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Combining oncolytic virus and Radiation therapy for cancer management

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Journal of Cancer Metastasis and Treatment 2022年第1期8卷 459-475页

作者： Vito Filbert Jayalie Sri Mutya Sekarutami Department of radiation Oncology Faculty of Medicine Universitas Indonesia-Dr.Cipto Mangunkusumo HospitalJakarta 10430Indonesia

Cancer has caused a tremendous burden in developing countries.Oncolytic virus(OV)therapy is an emerging modality with the potential to be a single or combination agent with Radiation therapy(RT).Following entry of OV to the cell,OV will replicate and assemble before exiting from tumor cells.Construction of OV can be done by modifying the capsid,genome,and chemical material of viruses.Irradiation will induce double-strand breaks,and further integration of OV with DNA damage response pathway will interact with the MRE11-Rad50-Nbs1 complex to regulate the mobilization of E4 open reading frame 6,protein phosphatase 2A,poly(ADP-ribose)polymerase,apoptosis-inducing factor,and topoisomerase-IIβ-binding protein 1.Degradation of DNA-dependent protein kinase catalytic subunits via human simplex virus-1-infected cell polypeptide 0 will inhibit DNA repair.OV and RT have a synergistic interaction to cause viral oncolysis and upregulation of immune response.In the clinical setting,most studies have demonstrated that OV is a safe treatment with less toxicity.Moreover,OV+RT resulted in longer median survival(62.4 vs.37.7 weeks)in malignant glioma.

关键词： Oncolytic virus Radiation therapy cancer developing country

Factors Predicting Late Rectal Disorders after radiation therapy for Prostate Cancer

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Chinese Medical Journal 2017年第20期130卷 2441-2446页

作者： Toshiya Maebayashi Naoya Ishibashi Takuya Aizawa Masakuni Sakaguchi Hideki Sato Katsuhiko Sato Tsuyoshi Matsui Kenya Yamaguchi Satoru Takahashi Department of Radiology Nihon University School of Medicine Tokyo 173-8610 Japan Department of Gastroenterology and Hepatology Nihon University School of Medicine Tokyo 173-8610 Japan Department of Urology Nihon University School of Medicine Tokyo 173-8610 Japan

Background： Although various studies have been conducted on the effects of Radiation therapy for prostate cancer, rectal toxicity after Radiation therapy for prostate cancer, which is an important late adverse event associated with Radiation therapy, has not been sufficiently examined. This study aimed to assess the associations of late rectal disorder （LRD） with dosimetric, anatomic, and clinical factors in patients with prostate cancer who underwent three-dimensional conformal Radiation therapy （3D-CRT）. Methods： We retrospectively analyzed 104 patients undergoing 3D-CRT between January 2009 and October 2011. Thirty patients were administered anticoagulation/antiplatelet （AC/AP） agents. The standard dose was 74 Gy. Uni- and multi-va,iate analyses we,e performed to identify factors predictive of LRD after 3D-CRT. Results： The median follow-up period was 66 （range： 14 87） months. LRD occurred in 10.6% （11/104） of patients. The median time fi＇om RT to LRD was 15 months （range： 7MI months）. Sixty-four percent of those with LRD （7/11 patients） had been given AC/AP agents. Fitly-five （6/11 ） patients had severe internal iliac artery calcification. By univariate analysis, significant predictors of LRD were internal iliac artery calcification, administration of AC/AP agents, and age. Being very elderly was the significant predictor identified by multivariate analysis （P = 0.0276）. For patients receiving AC/AP agents and those with severe internal iliac artery calcification, the LRD incidences were 23.3% （7/30 patients） and 23.1% （6/26 patients）, respectively, and being 75 years of age or older was a significant predictor in these subsets. Conclusions： Our results suggest advanced age, administration of AC/AP agents, and severe internal iliac artery calcification to be risk factors tbr LRD in patients undergoing standard RT. Therefore, it is necessary to administer radiation with particular caution in the very elderly, especially those receiving AC/AP agents and/or with severe internal iliac artery calcification.

关键词： Anticoagulation/Antiplatelet Agents Late Rectal Disorder Prostate Cancer Radiation therapy Severe Internal lliac Artery Calcification

Making Radiation therapy more effective in the era of precision medicine

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Precision Clinical Medicine 2020年第4期3卷 272-283页

作者： Xingchen Peng Zhigong Wei Leo E.Gerweck Department of radiation Oncology Massachusetts General HospitalHarvard Medical SchoolBostonMA 02114USA Department of Biotherapy Cancer CenterWest China HospitalSichuan UniversityChengdu 610041China

Cancer has become a leading cause of death and constitutes an enormous burdenworldwide.radiation is a principle treatment modality used alone or in combination with other forms of therapy,with 50%–70%of cancer patients receiving radiotherapy at some point during their illness.It has been suggested that traditional radiotherapy(daily fractions of approximately 1.8–2 Gy over several weeks)might select for radioresistant tumor cell sub-populations,which,if not sterilized,give rise to local treatment failure and distant metastases.Thus,the challenge is to develop treatment strategies and schedules to eradicate the resistant subpopulation of tumorigenic cells rather than the predominant sensitive tumor cell population.With continued technological advances including enhanced conformal treatment technology,radiation oncologists can increasinglymaximize the dose to tumors while sparing adjacent normal tissues,to limit toxicity and damage to the latter.Increased dose conformality also facilitates changes in treatment schedules,such as changes in dose per treatment fraction and number of treatment fractions,to enhance the therapeutic ratio.For example,the recently developed large dose per fraction treatment schedules(hypofractionation)have shown clinical advantage over conventional treatment schedules in some tumor types.Experimental studies suggest that following large acute doses of radiation,recurrent tumors,presumably sustained by the most resistant tumor cell populations,may in fact be equally or more radiation sensitive than the primary tumor.In this review,we summarize the related advances in radiotherapy,including the increasing understanding of the molecular mechanisms of radioresistance,and the targeting of thesemechanisms with potent small molecule inhibitors,whichmay selectively sensitize tumor cells to radiation.

关键词： Radiation therapy conventional fractionation hypofractionation cancer stem cell cancer treatment

Long-term changes in mandibular bone microchemical quality after Radiation therapy and underlying systemic malignancy:A pilot study

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Journal of Innovative Optical Health Sciences 2021年第6期4卷 90-101页

作者： A.Palander H.Dekker M.Hyvärinen L.Rieppo I.Lyijynen E.A.J.M.Schulten C.M.Ten Bruggenkate A.Koistinen A.Kullaa M.J.Turunen Institute of Dentistry University of Eastern Finland P.O.Box 162770211 KuopioFinland Department of Oral and Maxillofacial Surgery/Oral Pathology Amsterdam University Medical Centers and Academic Centre for Dentistry Amsterdam(ACTA)Vrije Universiteit Amsterdam De Boelelaan 11171081 HV AmsterdamThe Netherlands Research Unit of Medical Imaging Physics and Technology University of Oulu P.O.Box 5000 FI-90014 University of OuluFinland SIB Labs University of Eastern Finland P.O.Box 162770211 KuopioFinland Educational Dental Clinic Kuopio University Hospital P.O.Box 162770211 KuopioFinland Department of Applied Physics University of Eastern Finland P.O.Box 162770211 KuopioFinland

Radiation therapy(RT)is a treatment option for head and neck cancer(HNC),but 2%of RT patients may experience damage to the jawbone,resulting in osteoradionecrosis(ORN).The ORN can manifest years after RT exposure.Changes in the local microchemical bone quality prior to the clinical manifestation of ORN could play a key role in ORN pathogenesis.Chemical bone quality can be analyzed using Fourier transform infrared spectroscopy(FTIR),that is applied to examine the effects of cancer,chemotherapy,and RT on the quality of human man-dibular bone.Cortical mandibular bone samples were harvested from dental implant beds of 23 individuals,i.e.,patients with surgically and radiotherapeutically treated HNC(RT-HNC,n=7),surgically and radiochemotherapeutically treated HNC(CH-RT-HNC,n=3),only surgically treated HNC(SRG-HNC,n=4),and healthy controls(n=9).Infrared spectra were acquired from two representative regions of interest in cortical mandibular bone.Spectral parameters,i.e.,mineral-to-matrix ratio(MM),carbonate-to-matrix ratio(CM),carbonate-to-phosphate ratio(CP),collagen maturity(cross-linking),crystallinity,acid phosphate substitu-tion(APS),and advanced glycation end products(AGEs),were analyzed for each sample.Amide I region of the CH-RT-HNC group differed from the control group in cluster analysis(p=0.02).Apart from a minor variation trend in collagen maturity(p=0.07),there were no other signif-icant differences between the groups.Thus,the effect of radiochemotherapy on mandibular bone composition should be further investigated.In future trials,this study design is potential when the effects of the cancer burden and different HNC treatment modalities on jawbone composition are studied,in order to reveal ORN pathogenesis.

关键词： Mandibular bone Radiation therapy Fourier transform infrared spectroscopy

Radiation therapy in Keloids Treatment： History, Strategy,Effectiveness, and Complication

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Chinese Medical Journal 2017年第14期130卷 1715-1721页

作者： Jing Xu Elan Yang Nan-Ze YU Xiao Long Peking Union Medical College Beijing 100730 China Department of Plastic Surgery Peking Union Medical College Hospital Beijing 100730 China

Objective：Radiation therapy combined with surgical excision was considered as one of the most effective treatment plans for keloid lesions.However,there was no unanimity found over present literatures regarding the issue on optimized treatment strategy for keloids.We here provide a comprehensive review over this issue and emphasize on the influencing factors.Data Sources：The data analyzed in this review were searched from articles included in PubMed and EMBASE databases.Study Selection：The original articles and critical reviews discussing the application of Radiation therapy in keloids treatment were selected for this review.Results：The application of Radiation therapy has transitioned from simple superficial X-ray irradiation to brachytherapy.Furthermore,several factors including radiation type,dose,fraction,interval,and complications were reviewed,and the results revealed that these factors were significant toward clinical outcome at various levels.Conclusions：Both past and present evidence support the idea that combination therapy of radiation and surgical therapy is safe and feasible.However,the optimization of treatment strategy was based on different radiation types and should take dose,fractions,interval,and complications into consideration,which will then decrease the rate of recurrence and increase the level of satisfaction.

关键词： Combination therapy： Keloids Radiation therapy

Short-course or long-course Radiation therapy as a part of a neoadjuvant regimen for stage Ⅱ & Ⅲ rectal adenocarcinoma?

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Chinese Journal of Cancer Research 2019年第6期31卷 849-852页

作者： Nan Zhao Christopher J Lin Fei Wang Chi Lin Department of radiation Oncology University of Nebraska Medical Center OmahaNE 68198USA University of Southern California Los Angeles CA 90007USA

The aim of this mini-review is to compare and contrast the pros and cons of short-course and long-course neoadjuvant chemoRadiation therapy regimens for stageⅡ&Ⅲrectal adenocarcinoma.Multiple trials have demonstrated the equal efficacy and safety of short-course and long-course Radiation therapy as a part of neoadjuvant regimens.Published data also shows that total neoadjuvant therapy could be more successful than neoadjuvant chemoradiation followed by adjuvant chemotherapy.This review points out future research directions for patients with locally advanced rectal adenocarcinoma such as comparing total neoadjuvant therapy that contains a short-course of Radiation therapy to the standard of care,and evaluating how the sequence of short-course Radiation therapy and chemotherapy in the total neoadjuvant therapy impacts the pathological complete response(pCR)rate,local control,and survival outcomes.

关键词： Short-course long-course Radiation therapy rectal cancer

Androgen-deprivation therapy alone versus combined with Radiation therapy or chemotherapy For nonlocalized prostate cancer： a systematic review and meta-analysis

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Asian Journal of Andrology 2016年第1期18卷 102-107页

作者： Jun-Hao Lei Liang-Ren Liu Qiang Wei Tu-Run Song Lu Yang Yang Meng Ping Han Department of Urology West China Hospital Sichuan University Guoxue Xiang #37 Chengdu 610041 Sichuan China

In this paper, we reviewed the long-term survival outcomes, safety, and quality-of-life of androgen-deprivation therapy （ADT） alone versus combined with Radiation therapy （RT） or chemotherapy for locally advanced and metastatic prostate cancer （PCa）. A literature search was performed using OvidSP. Randomized controlled trials （RCTs） that met the following criteria were included： including locally advanced or metastatic PCa, comparing ADT alone versus combined with any treatment method and reporting quantitative data of disease control or survival outcomes. Finally, eight RCTs met the inclusion criteria. Among these, three compared ADT versus ADT plus RT （n = 2344） and one compared ADT versus ADT plus docetaxel-estramustine （n = 413） in locally advanced PCa; two compared ADT versus ADT plus docetaxel （n = 1175） and two compared ADT versus ADT plus estramustine （n = 114） in metastatic PCa. For locally advanced PCa, the addition of RT to long-term ADT can improve the outcomes of survival and tumor control with fully acceptable adverse effects. Specially, the pooled odds ratio （OR） of overall survival （OS） was 1.43 （95% confidence interval 1.20-1.71） when compared ADT plus RT with ADT alone （P 〈 0.0001）. For metastatic hormonally sensitive PCa, the concurrent use of docetaxel plus ADT was effective and safe （pooled OR of OS： 1.29 [1.01-1.65]： P = 0.04）. In all, long-term ADT plus RT and long-term ADT plus docetaxel should be considered as proper treatment option in locally advanced and metastatic hormonally sensitive PCa, respectively. The major limitation for the paper was that only eight RCTs were available.

关键词： androgen-deprivation chemotherapy prostate cancer quality-of-life Radiation therapy

Favorable response after Radiation therapy for intraductal papillary mucinous neoplasms manifesting as acute recurrent pancreatitis:A case report

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World Journal of Clinical Cases 2022年第30期10卷 11116-11121页

作者： Ayaka Harigai Kiyoshi Kume Noriyoshi Takahashi So Omata Rei Umezawa Keiichi Jingu Atsushi Masamune Department of radiation Oncology Tohoku University Graduate School of MedicineSendai 980-8574Japan Division of Gastroenterology Tohoku University Graduate School of MedicineSendai 980-8574Japan

BACKGROUND There has been an increasing number of elderly patients with intraductal papillary mucinous neoplasm(IPMN),who are surgically intolerant and require less invasive treatment options,which are limited.In the present study,we report a case of IPMN presenting with acute recurrent pancreatitis(ARP),in which Radiation therapy effectively prevented further attacks of ARP and reduced tumor volume.CASE SUMMARY An 83-year-old man was referred to our hospital with an asymptomatic incidental pancreatic cyst.Endoscopic ultrasound imaging and magnetic resonance cholangiopancreatography revealed a multiloculated tumor in the head of the pancreas,with dilated pancreatic ducts and mural nodules.The patient was diagnosed with mixed-type IPMN,and five years later,he developed ARP.Several endoscopic pancreatic ductal balloon dilatations failed to prevent further ARP attacks.Surgery was considered clinically inappropriate because of his old age and comorbidities.He was referred to our department for Radiation therapy targeted at those lesions causing intraductal hypertension and radiation was administered at a dose of 50 Gy.An magnetic resonance imaging scan taken ten weeks after treatment revealed a decrease in tumor size and improvement of pancreatic duct dilatation.Fourteen months later,he remains symptom-free from ARP.CONCLUSION This case highlights the important role of Radiation therapy in mitigating the signs and symptoms of ARP in patients with inoperable IPMN.

关键词： Intraductal papillary mucinous neoplasm Acute recurrent pancreatitis Pancreas Radiation therapy Case report

Particle therapy for cancers:a new weapon in Radiation therapy

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Frontiers of Medicine 2012年第2期6卷 165-172页

作者： Guo-Liang Jiang Department of radiation Oncology Fudan University Shanghai Cancer CenterShanghai 200032China

Particle irradiation started to draw attention in the past decade and has now become a hotspot in the radiation oncology community.This article reviews the most advanced developments in particle irradiation,focusing on the characteristics of proton and carbon ions in radiation physics and radiobiology.The Bragg peak of physical dose distribution causes proton and carbon beams to optimally meet the requirement for cancer irradiation because the Bragg peak permits the accurate concentration of the dose on the tumor,thus sparing the adjacent normal tissues.Moreover,carbon ion has more radiobiological benefits than photon and proton beams.These benefits include stronger sterilization effects on intrinsic radio-resistant tumors and more effective killing of hypoxic,G0,and S phase cells.Compared with the most advanced radiation techniques using photon,such as three-dimensional conformal Radiation therapy and intensity-modulated Radiation therapy,proton therapy has yielded more promising outcomes in local control and survival for head and neck cancers,prostate carcinoma,and pediatric cancers.Carbon therapy in Japan showed even more promising results than proton therapy.The local controls and overall survivals were as good as that treated by surgery in early stages of non-small cell lung cancer,hepatocellular carcinoma,prostate carcinoma,and head and neck cancers,especially for such highly resistant tumors as melanoma.The non-invasive nature of particle therapy affords more patients with chances to receive and benefit from treatment.Particle therapy is gradually getting attention from the oncology community.However,the cost of particle therapy facilities has limited the worldwide use of this technology.

关键词： Radiation therapy particle therapy proton carbon cancer