concerns a steady-state laminar combined thermal radiation and buoyancy-driven conjugate magnetohydrodynamic (MHD) natural convective flow and heat transfer inside a fully porous medium eccentric circular annulus bounded by two infinite horizontal cylinders occupied by a Carreau fluid permeated by a uniform transverse magnetic field (B0 ) and inclined by an angle (α). The convective and thermal radiation are approximated by the Boussinesq and Roseland models, respectively. The numerical integration was performed using the implicit finite volume method. The convective terms in the momentum and energy equations were Discretized using the second-order upwind method. On the other hand, the diffusive terms were Discretized using the central difference scheme. The pressure-velocity coupling was solved using the SIMPLE approach. The findings suggest a clear trend of enhancement in the heat transfer rate when the aspect ratio and annulus eccentricity increase. This pattern is more pronounced in the negative vertical eccentricities. It is worth noting that the eccentric annulus, which has an annulus aspect ratio of 1.6 and a vertical eccentricity of −0.8, offers the best performance regarding the heat transfer mechanism inside the annulus gap. The heat transfer mechanism turns out to be strongly affected by thermal radiation, Hartmann number, and magnetic field inclination angle. The increased thermal radiation parameter and the decreased flow behavior index improve the heat transfer mechanism between the Carreau fluid and the inner cylinder in the annular gap. Furthermore, the average Nusselt number increases considerably as the induced magnetic field inclines.

Arenobufagin induces cell apoptosis by modulating the cell cycle regulator claspin and the JNK pathway in nasopharyngeal carcinoma cells

ABSTRACT Background The high recurrence rate and incidence of distant metastasis of nasopharyngeal carcinoma (NPC) result in poor prognosis. It is necessary to identify natural compounds that can complement combination radiation therapy. Arenobufagin is commonly used for heart diseases and liver cancer, but its effectiveness in NPC is unclear. Study Design and Methods The effect of arenobufagin-induced apoptosis was measured by a cell viability assay, tumorigenic assay, fluorescence assay, and Western blot assay through NPC-039 and NPC-BM cell lines. The protease array, Western blot assay, and transient transfection were used to investigate the underlying mechanism of arenobufagin-induced apoptosis. An NPC xenograft model was established to explore the antitumor activity of arenobufagin in vivo. Results Our findings indicated that arenobufagin exerted cytotoxic effects on NPC cells, inhibiting proliferation through apoptosis activation. Downregulation of claspin was confirmed in arenobufagin-induced apoptosis. Combined treatment with arenobufagin and mitogen-activated protein kinase inhibitors demonstrated that arenobufagin induced NPC apoptosis through the c-Jun N-terminal kinases (JNK) pathway inhibition. Furthermore, arenobufagin suppressed NPC tumor proliferation in vivo. Conclusion Our results revealed the antitumor effect of arenobufagin in vitro and in vivo. Arenobufagin may have clinical utility in treating NPC due to its suppression of claspin and inhibition of the JNK pathway.

Hormonal Therapy and Radiation Therapy in Prostate Cancer: 5-Year Outcomes From a Trial Evaluating Combined Androgen Blockade With 5-Alpha Reductase Inhibitors as an Alternative to Gonadotropin Releasing Hormone Agonists

BackgroundWe previously reported that for men undergoing combined androgen deprivation therapy (ADT) and radiation therapy (RT) for prostate cancer, substitution of LHRH-agonists with 5-α- reductase inhibitors (5-ARIs) led to improved preservation of 6-month hormonal quality of life (hQOL). With longer term follow-up, we evaluated disease control. MethodsIn this non-randomized trial, men with unfavorable intermediate or high-risk prostate cancer, aged ≥70 years or with Charlson Comorbidity Index ≥2, were treated with RT (78-79.2 Gy in 39-44 fractions) and either oral ADT (oADT; 5-ARI with antiandrogen) or standard of care ADT (SOC; leuprolide with antiandrogen) for up to 28 months. The primary endpoint was EPIC hQOL; secondary endpoints included biochemical control and survival as well as changes in cholesterol and hemoglobin levels. ResultsBetween 2011 and 2018, 70 men were enrolled (40 in oADT; 30 in SOC). Median follow-up was 65 months [IQR 36-94]. Five-year freedom from biochemical failure for oADT and SOC was 89% versus 86%, disease free survival was 62% versus 69%, cancer-specific survival was 100% versus 96%, and overall survival was 70% versus 81% (all P>.1). Testosterone (2 mo through 3 yr) and hemoglobin levels (2 mo through 2 yr) were higher, and cholesterol levels (1 yr) were lower in the oADT groups (all P < .05). ConclusionsIn this non-randomized study, men treated with combined RT and oADT had better preservation of hQOL and comparable 5-year disease outcomes to men treated with SOC. Eugonadal testosterone with this approach may yield measurable benefits in cholesterol and hemoglobin levels.

Synchronized measurement method of burning rate and combustion temperature of a solid propellant specimen

To characterize the combustion properties of solid propellants, the synchronized measurement method of burning rate and combustion temperature is proposed combined shadow imaging and radiation imaging. Using spectroscopic and filtering imaging, shadow and radiation images of a solid propellant specimen are obtained synchronously. Burning rate is calculated by burning surface movement velocity of shadow images, and combustion temperature is calculated by radiation image thermometry. Measurement accuracies of burning rate and combustion temperature of the solid propellant specimen are validated by other independent measurement methods. On this basis, the synchronized measurements of burning rate and combustion temperature of different formulations of solid propellant specimens under different working conditions are carried out. The results show that the influence on burning rate and combustion temperature of pressure and formulas is different. Therefore, the synchronized measurement of burning rate and combustion temperature can provide more direct data support for the evaluation of solid propellant combustion performance.

Advanced mapping of inorganic treatments on porous carbonate stones by combined synchrotron radiation high lateral μXRPD and μXRF

Understanding the effects of consolidating inorganic mineral treatments on carbonate stones of cultural heritage, and on the nature and distribution of newly formed products within the matrix, poses a significant challenge in Heritage Science and Conservation Science. Existing analytical methods often fail to deliver spatial and compositional insights into the newly formed crystalline phases with the appropriate high lateral resolution. In this study, we explore the capabilities and limitations of synchrotron radiation (SR) micro-X-ray powder diffraction (μXRPD) mapping combined with micro-X-ray fluorescence (μXRF) to give insight into compounds formed following the application of ammonium oxalate (AmOx) and diammonium phosphate-based (DAP) solutions on porous carbonate stone. Ultimately, the integration of μXRPD mapping and μXRF analysis proved itself a powerful asset in providing precise qualitative and quantitative data on the newly formed phases, in the case of both calcium oxalates (CaOxs) and calcium phosphates (CaPs), and their complex stratigraphic distribution, thus opening a new route for applications to a more comprehensive study of inorganic treatments applied to carbonate substrates.

Synergistic Activity of DNA Damage Response Inhibitors in Combination with Radium-223 in Prostate Cancer.

Radium-223 (223Ra) and Lutetium-177-labelled-PSMA-617 (177Lu-PSMA) are currently the only radiopharmaceutical treatments to prolong survival for patients with metastatic-castration-resistant prostate cancer (mCRPC); however, mCRPC remains an aggressive disease. Recent clinical evidence suggests patients with mutations in DNA repair genes associated with homologous recombination have a greater clinical benefit from 223Ra. In this study, we aimed to determine the utility of combining DNA damage response (DDR) inhibitors to increase the therapeutic efficacy of X-rays, or 223Ra. Radiobiological responses were characterised by in vitro assessment of clonogenic survival, repair of double strand breaks, cell cycle distribution, and apoptosis via PARP-1 cleavage. Here, we show that DDR inhibitors increase the therapeutic efficacy of both radiation qualities examined, which is associated with greater levels of residual DNA damage. Co-treatment of ATM or PARP inhibition with 223Ra increased cell cycle arrest in the G2/M phase. In comparison, combined ATR inhibition and radiation qualities caused G2/M checkpoint abrogation. Additionally, greater levels of apoptosis were observed after the combination of DDR inhibitors with 223Ra. This study identified the ATR inhibitor as the most synergistic inhibitor for both radiation qualities, supporting further pre-clinical evaluation of DDR inhibitors in combination with 223Ra for the treatment of prostate cancer.

Purine salvage promotes treatment resistance in H3K27M-mutant diffuse midline glioma

BackgroundDiffuse midline gliomas (DMG), including diffuse intrinsic pontine gliomas (DIPGs), are a fatal form of brain cancer. These tumors often carry a driver mutation on histone H3 converting lysine 27 to methionine (H3K27M). DMG-H3K27M are characterized by altered metabolism and resistance to standard of care radiation (RT) but how the H3K27M mediates the metabolic response to radiation and consequent treatment resistance is uncertain.MethodsWe performed metabolomics on irradiated and untreated H3K27M isogenic DMG cell lines and observed an H3K27M-specific enrichment for purine synthesis pathways. We profiled the expression of purine synthesis enzymes in publicly available patient data and our models, quantified purine synthesis using stable isotope tracing, and characterized the in vitro and in vivo response to de novo and salvage purine synthesis inhibition in combination with RT.ResultsDMG-H3K27M cells activate purine metabolism in an H3K27M-specific fashion. In the absence of genotoxic treatment, H3K27M-expressing cells have higher relative activity of de novo synthesis and apparent lower activity of purine salvage demonstrated via stable isotope tracing of key metabolites in purine synthesis and by lower expression of hypoxanthine-guanine phosphoribosyltransferase (HGPRT), the rate-limiting enzyme of purine salvage into IMP and GMP. Inhibition of de novo guanylate synthesis radiosensitized DMG-H3K27M cells in vitro and in vivo. Irradiated H3K27M cells upregulated HGPRT expression and hypoxanthine-derived guanylate salvage but maintained high levels of guanine-derived salvage. Exogenous guanine supplementation decreased radiosensitization in cells treated with combination RT and de novo purine synthesis inhibition. Silencing HGPRT combined with RT markedly suppressed DMG-H3K27M tumor growth in vivo.ConclusionsOur results indicate that DMG-H3K27M cells rely on highly active purine synthesis, both from the de novo and salvage synthesis pathways. However, highly active salvage of free purine bases into mature guanylates can bypass inhibition of the de novo synthetic pathway. We conclude that inhibiting purine salvage may be a promising strategy to overcome treatment resistance in DMG-H3K27M tumors.

Combined conjugate free convection and thermal radiation in a porous inclined enclosure occupied with Cu-Al2O3 hybrid nanofluid

This study deals numerically with a steady laminar combined conjugate natural convection and thermal radiation heat transfer within an inclined porous enclosure occupied with Cu-Al2O3 /water hybrid nanofluid; the thermal conductivity and nanofluid viscosity are correlated experimentally. The centered heat sink and source are attached respectively to the upper and lower enclosure walls at a set distance of 0.5 from the sidewall and were parameterized with length values of 0.2, 0.4, 0.6, 0.8, and 1. This analysis is performed in wide ranges of enclosure inclination angles (0≤ α ≤ 180°), thermal radiation parameters (0≤ Rd ≤ 200), hybrid nanofluid volume fractions (0.1, 0.33, 0.75, 1, 2, 3, 4, and 5%), Rayleigh numbers (103≤ Ra ≤ 106), Darcy numbers (10−5≤ Da ≤ 10−2), medium porosities (0.1≤ ε ≤ 0.9), and thermal conductivity ratios (1≤ γ ≤ 10). The Nusselt number increases as the heat sink/source length decreases. This trend is even more pronounced when the length of the sink/source is reduced. Furthermore, the average Nusselt numbers for the fluid and solid matrix gradually increase as the inclination angle of the enclosure varies from 0° to 45°. However, beyond 45°, both Nusselt numbers exhibit a noticeable decrease with increasing inclination angle of the enclosure. The average Nusselt number of the fluid significantly increases with varying thermal radiation parameters. When the thermal radiation parameter ranges from 0 to 2 and 0 to 200, the average Nusselt number of the fluid increases by 192% and 7343%, respectively. The Nusselt numbers significantly improve when the porosity decreases and the thermal conductivity ratio increases. For a porosity of 0.1 and a porous thermal conductivity ratio ranging from 1 to 10, the average Nusselt number of the fluid increases by approximately 129% and 141% when the Darcy number increases from 10−5 to 10−2.

Combined sonodynamic therapy and X-ray radiation with methylene blue and gold nanoparticles coated with apigenin: Impact on MCF7 cell viability

Combined sonodynamic therapy and X-ray radiation with methylene blue and gold nanoparticles coated with apigenin: Impact on MCF7 cell viability

Psychosocial consequences of head and neck cancer symptom burden after chemoradiation: a mixed-method study.

Patients with head and neck cancer (HNC) experience significant symptom burden from combination chemotherapy and radiation (chemoradiation) that affects acute and long-term health-related quality of life (HRQOL). However, psychosocial impacts of HNC symptom burden are not well understood. This study examined psychosocial consequences of treatment-related symptom burden from the perspectives of survivors of HNC and HNC healthcare providers. This was a cross-sectional, mixed-method study conducted at an NCI-designated comprehensive cancer center. Participants (N = 33) were survivors of HNC who completed a full course of chemoradiation (n = 20) and HNC healthcare providers (n = 13). Participants completed electronic surveys and semi-structured interviews. Survivors were M = 61years old (SD = 9) and predominantly male (75%), White (90%), non-Hispanic (100%), and diagnosed with oropharynx cancer (70%). Providers were mostly female (62%), White (46%) or Asian (31%), and non-Hispanic (85%) and included physicians, registered nurses, an advanced practice nurse practitioner, a registered dietician, and a speech-language pathologist. Three qualitative themes emerged: (1) shock, shame, and self-consciousness, (2) diminished relationship satisfaction, and (3) lack of confidence at work. A subset of survivors (20%) reported clinically low social wellbeing, and more than one-third of survivors (35%) reported clinically significant fatigue, depression, anxiety, and cognitive dysfunction. Survivors of HNC and HNC providers described how treatment-related symptom burden impacts psychosocial identity processes related to body image, patient-caregiver relationships, and professional work. Results can inform the development of supportive interventions to assist survivors and caregivers with navigating the psychosocial challenges of HNC treatment and survivorship.

Value of surgery combined chemotherapy and radiation therapy in locally advanced neuroendocrine carcinoma of the cervix: a single-center retrospective cohort study

Objective: To evaluate the surgery combined chemotherapy and radiation in locally advanced neuroendocrine carcinoma of the cervix (NECC) . Methods: This is a single-center retrospective cohort study. Locally advanced NECC patients admitted to Peking Union Medical College Hospital, Chinese Acadmy of Medical Sciences from January 2011 to April 2022 were enrolled. They were divided into concurrent chemoradiotherapy group, and surgery combined with chemotherapy and radiation group. The Kaplan-Meier method was used to analyze the progression free survival (PFS), overall survival (OS), recurrence rate, and mortality rate. Results: (1) Forty-six cases were included, 22 in concurrent chemoradiotherapy group, 24 in surgery combined chemotherapy and radiation group. With 16 patients (35%, 16/46) received neoadjuvant chemotherapy (NACT), the NACT effective rate was 15/16. (2) The median follow-up time was 27.5 months (range: 10-106 months), with 26 (57%, 26/46) experienced recurrences. There were 4 (9%, 4/46) pelvic recurrences and 25 (54%, 25/46) distant recurrences, and 3 (7%, 3/46) both pelvic and distant recurrences. Compared with concurrent chemoradiotherapy group, surgery combined chemotherapy and radiation group had lower pelvic recurrence rate [14% (3/22) vs 4% (1/24); χ2=1.296, P=0.255] but without statistic difference. Both groups had similar distant recurrence rate [55% (12/22) vs 54% (13/24); χ2=0.001, P=0.979] and overall recurrence rate [59% (13/22) vs 54% (13/24); χ2=0.113, P=0.736]. (3) During the follow-up period, 22 cases (48%, 22/46) died, with 11 cases (50%, 11/22) in concurrent chemoradiotherapy group and 11 cases (46%, 11/24) in surgery combined chemotherapy and radiation group, without significant difference (χ2=0.080, P=0.777). The postoperative 3-year and 5-year OS rates were 62.3% and 36.9%. Compared with concurrent chemoradiotherapy group, the patients in surgery combined chemotherapy and radiation group showed an extended trend in PFS (17.0 vs 32.0 months) and OS (37.0 vs 50.0 months) but without statistic differences (P=0.287, P=0.125). Both groups had similar 3-year OS rate (54.2% vs 69.9%; P=0.138) and 5-year OS rate (36.1% vs 38.8%; P=0.217). Conclusions: Our study supports the multi-modality treatment strategy (including surgery, chemotherapy and radiation) as an important component in the treatment of locally advanced NECC. The combination of surgery, chemotherapy and radiation seems to have advantages in the treatment of locally advanced NECC, but needs to be confirmed by further multicenter studies.