Purpose: To investigate the dosimetric characteristics of a low energy photon intra-operative radiotherapy (IORT) system and explore its potential limitation in clinical application. Methods: A special water phantom, ...Purpose: To investigate the dosimetric characteristics of a low energy photon intra-operative radiotherapy (IORT) system and explore its potential limitation in clinical application. Methods: A special water phantom, a parallel-plate ionization chamber and an electrometer were used to measure the depth dose rate, isotropy of dose distribution in X/Y plane, dosimetry reproducibility of bare probe and spherical applicators of different size which were used in comparison with the system data. Results: The difference in depth dose rate between the measurement and system data for bare probe is -2.16% ± 1.36%, the range of the relative deviation for isotropy in the X/Y plane is between -1.9% and 2.1%. The difference in depth dose rate, transfer coefficient, isotropy in X/Y plane between the measurement and system data for the whole set of spherical applicators is -10.0% - 2.3%, -8.9% - 4.2% and -1.6% - 2.6%, respectively. Higher surface dose rate and steeper gradient depth dose are observed in smaller spherical applicators. The depth dose rate and isotropy for bare probe and spherical applicators have been shown good reproducibility. The uncertainty of measurement is associated with the positioning accuracy, energy response, noise current and correction function f’(R). Conclusions: Thorough commissioning of the low energy photon IORT system helps us better understand the dosimetry characteristics, verify the system data, obtain adequate data for clinical application and routine quality assurance. The steep gradient depth dose and limited treatment range may restrain its potential in clinical application.展开更多
Recent advancements in radiotherapy for esophageal cancer have significantly improved treatment outcomes and patient quality of life.Traditional radiotherapy techniques have been enhanced by the integration of advance...Recent advancements in radiotherapy for esophageal cancer have significantly improved treatment outcomes and patient quality of life.Traditional radiotherapy techniques have been enhanced by the integration of advanced imaging and precision targeting technologies,such as intensity-modulated radiotherapy and proton therapy,which allow for more accurate tumor targeting while minimizing damage to surrounding healthy tissues.Additionally,combining radiotherapy with immunotherapy has shown promising results,leveraging the body’s im-mune response to enhance the effectiveness of cancer treatment.Studies have also highlighted the benefits of neoadjuvant chemoradiation followed by surgical resection,which has been associated with improved overall survival rates com-pared to radiotherapy alone.These innovations are paving the way for more effe-ctive and personalized treatment strategies,offering new hope for patients with esophageal cancer.展开更多
The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the ...The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the influence of different TRT timing strategies(consolidative vs.salvage)on survival rates.We retrospectively analyzed a total of 54 patients with ES-SCLC treated between January 2019 and July 2022.Patients receiving consolidative TRT(cTRT)within three months after completion of first-line treatment were compared with those receiving salvage TRT(sTRT)after disease progression.The primary endpoints were overall survival(OS),progression-free survival(PFS),locoregional-free survival(LRFS),and distant metastasis-free survival(DMFS);the secondary endpoint included safety.The cTRT group(n=41)showed significantly longer median OS(26.6 vs.14.8 months,P=0.048),PFS(12.9 vs.3.5 months,P<0.0001),and DMFS(10.7 vs.3.4 months,P=0.0044)than the sTRT group(n=13).Multivariate analysis revealed that cTRT was an independent,favorable prognostic factor.No significant differences in OS or LRFS were observed between high-dose(≥50 Gy)and low-dose(<50 Gy)TRT.Hematologic and respiratory toxicities were the most frequently reported adverse events,with acceptable tolerability.In conclusion,cTRT after chemoimmunotherapy significantly improves survival outcomes for ES-SCLC patients,and low-dose TRT may be a suitable option.展开更多
This editorial explores the potential integration of non-Western medicine into radiotherapy for cervical cancer.While radiotherapy remains a radical treatment for cervical cancer,its associated toxicity and decline in...This editorial explores the potential integration of non-Western medicine into radiotherapy for cervical cancer.While radiotherapy remains a radical treatment for cervical cancer,its associated toxicity and decline in quality of life can significantly impact patients’lives.Currently,most treatments are supportive,with no specific treatment options available in Western medicine.Non-Western medicine,often less toxic and easier to administer,has shown promising results when used alongside radiotherapy for cervical cancer.Despite these potential benefits,challenges such as limited evidence and restricted application areas persist.While non-Western medicines may offer potential improvements in chemoradiotherapy outcomes for cervical cancer,further research is necessary to substantiate these benefits.展开更多
BACKGROUND Bone is a major site of metastasis in nasopharyngeal carcinoma(NPC).Recently,nuclear factor kappa-beta ligand(RANKL)inhibitors have garnered attention for their ability to inhibit osteoclast formation and b...BACKGROUND Bone is a major site of metastasis in nasopharyngeal carcinoma(NPC).Recently,nuclear factor kappa-beta ligand(RANKL)inhibitors have garnered attention for their ability to inhibit osteoclast formation and bone resorption,as well as their potential to modulate immune functions and thereby enhance the efficacy of programmed cell death protein 1(PD-1)inhibitor therapy.CASE SUMMARY We present a case of a patient with NPC who developed sternal stalk metastasis and multiple bone metastases with soft tissue invasion following radical chemoradiotherapy and targeted therapy.Prior to chemotherapy,the patient experienced severe bone marrow suppression and opted out of further chemotherapy sessions.However,the patient received combination therapy,including RANKL inhibitors(denosumab)alongside PD-1,radiotherapy,and granulocyte-macrophage colonystimulating factor(PRaG)therapy(NCT05435768),and achieved 16 months of progression-free survival and more than 35 months of overall survival,without encountering any grade 2 or higher treatment-related adverse events.CONCLUSION Denosumab combined with PRaG therapy could be a new therapeutic approach for the second-line treatment in patients with bone metastases.展开更多
Background: Early research describing the concept of intensity-modulated conformal radiotherapy (IMRT) was based on 7 to 9 beams to reach an adequate level of modulation. Nevertheless, its implementation demands signi...Background: Early research describing the concept of intensity-modulated conformal radiotherapy (IMRT) was based on 7 to 9 beams to reach an adequate level of modulation. Nevertheless, its implementation demands significant resources. Our objective was to compare the compliance and homogeneity of target dose distribution between simplified IMRT and 3D-CRT in patients with cervical cancer and to assess the clinical value of simplified IMRT. Materials and Methods: From 2016 to 2017, 17 patients with stage IIB - IIIC cervical cancer were treated with external beam radiotherapy using simplified IMRT (12 cases) or 3DCRT (05 cases) and brachytherapy. Prior to radiotherapy, CT scans were conducted to delineate the target volume. The clinical target volume (CTV) included the uterus, primary tumor, supravaginal portion of the cervix, paracervical tissue, common iliac, internal and external iliac lymph nodes, obturator, and pre sacral lymph nodes, and the surrounding tissues. If the lower vagina was involved, the target volume included the whole vagina. The planning target volume (PTV) included the CTV with 1 cm anteriorly and 0.5 cm in all other directions. The PTV received 95% of 45 Gy (1.8 Gy/25 fraction). Dose-volume histogram, conformity index, homogeneity index, and treatment time per fraction were compared. Results: The 3D-CRT plan was more homogeneous than the simplified IMRT plan, while the simplified IMRT plan was more conformal. The volume of small bowels that received high-dose radiation significantly increased with simplified IMRT compared to 3D-CRT. Treatment time per fraction was 6 and 13 minutes for 3D-CRT and simplified IMRT, respectively. Conclusion: The simplified IMRT treatment plan is technically and dosimetrically acceptable and an alternative to the classic 3D-CRT plan for cervical cancer. It provides better dose distribution than 3D-CRT. However, the 3D-CRT treatment plan significantly reduced the overall treatment time per fraction.展开更多
A recent study by Zhang et al developed a neural network-based predictive model for estimating doses to the uninvolved liver during stereotactic body radiation therapy(SBRT)in liver cancer.The study reported a signifi...A recent study by Zhang et al developed a neural network-based predictive model for estimating doses to the uninvolved liver during stereotactic body radiation therapy(SBRT)in liver cancer.The study reported a significant advancement in personalized radiotherapy by improving accuracy and reducing treatment-related toxicity.The model demonstrated strong predictive performance with R-values above 0.8,indicating its potential to improve treatment consistency.However,concerns arise from the small sample size and exclusion criteria,which may limit generalizability.Future studies should incorporate larger,more diverse patient cohorts,explore potential confounding factors such as tumor characteristics and delivery technique variability,and address the long-term effects of SBRT.展开更多
BACKGROUND Older patients are more likely to have a poor performance status and comor-bidities.There is a reluctance to extensively investigate and treat older patients.As elderly individuals and patients with neoplas...BACKGROUND Older patients are more likely to have a poor performance status and comor-bidities.There is a reluctance to extensively investigate and treat older patients.As elderly individuals and patients with neoplasms each increase in number,palliative treatment of older patients is expected to grow as an issue.AIM To investigated the role of palliative radiotherapy in older patients and patients who were expected to demonstrate a therapeutic effect.METHODS From February 2019 to February 2022,33 patients aged≥80 years underwent palliative radiotherapy.The prognosis in palliative care study predictor(PiPS),palliative prognostic index(PPI),and delirium-palliative prognostic score(D-PaP)models were used for prognosis prediction.D-PaP scores calculated according to the doctor's prediction of clinical prediction of survival(CPS)were excluded and then analyzed for comparison.Radiation was prescribed at a dose of 2.5-7 Gy per fraction,up to a median of 39 Gy10(range,28-75 Gy10).RESULTS The median follow-up was 2.4 months(range,0.2-27.5 months),and 28 patients(84.8%)showed subjective symptom improvements following treatment.The 2-and 6-month survival rates of all patients were 91.5%and 91.5%,respectively.According to regression analysis,the performance status index,symptom type,and radiation dose all showed no significant correlation with the treatment re-sponse.When survival was expected for>55 days in the PiPS model,the 2-month survival rate was 94.4%.For patients with PPI and D-PaP-CPS values of 0-3.9 points,the 2-month survival rates were 90.0%and 100%,respectively.For patients with a score of≥4 points,the 2-month survival rates were 37.5%and 0%,res-pectively.Core Tip:This is a retrospective study to investigate the role of palliative radiotherapy in older patients and patients who were expected to demonstrate a great therapeutic effect.The prognosis in palliative care study predictor,palliative prognostic index,and delirium-palliative prognostic score models were used for prognosis prediction.Most of patients showed subjective symptom improvements following treatment.The prognosis prediction model showed good correlation with survival.In order to increase the therapeutic effectiveness in palliative radiotherapy,it is necessary to assess a patient's exact prognosis and select appropriate patients accordingly.INTRODUCTION The incidence of cancer is high among individuals 60-69 years old and is 11 times greater among those≥65-years-old compared to those<65-years-old.For this reason,about half of all cancer cases are diagnosed in individuals aged≥70 years,and older patients account for a large portion of the total population regarding the prevalence of cancer[1].Cancer is one of the most significant diseases in older patients.About 60%of all cancer-related deaths occur in older patients aged 70 years[1,2].Moreover,cancer accounts for about one-third of the causes of death in the elderly population[1,2].When choosing a cancer treatment,both the characteristics of the cancer and the overall health status of the patient,such as their general condition and any underlying diseases,should be considered[2].Older patients have a shorter life expectancy than younger patients;moreover,they typically have many accompanying underlying diseases and have a poorer general condition.For this reason,older patients are often rejected from receiving active testing and treatment services.Therefore,even if other factors,such as the underlying disease,are the same in young and old patients,older patients typically receive less treatment due to the simple fact that they are older[3].Palliative treatment is a treatment approach that improves the pain and symptoms of a patient and their quality of life.Although palliative treatment is applicable regardless of patient age and the type and severity of their disease,most patients requiring palliative treatment are cancer patients.Palliative radiotherapy is relatively effective for cancer patients and tends to be a well-tolerated treatment.Although some studies have reported the usefulness of palliative radiotherapy in elderly patients,a large number of patients and caregivers are not receiving treatment due to fears of treatment,the risks of side effects,and doubts about treatment effectiveness[1].Since actual age is not always associated with physical ability,the determination of treatment based solely on age can be an obstacle preventing appropriate treatment opportunities.The importance of palliative care is increasing due to the recent growth of the elderly population,as well as,the increase in cancer incidence,and the changes in traditional views or perceptions,such as a growing acceptance of the pursuit of a dignified death[4].Therefore,in this study,we investigated the role of palliative radiotherapy in older patients and in patients who are expected to show a great therapeutic effect.展开更多
Background:The role of systemic tumor immune environment(STIE)is unclear in hepatocellular carcinoma(HCC).This study aimed to exam the cells in the STIE,their changes after transarterial chemoembolisation(TACE),stereo...Background:The role of systemic tumor immune environment(STIE)is unclear in hepatocellular carcinoma(HCC).This study aimed to exam the cells in the STIE,their changes after transarterial chemoembolisation(TACE),stereotactic body radiotherapy(SBRT),and immunotherapy(IO)and explore their significance in the treatment response of patients with unresectable HCC.Methods:This is a prospective biomarker study of patients with unresectable HCC.The treatment was sequential TACE,SBRT(27.5-40 Gy/5 fractions),and IO.The treatment response was assessed according to modified Re-sponse Evaluation Criteria in Solid Tumors(mRECIST)by magnetic resonance imaging(MRI)after 6 months of treatment.Longitudinal data of STIE cells was extracted from laboratory results of complete blood cell counts,in-cluding leukocytes,lymphocytes,neutrophils,monocytes,eosinophils,basophils,and platelets.Peripheral blood samples were collected at baseline and after TACE,SBRT,and IO for T-lymphocyte subtyping by flow cytometry.Generalized estimation equation was employed for longitudinal analyses.Results:A total of 35 patients with unresectable HCC were enrolled:23 patients in the exploratory cohort and 12 in the validation cohort.STIE circulating cells,especially lymphocytes,were heterogenous at baseline and changed differentially after TACE,SBRT,and IO in both cohorts.SBRT caused the greatest reduction of 0.7×10^(9)/L(95%CI:0.3×10^(9)/L-1.0×10^(9)/L,P<0.001)in lymphocytes;less reduction was associated with significantly better treatment response.The analysis of T-lymphocyte lineage revealed that the baseline levels of CD4+T cells(P=0.010),type 1 T helper(Th1)cells(P=0.007),and Th1/Th17 ratios(P=0.001)were significantly higher in responders,while regulatory T(Treg)cells(P=0.002),Th17 cells(P=0.047),and Th2/Th1 ratios(P=0.028)were significantly higher in non-responders.After treatment with TACE,SBRT and IO,T-lymphocyte lineage also changed differentially.More reductions were observed in CD25^(+)CD8^(+)T cells and CD127^(+)CD8^(+)T cells after SBRT in non-responders,while increases in natural killer T(NKT)cells after SBRT(10.4%vs.3.4%,P=0.001)and increases in the lymphocyte counts were noted during IO in responders.Conclusions:STIE cells are significant for treatment response,can be reshaped differentially after TACE,SBRT,and IO.The most significant changes of T-lymphocyte lineage are SBRT associated modulations in CD25^(+)CD8^(+)T cells,CD127^(+)CD8^(+)T cells,and NKT cells,which also have significant effects on the ultimate treatment response after TACE-SBRT-IO(ClinicalTrails.gov identifier:GCOG0001/NCT05061342).展开更多
Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focus...Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focused on investigating the anti-tumor effect of TPP-DOX in combination with radiotherapy throughout in vitro and in vivo studies.Methods:TPP-DOX was synthesized using the carbodiimide method.In vitro experiments were conducted with 4T1 cells(mouse breast cancer cell line)to assess apoptosis induction,mitochondrial targeting,reactive oxygen species(ROS)production,and mitochondrial membrane potential.The research evaluates the effects of TPP-DOX,DOX,and their combinations with radiotherapy.A nude mouse tumor heterograft model was established to investigate the synergistic effect of TPP-DOX and radiotherapy.Results:TPP-DOX was successfully synthesized and scrupulously verified.In vitro experiments showed that compared to DOX,TPP-DOX exhibited enhanced tumor cytotoxicity,improved cellular uptake in 4T1 cells,and increased apoptosis induction.Combined with radiotherapy,TPP-DOX promoted mitochondrial ROS production,reduced mitochondrial membrane potential,and amplified its anti-tumor effect.In vivo experiment confirmed that TPP-DOX combined with radiotherapy exhibited superior anti-tumor activity,promoted tumor tissue apoptosis,inhibited tumor angiogenesis,and showed a favorable in vivo safety profile.Conclusion:The study confirmed that when combined with radiotherapy,TPP-DOX promoted tumor cell apoptosis,and effectively enhanced the anti-tumor effect.In sensitive cells,TPP-DOX demonstrates comparable efficacy to DOX when combined with radiotherapy.TPP-DOX holds significant potential for a broader spectrum of applications and emerges as a valuable candidate for clinical application.These findings provide a promising and efficient therapeutic strategy for tumor treatment with improved efficacy and safety.展开更多
BACKGROUND Currently,there is limited research examining the relationship between anxiety,depression,coping styles,and illness uncertainty in patients with cervical cancer(CC)undergoing radiotherapy.Addressing this ga...BACKGROUND Currently,there is limited research examining the relationship between anxiety,depression,coping styles,and illness uncertainty in patients with cervical cancer(CC)undergoing radiotherapy.Addressing this gap could provide valuable insights and more reliable evidence for clinical practice targeting this patient population.AIM To analyze the anxiety,depression,and coping styles of patients with CC undergoing radiotherapy and explore their correlations with illness uncertainty.METHODS A total of 200 patients with CC undergoing radiotherapy at The First Affiliated Hospital of Soochow University between June 2018 and June 2022 were enrolled.Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale(HADS),comprising subscales for anxiety(HADS-A)and depression(HADS-D).Coping styles were evaluated using the Jalowiec Coping Scale(JCS-60),comprising dimensions such as confrontive,evasive,optimistic,fatalistic,emotive,palliative,supportive,and self-reliant.Illness uncertainty was measured using the Mishel Uncertainty in Illness Scale(MUIS),encompassing ambiguity,complexity,information deficit,and unpredictability.Correlations among anxiety,depression,coping styles,and illness uncertainty were analyzed.RESULTS During radiotherapy,the mean scores were 7.12±3.39 for HADS-A,6.68±3.49 for HADS-D,1.52±0.23 for JCS-60,and 93.40±7.44 for MUIS.Anxiety(HADS-A≥8)was present in 39.5%of patients,depression(HADS-D≥8)in 41.0%,and both in 14.0%.Anxiety was significantly positively correlated with ambiguity,unpredictability,and total MUIS score(P<0.05).Depression was significantly positively correlated with ambiguity,information deficit,unpredictability,and total MUIS score(P<0.05).Most patients adopted an optimistic coping style,whereas the emotive style was least utilized.Evasive,fatalistic,and emotive coping styles were significantly positively correlated with illness uncertainty,whereas the self-reliant style was significantly negatively correlated with unpredictability(P<0.05).CONCLUSION Anxiety,depression,and coping styles in patients with CC undergoing radiotherapy correlate significantly with their level of illness uncertainty.Medical staff should address patients’psychological status and coping strategies by providing targeted information to reduce negative emotions,foster adaptive coping styles,and decrease illness uncertainty.展开更多
Objective:Although the role of circular RNAs(circRNAs)in tumor progression and immune regulation is well-known,the specific circ RNA molecules that mediate immune responses after radiotherapy(RT)and the underlying mec...Objective:Although the role of circular RNAs(circRNAs)in tumor progression and immune regulation is well-known,the specific circ RNA molecules that mediate immune responses after radiotherapy(RT)and the underlying mechanisms have not been identified.Methods:Cytometry with time-of-flight(CyTOF)was used to analyze blood samples from patients with liver cancer exhibiting abscopal effects(AEs)after stereotactic body radiotherapy(SBRT)to quantify the number of dendritic cells(DCs)and CD8+T cells and interferon-beta(IFN-β)level.circTMEM56 and IFN-βlevels were measured in 76 patients with liver cancer using q PCR and ELISA.Immunohistochemistry validated circTMEM56 and CD141 staining in tissues.The interaction between circTMEM56,miR-136-5p,and STING,as well as the impact on anti-tumor immunity,was verified using circTMEM56-specific probes,dual-luciferase activity assays,proteomics analysis,and western blot analysis.Results:The role of circTMEM56 in enhancing anti-tumor immunity and response to RT in hepatocellular carcinoma(HCC)was determined.Higher circTMEM56 levels were linked to an improved RT response and better clinical outcomes in patients with HCC.circTMEM56 enhanced cGAS-STING signaling,increased the number of tumor-infiltrating CD8+T cells,and elevated the serum IFN-βlevels.Moreover,circTMEM56 administration significantly boosted the response to RT in tumors with low circTMEM56 expression.Conclusions:High circTMEM56 expression in HCC modulates the distant effects of HCC RT by activating the cGAS-STING pathway to reshape the tumor microenvironment.This study provides a new approach to improve RT efficacy for HCC.展开更多
BACKGROUND Radiation resistance limits radiotherapy efficacy in esophageal squamous cell carcinoma(ESCC).The tumor microenvironment,particularly adipocytes,plays a role in promoting cancer progression.Extracellular ve...BACKGROUND Radiation resistance limits radiotherapy efficacy in esophageal squamous cell carcinoma(ESCC).The tumor microenvironment,particularly adipocytes,plays a role in promoting cancer progression.Extracellular vesicles and microRNAs(miRNAs)regulate gene expression and hold prognostic potential for esophageal carcinoma.Elucidating radioresistance mechanisms and identifying radiosensitization targets can help enhance radiotherapy efficacy for esophageal cancer.AIM To investigate the potential role of miRNAs derived from adipocyte exosomes as prognostic markers for radiotherapy efficacy in ESCC.METHODS Free adipocytes were isolated from human thoracic adipose tissue.A co-culture model of adipocytes and ESCC cells was established to observe colony formation and cell survival post-irradiation.ESCC cell apoptosis was assessed by flow cytometry.Western Blot and immunofluorescence assays were performed to evaluate DNA damage in ESCC cells post-irradiation.Adipocyte-derived exosomes were isolated by ultracentrifugation and identified by electron microscopy.A similar set of experiments was performed on ESCC cells to analyze cell survival,apoptosis,and DNA damage post-radiation exposure.Exosomes from adipose tissue and serum exosomes from ESCC patients pre-and post-radiotherapy were subjected to high-throughput miRNA-sequencing and validated using real-time quantitative polymerase chain reaction.The correlation between potential target miRNAs and the short-term prognosis of radiotherapy in ESCC was evaluated by receiver operating characteristic curve analysis.RESULTS Co-culturing adipocytes with ESCC cells enhanced radioresistance,as evidenced by increased colony formation.Adipocyte co-culture reduced ESCC cell apoptosis and DNA damage post-radiation.Adipocyte-derived exosomes similarly conferred radioresistance in ESCC cells,decreasing apoptosis and DNA damage post-irradiation.Highthroughput miRNA-sequencing identified miR-660-5p in serum and adipose tissue exosomes.Patients with high expression of serum exosome miR-660-5p showed poor prognosis after radiotherapy.CONCLUSION Adipocyte-derived exosomal miR-660-5p is a potential biomarker for evaluating radiotherapy efficacy in ESCC.展开更多
Real-time,noninvasive programmed death-ligand 1(PD-L1)testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy.However,the util...Real-time,noninvasive programmed death-ligand 1(PD-L1)testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy.However,the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography(PET/CT)remains limited.This investigation involved the synthesis of[18F]AlF-NOTA-PCP2,which is a novel peptide-based radiolabeled tracer that targets PD-L1,and evaluated its imaging capabilities in orthotopic glioblastoma(GBM)models.Using this tracer,we could noninvasively monitor radiation-induced PD-L1 changes in GBM.[18F]AlF-NOTA-PCP2 exhibited high radiochemical purity(>95%)and stability up to 4 h after synthesis.It demonstrated specific,high-affinity binding to PD-L1 in vitro and in vivo,with a dissociation constant of 0.24 nM.PET/CT imaging,integrated with contrast-enhanced magnetic resonance imaging,revealed significant accumulation of[18F]AlF-NOTA-PCP2 in orthotopic tumors,correlating with blood-brain barrier disruption.After radiotherapy(15 Gy),[18F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51%±0.73%to 12.04%±1.43%,indicating enhanced PD-L1 expression consistent with immunohistochemistry findings.Fractionated radiation(5 Gy×3)further amplified PD-L1 upregulation(13.9%±1.54%ID/cc)compared with a single dose(11.48%±1.05%ID/cc).Taken together,[18F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.展开更多
Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantati...Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantation are the gold standard for the radical treatment of HCC.However,due to the heterogeneity and high invasiveness of HCC,the rates of local and distant recurrence are extremely high,with over 70%of patients experiencing recurrence within 5 years after treatment,significantly impacting the long-term quality of life.Therefore,researchers are exploring other treatment methods to reduce tumor recurrence and improve patient survival.To date,extensive research has concentrated on new alternative therapies,including radiotherapy(e.g.,selective internal radiotherapy),targeted drug therapy(e.g.,sorafenib and lenvatinib),and immunotherapy(e.g.,immune checkpoint inhibitors),which have played an integral role in the comprehensive treatment of HCC.This review mainly focuses on the cutting-edge advancements in these treatment methods for HCC and their potential role in reducing HCC recurrence.展开更多
BACKGROUND Definitive chemoradiotherapy is the standard treatment for unresectable,locally advanced esophageal cancer.However,radiotherapy(RT)often affects the immune system of patients.One of the possible mechanisms ...BACKGROUND Definitive chemoradiotherapy is the standard treatment for unresectable,locally advanced esophageal cancer.However,radiotherapy(RT)often affects the immune system of patients.One of the possible mechanisms of lymphopenia after RT is that a large number of circulating lymphocytes in the systemic and pulmonary circulation will be killed by more sessions of low-dose radiation.The impact of dose-volume parameters of organs at risk(OARs)on absolute lymphocyte count(ALC)and the relationship between the extent of lymphocyte count reduction and survival prognosis in patients with middle and lower thoracic esophageal squamous cell carcinoma(ESCC)both remain difficult to determine.AIM To determine the relationship between RT parameters,lymphocyte count and survival prognosis of esophageal cancer patients.METHODS The clinical data of 112 patients with stage I-III ESCC who received definitive RT were analyzed retrospectively.The ALC values before RT,weekly during RT,and within 1 month after RT were determined.Logistic regression was used to evaluate the correlation between the parameters of radiation OARs and the lowest point of the ALC.Kaplan-Meier and Cox regression analyses were used to evaluate the relationship between the lowest point of the ALC and patient survival during RT.RESULTS The median value of the ALC before treatment was 1.57×10^(9)cells/L,and 32 patients(28.6%)showed grade 4 ALC reduction during RT.The reduction in G4 ALC during RT was significantly associated with poor overall survival(OS)and progression-free survival.Multivariate analysis showed that stage III tumors(P=0.003),high heart V_(10)(P=0.046),high lung V_(5)(P=0.048),and high lung V_(20)(P=0.031)were associated with G4 ALC reduction during RT.CONCLUSION The reduction in G4 ALC is related to OS.Joint evaluation of the tumor stage and dose volume parameters has predictive value for G4 ALC reduction and OS.展开更多
Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for ...Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC).A crucial question is whether concurrent chemo-radiotherapy(CCRT)could derive additional benefits to this recent“down-staging”subgroup of NPC patients.This study aimed to interrogate clinical and radiomic features for predicting 5-year progression-free survival(PFS)of stageⅡNPC treated with RT alone or CCRT.Methods:Imaging and clinical data of 166 stageⅡNPC(eighth edition AJCC/UICC)patients were collected.Data were allocated into training,internal testing,and external testing sets.For each case,851 radiomic features were extracted and 10 clinical features were collected.Radiomic and clinical features most associated with the 5-year PFS were selected separately.A combined model was developed using multivariate logistic regression by integrating selected features and treatment option to predict 5-year PFS.Model performances were evaluated by area under the receiver operating curve(AUC),prediction accuracy,and decision curve analysis.Survival analyses including Kaplan-Meier analysis and Cox regression model were performed for further analysis.Results:Thirteen radiomic features,three clinical features,and treatment option were considered for model development.The combined model showed higher prognostic performance than using either.For the merged testing set(internal and external testing sets),AUC is 0.76(combined)vs.0.56-0.80(clinical or radiomic alone)and accuracy is 0.75(combined)vs.0.62-0.73(clinical or radiomic alone).Kaplan-Meier analysis using the combined model showed significant discrimination in PFS of the predicted low-risk and high-risk groups in the training and internal testing cohorts(P<0.05).Conclusions:Integrating with clinical and radiomic features could provide prognostic information on 5-year PFS under either treatment regimen,guiding individualized decisions of chemotherapy based on the predicted treatment outcome.展开更多
BACKGROUND The current method of cleaning and changing dressings for non-healing lumbar incisions post-radiotherapy is time-consuming and laborious,with very poor results.We here report a patient with radiation dermat...BACKGROUND The current method of cleaning and changing dressings for non-healing lumbar incisions post-radiotherapy is time-consuming and laborious,with very poor results.We here report a patient with radiation dermatitis who developed a nonhealing wound after lumbar spinal surgery.The wound was successfully treated with vacuum sealing drainage therapy,confirming its feasibility in complex wound healing.CASE SUMMARY The patient was a 76-year-old female with lung cancer,positron emission tomography/computed tomography showed bone metastasis in L2 and L3 vertebrae.After 2 months of local radiotherapy to the lumbar spine,symptoms did not improve and pain worsened.She had lumbar lesion clearance and internal fixation surgery,but developed a nonhealing wound of approximately 15 cm postoperatively.After 12 rounds of clearing necrotic and unhealthy tissue,78 days of negative pressure therapy promoted granulation tissue growth and wound healing,resulting in wound healing.CONCLUSION Vacuum sealing drainage therapy has shown efficacy in treating nonhealing wounds after radiotherapy,promoting wound healing and reducing infection risk.展开更多
Background:Lung metastases often occur after orthotopic liver transplantation(OLT)for hepatocellular carcinoma(HCC).This study aimed to evaluate the safety and efficacy of combining hypofractionated radiotherapy(HFRT)...Background:Lung metastases often occur after orthotopic liver transplantation(OLT)for hepatocellular carcinoma(HCC).This study aimed to evaluate the safety and efficacy of combining hypofractionated radiotherapy(HFRT)with tyrosine kinase inhibitors(TKIs)in patients with lung metastases from HCC following OLT.Methods:We retrospectively analyzed forty-eight patients with lung metastases post-OLT for HCC,who underwent concurrent HFRT and TKIs between July 2011 and August 2022.The primary endpoint was progression-free survival(PFS),and secondary endpoints included overall survival(OS),local control rate(LCR),in-field objective response rate(ORR),and treatment-related side effects.Results:The median follow-up duration was 42.3 months,with median PFS and OS of 9.9 and 32.7 months,respectively.PFS rates at 1,2,and 3 years were 33.3%,20.8%,and 12.5%,respectively,whereas corresponding OS rates were 91.7%,70.8%,and 33.3%,respectively.Independent adverse factors for PFS included the presence of>3 lung metastases,interval time from OLT to lung metastasis<1 year,and post-HFRT lymphocyte nadir<0.8×10^(9)/L.For OS,independent adverse factors included shorter PFS time,shorter intervals from OLT to lung metastasis,and post-HFRT lymphocyte nadirs<0.8×10^(9)/L.The 1-and 2-year LCRs for lung metastases were 100%and 85.3%,respectively.The best in-field ORR was 95.5%,with no adverse events exceeding grade 2.Radiation pneumonitis occurred in 32 patients(66.7%),with grade 1 in 28 patients(58.3%)and grade 2 in 4 patients(8.3%).Conclusions:The combination of HFRT with TKIs is a feasible,safe,and promising approach for treating lung metastases from HCC post-OLT.展开更多
BACKGROUND The optimal sequencing of immune checkpoint inhibitor(ICI)and brain radiotherapy in the management of brain metastasis from non-small cell lung cancer(NSCLC)is unclear.AIM To evaluate the survival of concur...BACKGROUND The optimal sequencing of immune checkpoint inhibitor(ICI)and brain radiotherapy in the management of brain metastasis from non-small cell lung cancer(NSCLC)is unclear.AIM To evaluate the survival of concurrent ICI and consolidation ICI in NSCLC patients treated with brain radiotherapy.METHODS We retrospectively analyzed NSCLC patients treated with brain radiotherapy and ICI.Treatment response and survival were estimated.The cox proportional hazards regression model was utilized to investigate the association between overall survival and clinical variables.RESULTS There were 54 patients in concurrent ICI and radiotherapy group,and 62 individuals treated with radiotherapy followed by consolidation ICI.The objective response rates were similar between the two group.The median progression free survival was significantly high in the concurrent ICI group compared with consolidation ICI group(9.56 months vs 8.15 months,P=0.038).In addition,the median overall survival was 22.08 months in the concurrent ICI group,clearly longer than that in the consolidation group(13.24 months,P=0.009).CONCLUSION In NSCLC patients with brain metastases,our analyses suggested that radio therapy concurrent with ICI was associated with significant benefit compared with radiotherapy followed by consolidation ICI.展开更多
文摘Purpose: To investigate the dosimetric characteristics of a low energy photon intra-operative radiotherapy (IORT) system and explore its potential limitation in clinical application. Methods: A special water phantom, a parallel-plate ionization chamber and an electrometer were used to measure the depth dose rate, isotropy of dose distribution in X/Y plane, dosimetry reproducibility of bare probe and spherical applicators of different size which were used in comparison with the system data. Results: The difference in depth dose rate between the measurement and system data for bare probe is -2.16% ± 1.36%, the range of the relative deviation for isotropy in the X/Y plane is between -1.9% and 2.1%. The difference in depth dose rate, transfer coefficient, isotropy in X/Y plane between the measurement and system data for the whole set of spherical applicators is -10.0% - 2.3%, -8.9% - 4.2% and -1.6% - 2.6%, respectively. Higher surface dose rate and steeper gradient depth dose are observed in smaller spherical applicators. The depth dose rate and isotropy for bare probe and spherical applicators have been shown good reproducibility. The uncertainty of measurement is associated with the positioning accuracy, energy response, noise current and correction function f’(R). Conclusions: Thorough commissioning of the low energy photon IORT system helps us better understand the dosimetry characteristics, verify the system data, obtain adequate data for clinical application and routine quality assurance. The steep gradient depth dose and limited treatment range may restrain its potential in clinical application.
文摘Recent advancements in radiotherapy for esophageal cancer have significantly improved treatment outcomes and patient quality of life.Traditional radiotherapy techniques have been enhanced by the integration of advanced imaging and precision targeting technologies,such as intensity-modulated radiotherapy and proton therapy,which allow for more accurate tumor targeting while minimizing damage to surrounding healthy tissues.Additionally,combining radiotherapy with immunotherapy has shown promising results,leveraging the body’s im-mune response to enhance the effectiveness of cancer treatment.Studies have also highlighted the benefits of neoadjuvant chemoradiation followed by surgical resection,which has been associated with improved overall survival rates com-pared to radiotherapy alone.These innovations are paving the way for more effe-ctive and personalized treatment strategies,offering new hope for patients with esophageal cancer.
基金supported by the Young Talents Program of Jiangsu Cancer Hospital(Grant No.QL201802)the Science and Technology Development Fund of Jiangsu Cancer Hospital(Grant No.ZL202105).
文摘The present study assessed the efficacy and safety of thoracic radiotherapy(TRT)following first-line chemotherapy or chemoimmunotherapy in patients with extensive-stage small cell lung cancer(ES-SCLC),focusing on the influence of different TRT timing strategies(consolidative vs.salvage)on survival rates.We retrospectively analyzed a total of 54 patients with ES-SCLC treated between January 2019 and July 2022.Patients receiving consolidative TRT(cTRT)within three months after completion of first-line treatment were compared with those receiving salvage TRT(sTRT)after disease progression.The primary endpoints were overall survival(OS),progression-free survival(PFS),locoregional-free survival(LRFS),and distant metastasis-free survival(DMFS);the secondary endpoint included safety.The cTRT group(n=41)showed significantly longer median OS(26.6 vs.14.8 months,P=0.048),PFS(12.9 vs.3.5 months,P<0.0001),and DMFS(10.7 vs.3.4 months,P=0.0044)than the sTRT group(n=13).Multivariate analysis revealed that cTRT was an independent,favorable prognostic factor.No significant differences in OS or LRFS were observed between high-dose(≥50 Gy)and low-dose(<50 Gy)TRT.Hematologic and respiratory toxicities were the most frequently reported adverse events,with acceptable tolerability.In conclusion,cTRT after chemoimmunotherapy significantly improves survival outcomes for ES-SCLC patients,and low-dose TRT may be a suitable option.
文摘This editorial explores the potential integration of non-Western medicine into radiotherapy for cervical cancer.While radiotherapy remains a radical treatment for cervical cancer,its associated toxicity and decline in quality of life can significantly impact patients’lives.Currently,most treatments are supportive,with no specific treatment options available in Western medicine.Non-Western medicine,often less toxic and easier to administer,has shown promising results when used alongside radiotherapy for cervical cancer.Despite these potential benefits,challenges such as limited evidence and restricted application areas persist.While non-Western medicines may offer potential improvements in chemoradiotherapy outcomes for cervical cancer,further research is necessary to substantiate these benefits.
基金Supported by The Suzhou Medical Center,No.Szlcyxzx202103The National Natural Science Foundation of China,No.82171828+15 种基金The Key R and D Plan of Jiangsu Province(Development of Social),No.BE2021652The Subject Construction Support Project of The Second Affiliated Hospital of Soochow University,No.XKTJHRC20210011The Wu Jieping Medical Foundation,No.320.6750.2021-01-12The Special Project of"Technological Innovation"Project of CNNC Medical Industry Co.Ltd,No.ZHYLTD2021001The Suzhou Science and Education Health Project,No.KJXW2021018Foundation of Chinese Society of Clinical Oncology,No.Y-pierrefabre202102-0113 and No.Y-XD202002/zb-0015The Beijing Bethune Charitable Foundation,No.STLKY0016The Research Projects of China Baoyuan Investment Co.Ltd,No.270004The Suzhou Gusu Health Talent Program,No.GSWS2022028The Open Project of State Key Laboratory of Radiation Medicine and Protection of Soochow University,No.GZN1202302The New Medical Technology Project of the Second Affiliated Hospital of Soochow University,No.23zl001The Multi-center Clinical Research Project for Major Diseases in Suzhou,No.DZXYJ202304The Postgraduate Research and Practice Innovation Program of Jiangsu Province,No.SJCX24_1814The Gusu Health Talent Research Fund,No.GSWS2022053The National Natural Science Foundation of China,No.82102824The Scientific Research Program for Young Talents of China National Nuclear Corporation。
文摘BACKGROUND Bone is a major site of metastasis in nasopharyngeal carcinoma(NPC).Recently,nuclear factor kappa-beta ligand(RANKL)inhibitors have garnered attention for their ability to inhibit osteoclast formation and bone resorption,as well as their potential to modulate immune functions and thereby enhance the efficacy of programmed cell death protein 1(PD-1)inhibitor therapy.CASE SUMMARY We present a case of a patient with NPC who developed sternal stalk metastasis and multiple bone metastases with soft tissue invasion following radical chemoradiotherapy and targeted therapy.Prior to chemotherapy,the patient experienced severe bone marrow suppression and opted out of further chemotherapy sessions.However,the patient received combination therapy,including RANKL inhibitors(denosumab)alongside PD-1,radiotherapy,and granulocyte-macrophage colonystimulating factor(PRaG)therapy(NCT05435768),and achieved 16 months of progression-free survival and more than 35 months of overall survival,without encountering any grade 2 or higher treatment-related adverse events.CONCLUSION Denosumab combined with PRaG therapy could be a new therapeutic approach for the second-line treatment in patients with bone metastases.
文摘Background: Early research describing the concept of intensity-modulated conformal radiotherapy (IMRT) was based on 7 to 9 beams to reach an adequate level of modulation. Nevertheless, its implementation demands significant resources. Our objective was to compare the compliance and homogeneity of target dose distribution between simplified IMRT and 3D-CRT in patients with cervical cancer and to assess the clinical value of simplified IMRT. Materials and Methods: From 2016 to 2017, 17 patients with stage IIB - IIIC cervical cancer were treated with external beam radiotherapy using simplified IMRT (12 cases) or 3DCRT (05 cases) and brachytherapy. Prior to radiotherapy, CT scans were conducted to delineate the target volume. The clinical target volume (CTV) included the uterus, primary tumor, supravaginal portion of the cervix, paracervical tissue, common iliac, internal and external iliac lymph nodes, obturator, and pre sacral lymph nodes, and the surrounding tissues. If the lower vagina was involved, the target volume included the whole vagina. The planning target volume (PTV) included the CTV with 1 cm anteriorly and 0.5 cm in all other directions. The PTV received 95% of 45 Gy (1.8 Gy/25 fraction). Dose-volume histogram, conformity index, homogeneity index, and treatment time per fraction were compared. Results: The 3D-CRT plan was more homogeneous than the simplified IMRT plan, while the simplified IMRT plan was more conformal. The volume of small bowels that received high-dose radiation significantly increased with simplified IMRT compared to 3D-CRT. Treatment time per fraction was 6 and 13 minutes for 3D-CRT and simplified IMRT, respectively. Conclusion: The simplified IMRT treatment plan is technically and dosimetrically acceptable and an alternative to the classic 3D-CRT plan for cervical cancer. It provides better dose distribution than 3D-CRT. However, the 3D-CRT treatment plan significantly reduced the overall treatment time per fraction.
文摘A recent study by Zhang et al developed a neural network-based predictive model for estimating doses to the uninvolved liver during stereotactic body radiation therapy(SBRT)in liver cancer.The study reported a significant advancement in personalized radiotherapy by improving accuracy and reducing treatment-related toxicity.The model demonstrated strong predictive performance with R-values above 0.8,indicating its potential to improve treatment consistency.However,concerns arise from the small sample size and exclusion criteria,which may limit generalizability.Future studies should incorporate larger,more diverse patient cohorts,explore potential confounding factors such as tumor characteristics and delivery technique variability,and address the long-term effects of SBRT.
文摘BACKGROUND Older patients are more likely to have a poor performance status and comor-bidities.There is a reluctance to extensively investigate and treat older patients.As elderly individuals and patients with neoplasms each increase in number,palliative treatment of older patients is expected to grow as an issue.AIM To investigated the role of palliative radiotherapy in older patients and patients who were expected to demonstrate a therapeutic effect.METHODS From February 2019 to February 2022,33 patients aged≥80 years underwent palliative radiotherapy.The prognosis in palliative care study predictor(PiPS),palliative prognostic index(PPI),and delirium-palliative prognostic score(D-PaP)models were used for prognosis prediction.D-PaP scores calculated according to the doctor's prediction of clinical prediction of survival(CPS)were excluded and then analyzed for comparison.Radiation was prescribed at a dose of 2.5-7 Gy per fraction,up to a median of 39 Gy10(range,28-75 Gy10).RESULTS The median follow-up was 2.4 months(range,0.2-27.5 months),and 28 patients(84.8%)showed subjective symptom improvements following treatment.The 2-and 6-month survival rates of all patients were 91.5%and 91.5%,respectively.According to regression analysis,the performance status index,symptom type,and radiation dose all showed no significant correlation with the treatment re-sponse.When survival was expected for>55 days in the PiPS model,the 2-month survival rate was 94.4%.For patients with PPI and D-PaP-CPS values of 0-3.9 points,the 2-month survival rates were 90.0%and 100%,respectively.For patients with a score of≥4 points,the 2-month survival rates were 37.5%and 0%,res-pectively.Core Tip:This is a retrospective study to investigate the role of palliative radiotherapy in older patients and patients who were expected to demonstrate a great therapeutic effect.The prognosis in palliative care study predictor,palliative prognostic index,and delirium-palliative prognostic score models were used for prognosis prediction.Most of patients showed subjective symptom improvements following treatment.The prognosis prediction model showed good correlation with survival.In order to increase the therapeutic effectiveness in palliative radiotherapy,it is necessary to assess a patient's exact prognosis and select appropriate patients accordingly.INTRODUCTION The incidence of cancer is high among individuals 60-69 years old and is 11 times greater among those≥65-years-old compared to those<65-years-old.For this reason,about half of all cancer cases are diagnosed in individuals aged≥70 years,and older patients account for a large portion of the total population regarding the prevalence of cancer[1].Cancer is one of the most significant diseases in older patients.About 60%of all cancer-related deaths occur in older patients aged 70 years[1,2].Moreover,cancer accounts for about one-third of the causes of death in the elderly population[1,2].When choosing a cancer treatment,both the characteristics of the cancer and the overall health status of the patient,such as their general condition and any underlying diseases,should be considered[2].Older patients have a shorter life expectancy than younger patients;moreover,they typically have many accompanying underlying diseases and have a poorer general condition.For this reason,older patients are often rejected from receiving active testing and treatment services.Therefore,even if other factors,such as the underlying disease,are the same in young and old patients,older patients typically receive less treatment due to the simple fact that they are older[3].Palliative treatment is a treatment approach that improves the pain and symptoms of a patient and their quality of life.Although palliative treatment is applicable regardless of patient age and the type and severity of their disease,most patients requiring palliative treatment are cancer patients.Palliative radiotherapy is relatively effective for cancer patients and tends to be a well-tolerated treatment.Although some studies have reported the usefulness of palliative radiotherapy in elderly patients,a large number of patients and caregivers are not receiving treatment due to fears of treatment,the risks of side effects,and doubts about treatment effectiveness[1].Since actual age is not always associated with physical ability,the determination of treatment based solely on age can be an obstacle preventing appropriate treatment opportunities.The importance of palliative care is increasing due to the recent growth of the elderly population,as well as,the increase in cancer incidence,and the changes in traditional views or perceptions,such as a growing acceptance of the pursuit of a dignified death[4].Therefore,in this study,we investigated the role of palliative radiotherapy in older patients and in patients who are expected to show a great therapeutic effect.
基金supported by the Shenzhen Science and Technology Program(grant number:KQTD20180411185028798).
文摘Background:The role of systemic tumor immune environment(STIE)is unclear in hepatocellular carcinoma(HCC).This study aimed to exam the cells in the STIE,their changes after transarterial chemoembolisation(TACE),stereotactic body radiotherapy(SBRT),and immunotherapy(IO)and explore their significance in the treatment response of patients with unresectable HCC.Methods:This is a prospective biomarker study of patients with unresectable HCC.The treatment was sequential TACE,SBRT(27.5-40 Gy/5 fractions),and IO.The treatment response was assessed according to modified Re-sponse Evaluation Criteria in Solid Tumors(mRECIST)by magnetic resonance imaging(MRI)after 6 months of treatment.Longitudinal data of STIE cells was extracted from laboratory results of complete blood cell counts,in-cluding leukocytes,lymphocytes,neutrophils,monocytes,eosinophils,basophils,and platelets.Peripheral blood samples were collected at baseline and after TACE,SBRT,and IO for T-lymphocyte subtyping by flow cytometry.Generalized estimation equation was employed for longitudinal analyses.Results:A total of 35 patients with unresectable HCC were enrolled:23 patients in the exploratory cohort and 12 in the validation cohort.STIE circulating cells,especially lymphocytes,were heterogenous at baseline and changed differentially after TACE,SBRT,and IO in both cohorts.SBRT caused the greatest reduction of 0.7×10^(9)/L(95%CI:0.3×10^(9)/L-1.0×10^(9)/L,P<0.001)in lymphocytes;less reduction was associated with significantly better treatment response.The analysis of T-lymphocyte lineage revealed that the baseline levels of CD4+T cells(P=0.010),type 1 T helper(Th1)cells(P=0.007),and Th1/Th17 ratios(P=0.001)were significantly higher in responders,while regulatory T(Treg)cells(P=0.002),Th17 cells(P=0.047),and Th2/Th1 ratios(P=0.028)were significantly higher in non-responders.After treatment with TACE,SBRT and IO,T-lymphocyte lineage also changed differentially.More reductions were observed in CD25^(+)CD8^(+)T cells and CD127^(+)CD8^(+)T cells after SBRT in non-responders,while increases in natural killer T(NKT)cells after SBRT(10.4%vs.3.4%,P=0.001)and increases in the lymphocyte counts were noted during IO in responders.Conclusions:STIE cells are significant for treatment response,can be reshaped differentially after TACE,SBRT,and IO.The most significant changes of T-lymphocyte lineage are SBRT associated modulations in CD25^(+)CD8^(+)T cells,CD127^(+)CD8^(+)T cells,and NKT cells,which also have significant effects on the ultimate treatment response after TACE-SBRT-IO(ClinicalTrails.gov identifier:GCOG0001/NCT05061342).
基金supported by the Zhejiang Provincial Natural Science Foundation of China(LY24H300001)the Medical and Health Research Project of Zhejiang Province(KY202302130009)National Health Service Research Project(WKZX2024CX501205).
文摘Objectives:Triphenylphosphine(TPP)and Doxorubicin(DOX)were conjugated to obtain Triphenylphosphine-Doxorubicin(TPP-DOX),which was applied in tumor cells for enhancement of DOX in mitochondria targeting.The study focused on investigating the anti-tumor effect of TPP-DOX in combination with radiotherapy throughout in vitro and in vivo studies.Methods:TPP-DOX was synthesized using the carbodiimide method.In vitro experiments were conducted with 4T1 cells(mouse breast cancer cell line)to assess apoptosis induction,mitochondrial targeting,reactive oxygen species(ROS)production,and mitochondrial membrane potential.The research evaluates the effects of TPP-DOX,DOX,and their combinations with radiotherapy.A nude mouse tumor heterograft model was established to investigate the synergistic effect of TPP-DOX and radiotherapy.Results:TPP-DOX was successfully synthesized and scrupulously verified.In vitro experiments showed that compared to DOX,TPP-DOX exhibited enhanced tumor cytotoxicity,improved cellular uptake in 4T1 cells,and increased apoptosis induction.Combined with radiotherapy,TPP-DOX promoted mitochondrial ROS production,reduced mitochondrial membrane potential,and amplified its anti-tumor effect.In vivo experiment confirmed that TPP-DOX combined with radiotherapy exhibited superior anti-tumor activity,promoted tumor tissue apoptosis,inhibited tumor angiogenesis,and showed a favorable in vivo safety profile.Conclusion:The study confirmed that when combined with radiotherapy,TPP-DOX promoted tumor cell apoptosis,and effectively enhanced the anti-tumor effect.In sensitive cells,TPP-DOX demonstrates comparable efficacy to DOX when combined with radiotherapy.TPP-DOX holds significant potential for a broader spectrum of applications and emerges as a valuable candidate for clinical application.These findings provide a promising and efficient therapeutic strategy for tumor treatment with improved efficacy and safety.
基金Supported by National Natural Science Foundation of China,No.81602792The Natural Science Foundation of the Jiangsu Higher Education Institutions of China,No.23KJB310023+5 种基金Jiangsu Provincial Medical Key Discipline,No.ZDXK202235The Maternal and Child Health Research Project of Jiangsu Province,No.F202210The Project of State Key Laboratory of Radiation Medicine and Protection,Soochow University,No.GZK1202101Suzhou Science and Technology Development Plan Project,No.KJXW2020008BOXI Natural Science Cultivation Foundation of China of The First Affiliated Hospital of Soochow University,No.BXQN202107Clinical Diagnosis and Treatment Technology Innovation Project Youth Characteristic Technology Project of The First Affiliated Hospital of Soochow University,No.2100201.
文摘BACKGROUND Currently,there is limited research examining the relationship between anxiety,depression,coping styles,and illness uncertainty in patients with cervical cancer(CC)undergoing radiotherapy.Addressing this gap could provide valuable insights and more reliable evidence for clinical practice targeting this patient population.AIM To analyze the anxiety,depression,and coping styles of patients with CC undergoing radiotherapy and explore their correlations with illness uncertainty.METHODS A total of 200 patients with CC undergoing radiotherapy at The First Affiliated Hospital of Soochow University between June 2018 and June 2022 were enrolled.Anxiety and depression were assessed using the Hospital Anxiety and Depression Scale(HADS),comprising subscales for anxiety(HADS-A)and depression(HADS-D).Coping styles were evaluated using the Jalowiec Coping Scale(JCS-60),comprising dimensions such as confrontive,evasive,optimistic,fatalistic,emotive,palliative,supportive,and self-reliant.Illness uncertainty was measured using the Mishel Uncertainty in Illness Scale(MUIS),encompassing ambiguity,complexity,information deficit,and unpredictability.Correlations among anxiety,depression,coping styles,and illness uncertainty were analyzed.RESULTS During radiotherapy,the mean scores were 7.12±3.39 for HADS-A,6.68±3.49 for HADS-D,1.52±0.23 for JCS-60,and 93.40±7.44 for MUIS.Anxiety(HADS-A≥8)was present in 39.5%of patients,depression(HADS-D≥8)in 41.0%,and both in 14.0%.Anxiety was significantly positively correlated with ambiguity,unpredictability,and total MUIS score(P<0.05).Depression was significantly positively correlated with ambiguity,information deficit,unpredictability,and total MUIS score(P<0.05).Most patients adopted an optimistic coping style,whereas the emotive style was least utilized.Evasive,fatalistic,and emotive coping styles were significantly positively correlated with illness uncertainty,whereas the self-reliant style was significantly negatively correlated with unpredictability(P<0.05).CONCLUSION Anxiety,depression,and coping styles in patients with CC undergoing radiotherapy correlate significantly with their level of illness uncertainty.Medical staff should address patients’psychological status and coping strategies by providing targeted information to reduce negative emotions,foster adaptive coping styles,and decrease illness uncertainty.
基金funded by the National Key Research and Development Program of China(Grant No.2023YFC3402700)Shanghai Municipal Natural Science Foundation(Grant No.22ZR1411200)+2 种基金China Postdoctoral Science FundGeneral Fund(Grant No.2022M720779)Research Fund of Zhongshan Hospital Affiliated to Shanghai Fudan University for Young Scientists(Grant No.2023ZSQN26)National Natural Science Foundation of China(Grant Nos.82403999 and 82073479)。
文摘Objective:Although the role of circular RNAs(circRNAs)in tumor progression and immune regulation is well-known,the specific circ RNA molecules that mediate immune responses after radiotherapy(RT)and the underlying mechanisms have not been identified.Methods:Cytometry with time-of-flight(CyTOF)was used to analyze blood samples from patients with liver cancer exhibiting abscopal effects(AEs)after stereotactic body radiotherapy(SBRT)to quantify the number of dendritic cells(DCs)and CD8+T cells and interferon-beta(IFN-β)level.circTMEM56 and IFN-βlevels were measured in 76 patients with liver cancer using q PCR and ELISA.Immunohistochemistry validated circTMEM56 and CD141 staining in tissues.The interaction between circTMEM56,miR-136-5p,and STING,as well as the impact on anti-tumor immunity,was verified using circTMEM56-specific probes,dual-luciferase activity assays,proteomics analysis,and western blot analysis.Results:The role of circTMEM56 in enhancing anti-tumor immunity and response to RT in hepatocellular carcinoma(HCC)was determined.Higher circTMEM56 levels were linked to an improved RT response and better clinical outcomes in patients with HCC.circTMEM56 enhanced cGAS-STING signaling,increased the number of tumor-infiltrating CD8+T cells,and elevated the serum IFN-βlevels.Moreover,circTMEM56 administration significantly boosted the response to RT in tumors with low circTMEM56 expression.Conclusions:High circTMEM56 expression in HCC modulates the distant effects of HCC RT by activating the cGAS-STING pathway to reshape the tumor microenvironment.This study provides a new approach to improve RT efficacy for HCC.
基金Supported by the National Natural Science Foundation of China,No.81602792 and No.12205215and Science and Technology Program of Nantong,No.JC12022103.
文摘BACKGROUND Radiation resistance limits radiotherapy efficacy in esophageal squamous cell carcinoma(ESCC).The tumor microenvironment,particularly adipocytes,plays a role in promoting cancer progression.Extracellular vesicles and microRNAs(miRNAs)regulate gene expression and hold prognostic potential for esophageal carcinoma.Elucidating radioresistance mechanisms and identifying radiosensitization targets can help enhance radiotherapy efficacy for esophageal cancer.AIM To investigate the potential role of miRNAs derived from adipocyte exosomes as prognostic markers for radiotherapy efficacy in ESCC.METHODS Free adipocytes were isolated from human thoracic adipose tissue.A co-culture model of adipocytes and ESCC cells was established to observe colony formation and cell survival post-irradiation.ESCC cell apoptosis was assessed by flow cytometry.Western Blot and immunofluorescence assays were performed to evaluate DNA damage in ESCC cells post-irradiation.Adipocyte-derived exosomes were isolated by ultracentrifugation and identified by electron microscopy.A similar set of experiments was performed on ESCC cells to analyze cell survival,apoptosis,and DNA damage post-radiation exposure.Exosomes from adipose tissue and serum exosomes from ESCC patients pre-and post-radiotherapy were subjected to high-throughput miRNA-sequencing and validated using real-time quantitative polymerase chain reaction.The correlation between potential target miRNAs and the short-term prognosis of radiotherapy in ESCC was evaluated by receiver operating characteristic curve analysis.RESULTS Co-culturing adipocytes with ESCC cells enhanced radioresistance,as evidenced by increased colony formation.Adipocyte co-culture reduced ESCC cell apoptosis and DNA damage post-radiation.Adipocyte-derived exosomes similarly conferred radioresistance in ESCC cells,decreasing apoptosis and DNA damage post-irradiation.Highthroughput miRNA-sequencing identified miR-660-5p in serum and adipose tissue exosomes.Patients with high expression of serum exosome miR-660-5p showed poor prognosis after radiotherapy.CONCLUSION Adipocyte-derived exosomal miR-660-5p is a potential biomarker for evaluating radiotherapy efficacy in ESCC.
基金support from the National Natural Science Foundation of China(Grant Nos.:82272751 and 82202958)the Natural Science Foundation of Shandong,China(Grant No.:ZR2021LSW002)+6 种基金the Science and Technology Program of Jinan,China(Grant Nos.:202225019 and 202225013)to Man Huthe Shandong Postdoctoral Innovation Program,China(Grant No.:SDCX-ZG-202302011)Beijing Science and Technology Innovation Medical Development Foundation,China(Grant No.:KC2023-JX-0288-BQ26)to Yong Wangthe Natural Science Foundation of China(Grant No.:NSFC82303676)the Natural Science Foundation of Shandong(Grant No.:ZR2023QH208)the China Postdoctoral Science Foundation(Grant No.:2023M732125)the Taishan Scholar Project Special Fund(Grant No.:tsqn202312368)to Kewen He.
文摘Real-time,noninvasive programmed death-ligand 1(PD-L1)testing using molecular imaging has enhanced our understanding of the immune environments of neoplasms and has served as a guide for immunotherapy.However,the utilization of radiotracers in the imaging of human brain tumors using positron emission tomography/computed tomography(PET/CT)remains limited.This investigation involved the synthesis of[18F]AlF-NOTA-PCP2,which is a novel peptide-based radiolabeled tracer that targets PD-L1,and evaluated its imaging capabilities in orthotopic glioblastoma(GBM)models.Using this tracer,we could noninvasively monitor radiation-induced PD-L1 changes in GBM.[18F]AlF-NOTA-PCP2 exhibited high radiochemical purity(>95%)and stability up to 4 h after synthesis.It demonstrated specific,high-affinity binding to PD-L1 in vitro and in vivo,with a dissociation constant of 0.24 nM.PET/CT imaging,integrated with contrast-enhanced magnetic resonance imaging,revealed significant accumulation of[18F]AlF-NOTA-PCP2 in orthotopic tumors,correlating with blood-brain barrier disruption.After radiotherapy(15 Gy),[18F]AlF-NOTA-PCP2 uptake in tumors increased from 9.51%±0.73%to 12.04%±1.43%,indicating enhanced PD-L1 expression consistent with immunohistochemistry findings.Fractionated radiation(5 Gy×3)further amplified PD-L1 upregulation(13.9%±1.54%ID/cc)compared with a single dose(11.48%±1.05%ID/cc).Taken together,[18F]AlF-NOTA-PCP2 may be a valuable tool for noninvasively monitoring PD-L1 expression in brain tumors after radiotherapy.
基金Supported by the National Natural Science Foundation of China,No.82270634Third Affiliated Hospital of Naval Medical University,No.tf2024yzyy01.
文摘Hepatocellular carcinoma(HCC)is one of the most common malignant tumors globally and is the most prevalent type of primary liver cancer,posing a heavy burden on global health.Surgical resection and liver transplantation are the gold standard for the radical treatment of HCC.However,due to the heterogeneity and high invasiveness of HCC,the rates of local and distant recurrence are extremely high,with over 70%of patients experiencing recurrence within 5 years after treatment,significantly impacting the long-term quality of life.Therefore,researchers are exploring other treatment methods to reduce tumor recurrence and improve patient survival.To date,extensive research has concentrated on new alternative therapies,including radiotherapy(e.g.,selective internal radiotherapy),targeted drug therapy(e.g.,sorafenib and lenvatinib),and immunotherapy(e.g.,immune checkpoint inhibitors),which have played an integral role in the comprehensive treatment of HCC.This review mainly focuses on the cutting-edge advancements in these treatment methods for HCC and their potential role in reducing HCC recurrence.
文摘BACKGROUND Definitive chemoradiotherapy is the standard treatment for unresectable,locally advanced esophageal cancer.However,radiotherapy(RT)often affects the immune system of patients.One of the possible mechanisms of lymphopenia after RT is that a large number of circulating lymphocytes in the systemic and pulmonary circulation will be killed by more sessions of low-dose radiation.The impact of dose-volume parameters of organs at risk(OARs)on absolute lymphocyte count(ALC)and the relationship between the extent of lymphocyte count reduction and survival prognosis in patients with middle and lower thoracic esophageal squamous cell carcinoma(ESCC)both remain difficult to determine.AIM To determine the relationship between RT parameters,lymphocyte count and survival prognosis of esophageal cancer patients.METHODS The clinical data of 112 patients with stage I-III ESCC who received definitive RT were analyzed retrospectively.The ALC values before RT,weekly during RT,and within 1 month after RT were determined.Logistic regression was used to evaluate the correlation between the parameters of radiation OARs and the lowest point of the ALC.Kaplan-Meier and Cox regression analyses were used to evaluate the relationship between the lowest point of the ALC and patient survival during RT.RESULTS The median value of the ALC before treatment was 1.57×10^(9)cells/L,and 32 patients(28.6%)showed grade 4 ALC reduction during RT.The reduction in G4 ALC during RT was significantly associated with poor overall survival(OS)and progression-free survival.Multivariate analysis showed that stage III tumors(P=0.003),high heart V_(10)(P=0.046),high lung V_(5)(P=0.048),and high lung V_(20)(P=0.031)were associated with G4 ALC reduction during RT.CONCLUSION The reduction in G4 ALC is related to OS.Joint evaluation of the tumor stage and dose volume parameters has predictive value for G4 ALC reduction and OS.
文摘Objective:Radiotherapy(RT)is the definitive treatment for stageⅡnasopharyngeal carcinoma(NPC),which is classified as stagesⅠA andⅠB in the latest ninth edition of American Joint Committee on Cancer(AJCC)/Union for International Cancer Control(UICC).A crucial question is whether concurrent chemo-radiotherapy(CCRT)could derive additional benefits to this recent“down-staging”subgroup of NPC patients.This study aimed to interrogate clinical and radiomic features for predicting 5-year progression-free survival(PFS)of stageⅡNPC treated with RT alone or CCRT.Methods:Imaging and clinical data of 166 stageⅡNPC(eighth edition AJCC/UICC)patients were collected.Data were allocated into training,internal testing,and external testing sets.For each case,851 radiomic features were extracted and 10 clinical features were collected.Radiomic and clinical features most associated with the 5-year PFS were selected separately.A combined model was developed using multivariate logistic regression by integrating selected features and treatment option to predict 5-year PFS.Model performances were evaluated by area under the receiver operating curve(AUC),prediction accuracy,and decision curve analysis.Survival analyses including Kaplan-Meier analysis and Cox regression model were performed for further analysis.Results:Thirteen radiomic features,three clinical features,and treatment option were considered for model development.The combined model showed higher prognostic performance than using either.For the merged testing set(internal and external testing sets),AUC is 0.76(combined)vs.0.56-0.80(clinical or radiomic alone)and accuracy is 0.75(combined)vs.0.62-0.73(clinical or radiomic alone).Kaplan-Meier analysis using the combined model showed significant discrimination in PFS of the predicted low-risk and high-risk groups in the training and internal testing cohorts(P<0.05).Conclusions:Integrating with clinical and radiomic features could provide prognostic information on 5-year PFS under either treatment regimen,guiding individualized decisions of chemotherapy based on the predicted treatment outcome.
文摘BACKGROUND The current method of cleaning and changing dressings for non-healing lumbar incisions post-radiotherapy is time-consuming and laborious,with very poor results.We here report a patient with radiation dermatitis who developed a nonhealing wound after lumbar spinal surgery.The wound was successfully treated with vacuum sealing drainage therapy,confirming its feasibility in complex wound healing.CASE SUMMARY The patient was a 76-year-old female with lung cancer,positron emission tomography/computed tomography showed bone metastasis in L2 and L3 vertebrae.After 2 months of local radiotherapy to the lumbar spine,symptoms did not improve and pain worsened.She had lumbar lesion clearance and internal fixation surgery,but developed a nonhealing wound of approximately 15 cm postoperatively.After 12 rounds of clearing necrotic and unhealthy tissue,78 days of negative pressure therapy promoted granulation tissue growth and wound healing,resulting in wound healing.CONCLUSION Vacuum sealing drainage therapy has shown efficacy in treating nonhealing wounds after radiotherapy,promoting wound healing and reducing infection risk.
基金supported by grants from the National Natu-ral Science Foundation of China(82102913 and 82102823)the Special Clinical Research Program of the Health Industry,Shanghai Municipal Health Commission(202340179).
文摘Background:Lung metastases often occur after orthotopic liver transplantation(OLT)for hepatocellular carcinoma(HCC).This study aimed to evaluate the safety and efficacy of combining hypofractionated radiotherapy(HFRT)with tyrosine kinase inhibitors(TKIs)in patients with lung metastases from HCC following OLT.Methods:We retrospectively analyzed forty-eight patients with lung metastases post-OLT for HCC,who underwent concurrent HFRT and TKIs between July 2011 and August 2022.The primary endpoint was progression-free survival(PFS),and secondary endpoints included overall survival(OS),local control rate(LCR),in-field objective response rate(ORR),and treatment-related side effects.Results:The median follow-up duration was 42.3 months,with median PFS and OS of 9.9 and 32.7 months,respectively.PFS rates at 1,2,and 3 years were 33.3%,20.8%,and 12.5%,respectively,whereas corresponding OS rates were 91.7%,70.8%,and 33.3%,respectively.Independent adverse factors for PFS included the presence of>3 lung metastases,interval time from OLT to lung metastasis<1 year,and post-HFRT lymphocyte nadir<0.8×10^(9)/L.For OS,independent adverse factors included shorter PFS time,shorter intervals from OLT to lung metastasis,and post-HFRT lymphocyte nadirs<0.8×10^(9)/L.The 1-and 2-year LCRs for lung metastases were 100%and 85.3%,respectively.The best in-field ORR was 95.5%,with no adverse events exceeding grade 2.Radiation pneumonitis occurred in 32 patients(66.7%),with grade 1 in 28 patients(58.3%)and grade 2 in 4 patients(8.3%).Conclusions:The combination of HFRT with TKIs is a feasible,safe,and promising approach for treating lung metastases from HCC post-OLT.
文摘BACKGROUND The optimal sequencing of immune checkpoint inhibitor(ICI)and brain radiotherapy in the management of brain metastasis from non-small cell lung cancer(NSCLC)is unclear.AIM To evaluate the survival of concurrent ICI and consolidation ICI in NSCLC patients treated with brain radiotherapy.METHODS We retrospectively analyzed NSCLC patients treated with brain radiotherapy and ICI.Treatment response and survival were estimated.The cox proportional hazards regression model was utilized to investigate the association between overall survival and clinical variables.RESULTS There were 54 patients in concurrent ICI and radiotherapy group,and 62 individuals treated with radiotherapy followed by consolidation ICI.The objective response rates were similar between the two group.The median progression free survival was significantly high in the concurrent ICI group compared with consolidation ICI group(9.56 months vs 8.15 months,P=0.038).In addition,the median overall survival was 22.08 months in the concurrent ICI group,clearly longer than that in the consolidation group(13.24 months,P=0.009).CONCLUSION In NSCLC patients with brain metastases,our analyses suggested that radio therapy concurrent with ICI was associated with significant benefit compared with radiotherapy followed by consolidation ICI.
