Potential of non-Western medicines in chemoradiotherapy for cervical cancer

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.

Impacts of Nutlin-3a and exercise on murine double minute 2-enriched glioma treatment

Recent research has demonstrated the impact of physical activity on the prognosis of glioma patients,with evidence suggesting exercise may reduce mortality risks and aid neural regeneration.The role of the small ubiquitin-like modifier(SUMO)protein,especially post-exercise,in cancer progression,is gaining attention,as are the potential anti-cancer effects of SUMOylation.We used machine learning to create the exercise and SUMO-related gene signature(ESLRS).This signature shows how physical activity might help improve the outlook for low-grade glioma and other cancers.We demonstrated the prognostic and immunotherapeutic significance of ESLRS markers,specifically highlighting how murine double minute 2(MDM2),a component of the ESLRS,can be targeted by nutlin-3.This underscores the intricate relationship between natural compounds such as nutlin-3 and immune regulation.Using comprehensive CRISPR screening,we validated the effects of specific ESLRS genes on low-grade glioma progression.We also revealed insights into the effectiveness of Nutlin-3a as a potent MDM2 inhibitor through molecular docking and dynamic simulation.Nutlin-3a inhibited glioma cell proliferation and activated the p53 pathway.Its efficacy decreased with MDM2 overexpression,and this was reversed by Nutlin-3a or exercise.Experiments using a low-grade glioma mouse model highlighted the effect of physical activity on oxidative stress and molecular pathway regulation.Notably,both physical exercise and Nutlin-3a administration improved physical function in mice bearing tumors derived from MDM2-overexpressing cells.These results suggest the potential for Nutlin-3a,an MDM2 inhibitor,with physical exercise as a therapeutic approach for glioma management.Our research also supports the use of natural products for therapy and sheds light on the interaction of exercise,natural products,and immune regulation in cancer treatment.

Radiotherapy dosage:A neural network approach for uninvolved liver dose in stereotactic body radiation therapy for liver cancer

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.

Validation of the prognostic model for palliative radiotherapy in older patients with cancer

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.

Advances in radiotherapy in the treatment of esophageal cancer

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.

Identifying adipocyte-derived exosomal miRNAs as potential novel prognostic markers for radiotherapy of esophageal squamous cell carcinoma

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.

Safety and effectiveness of induction chemoimmunotherapy followed by definitive radiotherapy or concurrent chemoradiotherapy in esophageal squamous cell carcinoma

BACKGROUND Esophageal squamous cell carcinoma(ESCC)is a common malignancy in China,often diagnosed at an advanced stage,with poor prognosis.Standard treatments such as definitive chemoradiotherapy offer limited survival benefits.Recent advances in immune checkpoint inhibitors combined with chemotherapy have shown promise,but their effectiveness and safety in conjunction with radio-therapy for unresectable ESCC require further exploration.AIM To assess the safety and effectiveness of induction chemoimmunotherapy fo-llowed by definitive radiotherapy or concurrent chemoradiotherapy(CCRT)in locally advanced unresectable ESCC.METHODS This retrospective study included 80 patients with locally advanced unresectable ESCC who underwent induction chemoimmunotherapy followed by definitive radiotherapy,recruited from Zhejiang Cancer Hospital.All patients received 2-4 cycles of chemotherapy plus programmed cell death 1/programmed cell death ligand 1 inhibitor,were re-evaluated to be inoperable,then received definitive radiotherapy or CCRT.Primary endpoint was treatment safety and tolerance.SPSS 26.0 software was used for data analysis.Th Kaplan-Meier method was used for survival analysis.RESULTS Thirty-seven(46.3%)patients received CCRT and 43(53.7%)received radiotherapy alone.The most common treatment-related adverse events included radiation esophagitis(32/80,40.0%)and anemia(49/80,61.3%),with 22(27.5%)experiencing grade≥3 adverse events.No treatment-related deaths occurred.After median follow-up of 16.5 months,the median progression-free survival(PFS)was 14.2 months,and median overall survival(OS)was 19.9 months.The 1-year and 2-year PFS and OS were 55.8%and 31.6%,and 67.5%and 44.1%,respectively.Patients with partial response had better outcomes than those with stable disease:1-year PFS 69.4%vs 43.9%(P=0.011)and OS 83.2%vs 48.8%(P=0.007).Induction therapy effectiveness and immunotherapy maintenance were independent prognostic factors for OS.CONCLUSION Chemotherapy combined with programmed cell death 1/programmed cell death ligand 1 inhibitor followed by definitive radiotherapy or CCRT in patients with locally advanced ESCC was safe and effective.

Therapeutic Effects of Stereotactic Radiotherapy on 389 Cases of Brain Glioma

Objective： To investigate the treatment effectiveness and side effects of stereotactic radiotherapy for brain glioma. Methods： From Jun. 1995 to Dec. 1998, 389 cases of brain gliomas were treated by stereotactic radiotherapy, among which 151 cases were treated by stereotactic radiosurgery （SRS） and the other 238 cases, by fractionated stereotactic radiotherapy （FSRT）. In the SRS group, the marginal tumor dose was 20 to 30 Gy （median, 2.6 Gy）. One to 6 isocenters （median, 2.48） and 5 to 21 irradiation arcs （median, 8.45） were applied. In the FSRT group, the per-fraction marginal tumor dose was 8 to 12 Gy with 1 to 6 isocenters （median, 2.53）, 6 to 20 irradiation arcs （median, 8.25） and 2-5 fractions delivered everyday or every other day. Results： Three months after treatment, the complete and partial response rates were 13.9% and 45.7% in SRS group respectively. The stable disease rate was 17.2%. The total effective rate was 76.8%. In FSRT group, the complete and partial remission rates were 19.7% and 47.9% respectively. The stable disease rate was 20.6%. The total effective rate was 88.2%. The total effective rate of FSRT group was higher than that in SRS group （X^2=9.874, P=0.020）. The 1-year, 3-year and 5-year survival rate of all patients was 54.3%, 29.3%, 16.5% respectively. The 1-year, 3-year and 5-year survival rate in SRS group and FSRT group was 52.3% vs 26.5%, 11.9% vs 55.5%, and 31.1 vs 19.3% respectively. There was no significant difference between the two groups （X^2=2.16, P=0.1417）. The brain edema caused by the main radiation was more severe in the SRS group than in FSRT group （X^2=4.916, P=0.027）. Conclusion： It is effective for brain glioma to be treated by stereotactic radiotherapy. Compared with SRS, the FSRT has the advantage of good effect and less side response.

Radiotherapy of high-grade gliomas: current standards and new concepts, innovations in imaging and radiotherapy, and new therapeutic approaches

The current standards in radiotherapy of high-grade gliomas(HGG) are based on anatomic imaging techniques, usually computed tomography(CT) scanning and magnetic resonance imaging(MRI). The guidelines vary depending on whether the HGG is a histological grade 3 anaplastic glioma(AG) or a grade 4 glioblastoma multiforme(GBM). For AG, T2-weighted MRI sequences plus the region of contrast enhancement in T1 are considered for the delineation of the gross tumor volume(GTV), and an isotropic expansion of 15 to 20 mm is recommended for the clinical target volume(CTV). For GBM, the Radiation Therapy Oncology Group favors a two-step technique, with an initial phase(CTV1) including any T2 hyperintensity area(edema) plus a 20 mm margin treated with up to 46 Gy in 23 fractions, followed by a reduction in CTV2 to the contrast enhancement region in T1 with an additional 25 mm margin. The European Organisation of Research and Treatment of Cancer recommends a single-phase technique with a unique GTV, which comprises the T1 contrast enhancement region plus a margin of 20 to 30 mm. A total dose of 60 Gy in 30 fractions is usually delivered for GBM, and a dose of 59.4 Gy in 33 fractions is typically given for AG. As more than 85% of HGGs recur in field, dose-escalation studies have shown that 70 to 75 Gy can be delivered in 6 weeks with relevant toxicities developing in < 10% of the patients. However, the only randomized dose-escalation trial, in which the boost dose was guided by conventional MRI, did not show any survival advantage of this treatment over the reference arm. HGGs are amongst the most infiltrative and heterogeneous tumors, and it was hypothesized that the most highly aggressive areas were missed; thus, better visualization of these high-risk regions for radiation boost could decrease the recurrence rate. Innovations in imaging and linear accelerators(LINAC) could help deliver the right doses of radiation to the right subvolumes according to the dose-painting concept. Advanced imaging techniques provide functional information on cellular density(diffusion MRI), angiogenesis(perfusion MRI), metabolic activity and cellular proliferation [positron emission tomography(PET) and magnetic resonance spectroscopy(MRS)]. All of these non-invasive techniques demonstrated good association between the images and histology, with up to 40% of HGGs functionally presenting a high activity within the non- contrast-enhanced areas in T1. New LINAC technologies, such as intensity-modulated and stereotactic radiotherapy, help to deliver a simultaneous integrated boost(SIB) > 60 Gy. Trials delivering a SIB into a biological GTV showed the feasibility of this treatment, but the final results, in terms of clinical benefits for HGG patients, are still pending. Many issues have been identified: the variety of MRI and PET machines(and amino-acid tracers), the heterogeneity of the protocols used for image acquisition and post-treatment, the geometric distortion and the unreliable algorithms for co-registration of brain anatomy with functional maps, and the semi-quiescent but highly invasive HGG cells. These issues could be solved by the homogenization of the protocols and software applications, the simultaneous acquisition of anatomic and functional images(PET-MRI machines), the combination of complementary imaging tools(perfusion and diffusion MRI), and the concomitant addition of some ad hoc targeted drugs against angiogenesis and invasiveness to chemoradiotherapy. The integration of these hybrid data will construct new synthetic metrics for fully individualized treatments.

Radiation Therapy of Head and Neck Paragangliomas: Experience from Radiotherapy Department at the National Institute of Oncology in Rabat (Morocco)

Background and Purpose: Paragangliomas are rare tumors of the head and neck. Their management remains problematic and varies considerably depending on the center. This study reported 14 years of experience in the management of head and neck paraganglioma (HNPGls). We aimed to assess the therapeutic results of these tumors in terms of local control and overall survival. Materials and Methods: We included 16 patients followed for HNPGls and treated by radiotherapy from January 2006 to June 2018 in the National Institute of Oncology in Rabat. Results: The median age was 44.5 years (15 - 67). 13 patients were female and three male with a sex ratio of 4.3. Cervical mass was the common sign (56.3%). All patients received radiation therapy. This radiation was exclusive in 43.7% of cases or adjuvant to partial surgical resection in 56.3%. The median dose of radiotherapy was 54 Gy (46 - 60) and it was delivered by a three-dimensional conformal radiotherapy technique in 15 patients and volumetric modulated arc therapy in one. There were few acute complications such as grade I and II mucositis and dermatitis. After a median follow-up of 5.6 years (2 - 13.4), local control, defined by radiological stability or regression, was obtained in 14 patients, two patients progressed and one died. Progression-free survival rates at 5 and 7 years were 93.8% and 78.1% respectively, and overall survival at 5 and 7 years was 92.3%. Conclusions: Surgery is the first-line treatment for HNPGls. When surgery is not possible or incomplete, radiotherapy has its place in the therapeutic strategy of this rare disease for long-term local control.

Updates on management of gliomas in the molecular age

Gliomas are primary brain tumors derived from glial cells of the central nervous system,afflicting both adults and children with distinct characteristics and therapeutic challenges.Recent developments have ushered in novel clinical and molecular prognostic factors,reshaping treatment paradigms based on classi-fication and grading,determined by histological attributes and cellular lineage.This review article delves into the diverse treatment modalities tailored to the specific grades and molecular classifications of gliomas that are currently being discussed and used clinically in the year 2023.For adults,the therapeutic triad typically consists of surgical resection,chemotherapy,and radiotherapy.In contrast,pediatric gliomas,due to their diversity,require a more tailored approach.Although complete tumor excision can be curative based on the location and grade of the glioma,certain non-resectable cases demand a chemotherapy approach usually involving,vincristine and carboplatin.Addi-tionally,if surgery or chemotherapy strategies are unsuccessful,Vinblastine can be used.Despite recent advancements in treatment methodologies,there remains a need of exploration in the literature,particularly concerning the efficacy of treatment regimens for isocitrate dehydrogenase type mutant astrocytomas and fine-tuned therapeutic approaches tailored for pediatric cohorts.This review article explores into the therapeutic modalities employed for both adult and pediatric gliomas in the context of their molecular classification.

Radiotherapy delays malignant transformation and prolongs survival in patients with IDH-mutant gliomas

Objective:IDH-mutant lower-grade gliomas(LGGs,grade 2 or 3)eventually transform into secondary grade 4 astrocytomas(sAIDHmut/G4).Here,we sought to describe the transformation time,risk factors,and outcomes in malignant transformation of IDHmutant LGGs.Methods:We screened data for 108 patients with sAIDHmut/G4 in the Chinese Glioma Genome Atlas who had initial IDH-mutant LGGs and underwent reoperation during 2005–2021.We evaluated the transformation time from IDH-mutant LGGs to sAIDHmut/G4,and associated risk factors and outcomes.Malignant transformation was defined as pathological confirmation of grade 4 astrocytoma.Results:The median age of the 108 patients with IDH-mutant LGGs was 35 years(range,19–54);the median age at transformation was 40 years(range,25–62);and the median follow-up time for all patients was 146 months(range,121–171).The average transformation time was 58.8 months for all patients with LGGs(range,5.9–208.1);63.5 and 51.9 months for grade 2 and 3 gliomas,respectively;and 58.4 and 78.1 months for IDH-mutant/1p/19q-non-codeleted astrocytomas and IDH-mutant/1p/19q-codeleted oligodendrogliomas,respectively.Univariate and multivariate analysis indicated that radiotherapy[hazard ratio(HR),0.29;95%confidence interval(CI),0.137–0.595;P=0.001]and non-A blood type(HR,0.37;95%CI,0.203–0.680;P=0.001)were protective factors against delayed malignant transformation.Radiotherapy was associated with improved survival after transformation(HR,0.44;95%CI,0.241–0.803;P=0.008),overall survival(HR,0.50;95%CI,0.265–0.972;P=0.041),and progression-free survival(HR,0.25;95%CI,0.133–0.479;P<0.0001)in patients with IDH-mutant gliomas.Conclusions:Radiotherapy is associated with delayed malignant transformation and improved survival in patients with IDHmutant gliomas.

Conventional radiotherapy followed by IMRT as a boost in combination with chemotherapy treatment for high-grade gliomas:prognostic factors and outcomes

Objective： The aim of the study was to retrospectively evaluate the outcomes and important prognostic factors for patients with high-grade gliomas （HGG） treated with conventional radiotherapy （RT） followed by IMRT as a boost in combination with chemotherapy. Methods： From November 2004 to November 2006, 112 consecutive patients with high-grade gliomas were treated with radiotherapy, which included initial conventional radiotherapy and an IMRT boost to a total dose of 57.5-62.5 Gy, with 27-29 fractions delivered over 37-45 days. All cases received 3-6 cycles of chemotherapy, 63 cases received temozolomide, and another 49 cases received methyI-CCNU and teniposide. The acute and late treatment toxicities and the patterns of treatment failure were recorded. The overall survival （OS） rate and progression-free survival （PFS） rate were calculated, and the prognostic factors were analyzed. Results： Most of the acute radiation reactions were grade 1 or 2. No grade 4 acute reactions were noted. Three cases developed radiation necrosis. Grades Ⅰ, Ⅱ, and Ⅲ myelosuppressions were observed in 5, 32, and 12 cases of 49 patients treated with teniposide and methyl-CCNU, respectively. Grades Ⅰ and Ⅱ myelosuppressions were observed in 15 and 3 of the 63 patients who were treated with temozolomide, respectively. The 57 cases （50.9%） had recurred locally, and 13 cases （11.6%） had intracranial dissemination. The OS rates at 1, 2, and 3 years were 78.9%, 54.7%, and 30.8%, respectively. The PFS rates at 1,2, and 3 years were 63.8%, 38.9%, and 10.5%, respectively. A multivariate analysis showed that only tumor location and KPS were prognostic factors of OS. These same two variables and histopathology were statistically significant predictive factors in a multivariate analysis for PFS. Conclusion： Radiation toxicities were not found to be increased in this retrospective study with 112 consecutive patients of combined modality therapy including an IMRT boost treatment for HGG. Higher rate of local regional dissemination within the brain was observed than before. Tumor location, histopathology and KPS were important prognostic factors.

Stereotactic body radiotherapy in pancreatic adenocarcinoma

Background:Stereotactic body radiotherapy(SBRT)in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue.This review aimed at the SBRT application in the treatment of pancreatic cancer.Data sources:We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022.Keywords used in the search included:“pancreatic adenocarcinoma”OR“pancreatic cancer”AND“stereotactic ablative radiotherapy(SABR)”OR“stereotactic body radiotherapy(SBRT)”OR“chemoradiotherapy(CRT)”.English language articles with information on technical characteristics,doses and fractionation,indications,recurrence patterns,local control and toxicities of SBRT in pancreatic tumors were included.All articles were assessed for validity and relevant content.Results:Optimal doses and fractionation have not yet been defined.However,SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT.Furthermore,the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma.Conclusions:SBRT is an effective modality for patients with pancreatic cancer,supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control.SBRT opens a possibility of improving outcomes for these patients,both in neoadjuvant treatment and with radical intent.

Clinical observation in three-dimensional conformal radiotherapy (3D-CRT) with concurrent chemotherapy in treatment of postoperative cerebral gliomas

Objective:The aim of the study was to investigate the efficacy of three-dimensional conformal radiotherapy (3D-CRT) combined with Temozolomide (TMZ) concurrent chemotherapy in treatment of postoperative cerebral gliomas by prospective randomized controlled trials. Methods: Sixty-two patients with cerebral glioma who had residual tumor were divided into 3D-CRT group (radiotherapy group, n=31) and 3D-CRT with concurrent chemotherapy group (chemoradiotherapy group, n=31) prospectively. All patients received a dose of 50-60 Gy/25-30 F/5-6 weeks by 6 MV-X ray, three-dimensional conformal radiotherapy, 1 f/d, 5 times a week. Chemotherapy regimen was Temozolomide:75 mg/m2/d, concomitantly with radiotherapy, followed by 150-200 mg/m2/d, 5 days, 28 days per cycle, totally 3-6 cycles. Results: The total response rate was 35.3% (11/31) in radiotherapy group. The response rate was 61.3% (19/31) in chemoradiotherapy group. There was significant difference in curative effect (P=0.042). There was no significant difference in survival comparison of two groups (P=0.263). Stratified analysis showed the patients with grade Ⅲ gliomas of chemoradiotherapy group had better prognosis than ones of radiotherapy group (P=0.043). Conclusion: The 3D-CRT with concurrent chemotherapy can improve the survival of cerebral gliomas with pathological grade Ⅲ.

IQGAP3 promotes the progression of glioma as an immune and prognostic marker

Background:IQGAP3 plays a crucial role in regulating cell proliferation,division,and cytoskeletal organization.Abnormal expression of IQGAP3 has been linked to various tumors,but its function in glioma is not well understood.Methods:Various methods,including genetic differential analysis,single-cell analysis,ROC curve analysis,Cox regression,Kaplan-Meier analysis,and enrichment analysis,were employed to analyze the expression patterns,diagnostic potential,prognostic implications,and biological processes involving IQGAP3 in normal and tumor tissues.The impact of IQGAP3 on immune infiltration and the immune microenvironment in gliomas was evaluated using immunofluorescence.Additionally,the cBioPortal database was used to analyze copy number variations and mutation sites of IQGAP3.Experimental validation was also performed to assess the effects of IQGAP3 on glioma cells and explore underlying mechanisms.Results:High IQGAP3 expression in gliomas is associated with an unfavorable prognosis,particularly in wild-type IDH and 1p/19q non-codeleted gliomas.Enrichment analysis revealed that IQGAP3 is involved in regulating the cell cycle,PI3K/AKT signaling,p53 signaling,and PLK1-related pathways.Furthermore,IQGAP3 expression may be closely related to the immunosuppressive microenvironment of glioblastoma.BRD-K88742110 and LY-303511 are potential drugs for targeting IQGAP3 in anti-glioma therapy.In vitro experiments showed that downregulation of IQGAP3 inhibits the proliferation and migration of glioma cells,with the PLK1/PI3K/AKT pathway potentially playing a crucial role in IQGAP3-mediated glioma progression.Conclusion:IQGAP3 shows promise as a valuable biomarker for diagnosis,prognosis,and immunotherapeutic strategies in gliomas.

Present situation and prospect of immunotherapy for unresectable locally advanced esophageal cancer during peri-radiotherapy

Four major studies(Checkmate577,Keynote-590,Checkmate649 and Attraction-4)of locally advanced esophageal cancer published in 2020 have established the importance of immunotherapy,represented by anti-programmed death protein(PD)-1 in postoperative adjuvant treatment and advanced first-line treatment of locally advanced or advanced esophageal cancer and esophagogastric junction cancer,from the aspects of proof of concept,long-term survival,overall survival rate and progression-free survival.For unresectable or inoperable nonmetastatic esophageal cancer,concurrent radiotherapy and chemotherapy is the standard treatment recommended by various guidelines.Because its curative effect is still not ideal,it is necessary to explore radical radiotherapy and chemotherapy in the future,and it is considered to be promising to combine them with immunotherapeutic drugs such as anti-PD-1.This paper mainly discusses how to combine radical concurrent radiotherapy and chemotherapy with immunotherapy for unresectable local advanced esophageal cancer.

Targeting the organelle for radiosensitization in cancer radiotherapy

Radiotherapy is a well-established cytotoxic therapy for local solid cancers, utilizing high-energy ionizing radiation to destroy cancer cells. However, this method has several limitations, including low radiation energy deposition, severe damage to surrounding normal cells, and high tumor resistance to radiation. Among various radiotherapy methods, boron neutron capture therapy (BNCT) has emerged as a principal approach to improve the therapeutic ratio of malignancies and reduce lethality to surrounding normal tissue, but it remains deficient in terms of insufficient boron accumulation as well as short retention time, which limits the curative effect. Recently, a series of radiosensitizers that can selectively accumulate in specific organelles of cancer cells have been developed to precisely target radiotherapy, thereby reducing side effects of normal tissue damage, overcoming radioresistance, and improving radiosensitivity. In this review, we mainly focus on the field of nanomedicine-based cancer radiotherapy and discuss the organelle-targeted radiosensitizers, specifically including nucleus, mitochondria, endoplasmic reticulum and lysosomes. Furthermore, the organelle-targeted boron carriers used in BNCT are particularly presented. Through demonstrating recent developments in organelle-targeted radiosensitization, we hope to provide insight into the design of organelle-targeted radiosensitizers for clinical cancer treatment.

Role of glioma stem cells in promoting tumor chemo- and radioresistance: A systematic review of potential targeted treatments

BACKGROUND Gliomas pose a significant challenge to effective treatment despite advancements in chemotherapy and radiotherapy.Glioma stem cells(GSCs),a subset within tumors,contribute to resistance,tumor heterogeneity,and plasticity.Recent studies reveal GSCs’role in therapeutic resistance,driven by DNA repair mechanisms and dynamic transitions between cellular states.Resistance mechanisms can involve different cellular pathways,most of which have been recently reported in the literature.Despite progress,targeted therapeutic approaches lack consensus due to GSCs’high plasticity.AIM To analyze targeted therapies against GSC-mediated resistance to radio-and chemotherapy in gliomas,focusing on underlying mechanisms.METHODS A systematic search was conducted across major medical databases(PubMed,Embase,and Cochrane Library)up to September 30,2023.The search strategy utilized relevant Medical Subject Heading terms and keywords related to including“glioma stem cells”,“radiotherapy”,“chemotherapy”,“resistance”,and“targeted therapies”.Studies included in this review were publications focusing on targeted therapies against the molecular mechanism of GSC-mediated re-sistance to radiotherapy resistance(RTR).RESULTS In a comprehensive review of 66 studies on stem cell therapies for SCI,452 papers were initially identified,with 203 chosen for full-text analysis.Among them,201 were deemed eligible after excluding 168 for various reasons.The temporal breakdown of studies illustrates this trend:2005-2010(33.3%),2011-2015(36.4%),and 2016-2022(30.3%).Key GSC models,particularly U87(33.3%),U251(15.2%),and T98G(15.2%),emerge as significant in research,reflecting their representativeness of glioma characteristics.Pathway analysis indicates a focus on phosphoinositide 3-kinase/protein kinase B/mammalian target of rapamycin(mTOR)(27.3%)and Notch(12.1%)pathways,suggesting their crucial roles in resistance development.Targeted molecules with mTOR(18.2%),CHK1/2(15.2%),and ATP binding cassette G2(12.1%)as frequent targets underscore their importance in overcoming GSC-mediated resistance.Various therapeutic agents,notably RNA inhibitor/short hairpin RNA(27.3%),inhibitors(e.g.,LY294002,NVP-BEZ235)(24.2%),and monoclonal antibodies(e.g.,cetuximab)(9.1%),demonstrate versatility in targeted therapies.among 20 studies(60.6%),the most common effect on the chemotherapy resistance response is a reduction in temozolomide resistance(51.5%),followed by reductions in carmustine resistance(9.1%)and doxorubicin resistance(3.0%),while resistance to RTR is reduced in 42.4%of studies.CONCLUSION GSCs play a complex role in mediating radioresistance and chemoresistance,emphasizing the necessity for precision therapies that consider the heterogeneity within the GSC population and the dynamic tumor microenvironment to enhance outcomes for glioblastoma patients.