Combinational therapy with Myc decoy oligodeoxynucleotides encapsulated in nanocarrier and X-irradiation on breast cancer cells

The Myc gene is the essential oncogene in triple-negative breast cancer(TNBC).This study investigates the synergistic effects of combining Myc decoy oligodeoxynucleotides-encapsulated niosomes-selenium hybrid nanocarriers with X-irradiation exposure on the MDA-MB-468 cell line.Decoy and scramble ODNs for Myc transcription factor were designed and synthesized based on promoter sequences of the Bcl2 gene.The nanocarriers were synthesized by loading Myc ODNs and selenium into chitosan(Chi-Se-DEC),which was then encapsulated in niosome-nanocarriers(NISM@Chi-Se-DEC).FT-IR,DLS,FESEM,and hemolysis tests were applied to confirm its characterization and physicochemical properties.Moreover,cellular uptake,cellular toxicity,apoptosis,cell cycle,and scratch repair assays were performed to evaluate its anticancer effects on cancer cells.All anticancer assessments were repeated under X-ray irradiation conditions(fractionated 2Gy).Physicochemical characteristics of niosomes containing SeNPs and ODNs showed that it is synthesized appropriately.It revealed that the anticancer effect of NISM@Chi-Se-DEC can be significantly improved in combination with X-ray irradiation treatment.It can be concluded that NISM@Chi-Se-DEC nanocarriers have the potential as a therapeutic agent for cancer treatment,particularly in combination with radiation therapy and in-vivo experiments are necessary to confirm the efficacy of this nano-drug.

Selective internal radiation therapy segmentectomy:A new minimally invasive curative option for primary liver malignancies?

Transarterial radioembolization or selective internal radiation therapy(SIRT)has emerged as a minimally invasive approach for the treatment of tumors.This percutaneous technique involves the local,intra-arterial delivery of radioactive microspheres directly into the tumor.Historically employed as a palliative measure for liver malignancies,SIRT has gained traction over the past decade as a potential curative option,mirroring the increasing role of radiation segmentectomy.The latest update of the BCLC hepatocellular carcinoma guidelines recognizes SIRT as an effective treatment modality comparable to other local ablative methods,particularly well-suited for patients where surgical resection or ablation is not feasible.Radiation segmentectomy is a more selective approach,aiming to deliver high-dose radiation to one to three specific hepatic segments,while minimizing damage to surrounding healthy tissue.Future research efforts in radiation segmentectomy should prioritize optimizing radiation dosimetry and refining the technique for super-selective administration of radiospheres within the designated hepatic segments.

Unraveling the efficacy network: A network meta-analysis of adjuvant external beam radiation therapy methods after hepatectomy

BACKGROUND Primary liver cancer is a malignant tumor with a high recurrence rate that significantly affects patient prognosis.Postoperative adjuvant external radiation therapy(RT)has been shown to effectively prevent recurrence after liver cancer resection.However,there are multiple RT techniques available,and the differ-ential effects of these techniques in preventing postoperative liver cancer re-currence require further investigation.AIM To assess the advantages and disadvantages of various adjuvant external RT methods after liver resection based on overall survival(OS)and disease-free survival(DFS)and to determine the optimal strategy.METHODS This study involved network meta-analyses and followed the PRISMA guidelines.The data of qualified studies published before July 10,2023,were collected from PubMed,Embase,the Web of Science,and the Cochrane Library.We included relevant studies on postoperative external beam RT after liver resection that had OS and DFS as the primary endpoints.The magnitudes of the effects were determined using risk ratios with 95%confidential intervals.The results were analyzed using R software and STATA software.RESULTS A total of 12 studies,including 1265 patients with hepatocellular carcinoma(HCC)after liver resection,were included in this study.There was no significant heterogeneity in the direct paired comparisons,and there were no significant differences in the inclusion or exclusion criteria,intervention measures,or outcome indicators,meeting the assumptions of heterogeneity and transitivity.OS analysis revealed that patients who underwent stereotactic body radiotherapy(SBRT)after resection had longer OS than those who underwent intensity modulated radiotherapy(IMRT)or 3-dimensional conformal RT(3D-CRT).DFS analysis revealed that patients who underwent 3D-CRT after resection had the longest DFS.Patients who underwent IMRT after resection had longer OS than those who underwent 3D-CRT and longer DFS than those who underwent SBRT.CONCLUSION HCC patients who undergo liver cancer resection must consider distinct advantages and disadvantages when choosing between SBRT and 3D-CRT.IMRT,a RT technique that is associated with longer OS than 3D-CRT and longer DFS than SBRT,may be a preferred option.

Dosimetric Comparative Analysis of Volumetric Modulated Arc Therapy and Intensity-Modulated Radiation Therapy in Cervical Cancer

Objective:To carry out dosimetric comparison between volumetric modulated arc therapy(VMAT)and intensity-modulated radiation therapy(IMRT)in cervical cancer.Methods:50 postoperative cervical cancer patients were included in this study.The patients were admitted for treatment from January 2021 to January 2022.VMAT and IMRT plans were designed for each patient to analyze the dose distribution in the target area of the two treatment techniques.Results:Comparing the monitor unit for single treatment(638.21±116.21 MU)and time of single treatment(143.21±23.14 s)in the observation group and the monitor unit for single treatment(932.14±74.11 MU)and time of single treatment(223.14±17.26 s)in the control group,there was significant difference(P<0.05);there was also significant difference(P<0.05)between the normal tissue(bladder and rectum)of the observation group and that(bladder and rectum)of the control group.Conclusion:VMAT is more effective in cervical cancer,and it has a certain protective effect on normal tissues in patients and can reduce the radiation dose.

Establishment of a prediction model for severe acute radiation enteritis associated with cervical cancer radiotherapy

BACKGROUND Cervical cancer is one of the most common gynecological malignant tumors.Radiation enteritis(RE)leads to radiotherapy intolerance or termination of radiotherapy,which negatively impacts the therapeutic effect and seriously affects the quality of life of patients.If the incidence of RE in patients can be predicted in advance,and targeted clinical preventive treatment can be carried out,the side effects of radiotherapy in cervical cancer patients can be significantly reduced.Furthermore,accurate prediction of RE is essential for the selection of individualized radiation dose and the optimization of the radiotherapy plan.AIM To analyze the relationships between severe acute RE(SARE)of cervical cancer radiotherapy and clinical factors and dose-volume parameters retrospectively.METHODS We included 50 cervical cancer patients who received volumetric modulated arc therapy(VMAT)from September 2017 to June 2018 in the Department of Radiotherapy at The First Affiliated Hospital Soochow University.Clinical and dose-volume histogram factors of patients were collected.Logistic regression analysis was used to evaluate the predictive value of each factor for SARE.A nomogram to predict SARE was developed(SARE scoring system≥3 points)based on the multiple regression coefficients;validity was verified by an internal verification method.RESULTS Gastrointestinal and hematological toxicity of cervical cancer VMAT gradually increased with radiotherapy and reached the peak at the end of radiotherapy.The main adverse reactions were diarrhea,abdominal pain,colitis,anal swelling,and blood in the stool.There was no significant difference in the incidence of gastrointestinal toxicity between the radical and postoperative adjuvant radiotherapy groups(P>0.05).There were significant differences in the small intestine V_(20),V_(30),V_(40),and rectal V40 between adjuvant radiotherapy and radical radiotherapy after surgery(P<0.05).Univariate and multivariate analyses revealed anal bulge rating(OR:14.779,95%CI:1.281-170.547,P=0.031)and disease activity index(DAI)score(OR:53.928,95%CI:3.822-760.948,P=0.003)as independent predictors of SARE.CONCLUSION Anal bulge rating(>0.500 grade)and DAI score(>2.165 points)can predict SARE.The nomogram shows potential value in clinical practice.

Comprehensive Treatment Uncertainty Analysis and PTV Margin Estimation for Fiducial Tracking in Robotic Liver Stereotactic Body Radiation Therapy

Objective This study aims to quantify the uncertainties of CyberKnife Synchrony fiducial tracking for liver stereotactic body radiation therapy(SBRT)cases,and evaluate the required planning target volume(PTV)margins.Methods A total of 11 liver tumor patients with a total of 57 fractions,who underwent SBRT with synchronous fiducial tracking,were enrolled for the present study.The correlation/prediction model error,geometric error,and beam targeting error were quantified to determine the patient-level and fraction-level individual composite treatment uncertainties.The composite uncertainties and multiple margin recipes were compared for scenarios with and without rotation correction during treatment.Results The correlation model error-related uncertainty was 4.3±1.8,1.4±0.5 and 1.8±0.7 mm in the superior-inferior(SI),left-right,and anterior-posterior directions,respectively.These were the primary contributors among all uncertainty sources.The geometric error significantly increased for treatments without rotation correction.The fraction-level composite uncertainties had a long tail distribution.Furthermore,the generally used 5-mm isotropic margin covered all uncertainties in the left-right and anterior-posterior directions,and only 75%of uncertainties in the SI direction.In order to cover 90%of uncertainties in the SI direction,an 8-mm margin would be needed.For scenarios without rotation correction,additional safety margins should be added,especially in the superior-inferior and anterior-posterior directions.Conclusion The present study revealed that the correlation model error contributes to most of the uncertainties in the results.Most patients/fractions can be covered by a 5-mm margin.Patients with large treatment uncertainties might need a patient-specific margin.

Effect of Stereotactic Body Radiation Therapy on Diverse Organ Lesions in Advanced Non-Small Cell Lung Cancer Patients Receiving Immune Checkpoint Inhibitors

Objective The combination of stereotactic body radiation therapy(SBRT)and immune checkpoint inhibitors(ICIs)is actively being explored in advanced non-small-cell lung cancer(NSCLC)patients.However,little is known about the optimal fractionation and radiotherapy target lesions in this scenario.This study investigated the effect of SBRT on diverse organ lesions and radiotherapy dose fractionation regimens on the prognosis of advanced NSCLC patients receiving ICIs.Methods The medical records of advanced NSCLC patients consecutively treated with ICIs and SBRT were retrospectively reviewed at our institution from Dec.2015 to Sep.2021.Patients were grouped according to radiation sites.Progression-free survival(PFS)and overall survival(OS)were recorded using the Kaplan-Meier method and compared between different treatment groups using the log-rank(Mantel-Cox)test.Results A total of 124 advanced NSCLC patients receiving ICIs combined with SBRT were identified in this study.Radiation sites included lung lesions(lung group,n=43),bone metastases(bone group,n=24),and brain metastases(brain group,n=57).Compared with the brain group,the mean PFS(mPFS)in the lung group was significantly prolonged by 13.3 months(8.5 months vs.21.8 months,HR=0.51,95%CI:0.28–0.92,P=0.0195),and that in the bone group prolonged by 9.5 months with a 43%reduction in the risk of disease progression(8.5 months vs.18.0 months,HR=0.57,95%CI:0.29–1.13,P=0.1095).The mPFS in the lung group was prolonged by 3.8 months as compared with that in the bone group.The mean OS(mOS)in the lung and bone groups was longer than that of the brain group,and the risk of death decreased by up to 60%in the lung and bone groups as compared with that of the brain group.When SBRT was concurrently given with ICIs,the mPFS in the lung and brain groups were significantly longer than that of the bone group(29.6 months vs.16.5 months vs.12.1 months).When SBRT with 8–12 Gy per fraction was combined with ICIs,the mPFS in the lung group was significantly prolonged as compared with that of the bone and brain groups(25.4 months vs.15.2 months vs.12.0 months).Among patients receiving SBRT on lung lesions and brain metastases,the mPFS in the concurrent group was longer than that of the SBRT→ICIs group(29.6 months vs.11.4 months,P=0.0003 and 12.1 months vs.8.9 months,P=0.2559).Among patients receiving SBRT with<8 Gy and 8–12 Gy per fraction,the mPFS in the concurrent group was also longer than that of the SBRT→ICIs group(20.1 months vs.5.3 months,P=0.0033 and 24.0 months vs.13.4 months,P=0.1311).The disease control rates of the lung,bone,and brain groups were 90.7%,83.3%,and 70.1%,respectively.Conclusion The study demonstrated that the addition of SBRT on lung lesions versus bone and brain metastases to ICIs improved the prognosis in advanced NSCLC patients.This improvement was related to the sequence of radiotherapy combined with ICIs and the radiotherapy fractionation regimens.Dose fractionation regimens of 8–12 Gy per fraction and lung lesions as radiotherapy targets might be the appropriate choice for advanced NSCLC patients receiving ICIs combined with SBRT.

Evaluation of 3D-CRT and VMAT Radiotherapy Plans for Left Breast Cancer with Regional Lymph Nodes Irradiation

Introduction: Radiation therapy after breast surgery is an integral part of the treatment of early breast cancer. The goal of radiation therapy is to achieve the best possible coverage of the planning target volume (PTV), while reducing the dose to organs at risk (OARs) which are normal tissues whose sensitivity to irradiation could cause damage that can lead to modification of the treatment plan. In the last decade, radiation oncologist started to use the Intensity Modulated Radiotherapy (IMRT) and Volumetric Modulated Arc Therapy (VMAT) for irradiating the breast, in order to achieve better dose distribution and target dose to the PTV and OAR. The aim of this study is to compare 2 external radiotherapy techniques (VMAT vs 3D) for patients with node-positive left breast cancer. Patients and Methods: We randomly selected 10 cases of postoperative radiotherapy for breast cancer in our hospital. The patients are all female, the average age was 45.4 years old, and the primary lesions are left breast. The ANOVA test was used to compare the mean difference between subgroups, and the p value Results: Dose volume histogram (DVH) was used to analyze each evaluation dose of clinical target volume (CTV) and organs at risk (OARs). Compared to 3DCRT plans, VMAT provided more uniform coverage to the breast and regional lymph nodes. The max point dose for tVMAT was lower on average (106.4% for VMAT versus 109% for 3DCRT). OAR sparing was improved with tVMAT, with a lower average V17Gy for the left lung (27.91% for VMAT versus 30.04% for 3DCRT, p and lower for V28Gy (13.75% for VMAT versus 22.34% for 3DCRT, p = 0.01). We also found a lower V35Gy for the heart on VMAT plan (p = 0.02). On the contrary, dose of contralateral breast was lower in 3DCRT than VMAT (0.59 Gy vs 3.65 Gy, p = 0.00). Conclusion: The both types of plans can meet the clinical dosimetry demands of postoperative radiotherapy for left breast cancer. The VMAT plan has a better conformity, but 3CDRT can provide a lower dose to the contralateral organs (breast and lung) to avoid the risk of secondary cancers.

Three-dimensional conformal intensity-modulated radiation therapy of left femur foci does not damage the sciatic nerve

During radiotherapy to kill femoral hydatid tapeworms, the sciatic nerve surrounding the focus can be easily damaged by the treatment. Thus, it is very important to evaluate the effects of ra- diotherapy on the surrounding nervous tissue. In the present study, we used three-dimensional, conformal, intensity-modulated radiation therapy to treat bilateral femoral hydatid disease in Meriones meridiani. The focus of the hydatid disease on the left femur was subiected to radio- therapy （40 Gy） for 14 days, and the right femur received sham irradiation. Hematoxylin-eosin staining, electron microscopy, and terminal deoxynucleotidyl transferase-dUTP nick end labeling assays on the left femurs showed that the left sciatic nerve cell structure was normal, with no ob- vious apoptosis after radiation. Trypan blue staining demonstrated that the overall protoscolex structure in bone parasitized with Echinococcus granulosus disappeared in the left femur of the animals after treatment. The mortality of the protoscolex was higher in the left side than in the right side. The succinate dehydrogenase activity in the protoscolex in bone parasitized with Echi- nococcus granulosus was lower in the left femur than in the right femur. These results suggest that three-dimensional conformal intensity-modulated radiation therapy achieves good therapeutic effects on the secondary bone in hydatid disease in Meriones meridiani without damaging the morphology or function of the sciatic nerve.

A prospective trial of volumetric intensity-modulated arc therapy vs conventional intensity modulated radiation therapy in advanced head and neck cancer

AIM: To prospectively compare volumetric intensitymodulated arc therapy(VMAT) and conventional intensity-modulated radiation therapy(IMRT) in coverage of planning target volumes and avoidance of multiple organs at risk(OARs) in patients undergoing definitive chemoradiotherapy for advanced(stage Ⅲ or Ⅳ)squamous cell cancer of the head and neck. METHODS: Computed tomography scans of 20 patients with advanced tumors of the larynx, naso-, oroand hypopharynx were prospectively planned using IMRT(7 field) and VMAT using two arcs. Calculated doses to planning target volume(PTV) and OAR were compared between IMRT and VMAT plans. Dose-volume histograms(DVH) were utilized to obtain calculated doses to PTV and OAR, including parotids, cochlea,spinal cord, brainstem, anterior tongue, pituitary and brachial plexus. DVH's for all structures were compared between IMRT and VMAT plans. In addition the planswere compared for dose conformity and homogeneity. The final treatment plan was chosen by the treating radiation oncologist. RESULTS: VMAT was chosen as the ultimate plan in 18 of 20 patients(90%) because the plans were thought to be otherwise clinically equivalent. The IMRT plan was chosen in 2 of 20 patients because the VMAT plan produced concentric irradiation of the cord which was not overcome even with an avoidance structure. For all patients, VMAT plans had a lower number of average monitor units on average(MU = 542.85) than IMRT plans(MU = 1612.58)(P < 0.001). Using the conformity index(CI), defined as the 95% isodose volume divided by the PTV, the IMRT plan was more conformal with a lower conformity index(CI = 1.61) than the VMAT plan(CI = 2.00)(P = 0.003). Dose homogeneity, as measured by average standard deviation of dose distribution over the PTV, was not different with VMAT(1.45 Gy) or IMRT(1.73 Gy)(P = 0.069). There were no differences in sparing organs at risk.CONCLUSION: In this prospective study, VMAT plans were chosen over IMRT 90% of the time. Compared to IMRT, VMAT plans used only one third of the MUs, had shorter treatment times, and similar sparing of OAR. Overall, VMAT provided similar dose homogeneity but less conformity in PTV irradiation compared to IMRT. This difference in conformity was not clinically significant.

Comparison of efficacy and safety between late-course and simultaneous integrated dose-increasing intensity-modulated radiation therapy for cervical cancer complicated with pelvic lymph node metastasis

Objective This study aimed to compare and analyze the clinical efficacy and safety of late-course and simultaneous integrated dose-increasing intensity-modulated radiation therapy(IMRT) for cervical cancer complicated with pelvic lymph node metastasis. Methods Sixty patients with cervical cancer complicated with pelvic lymph node metastasis who were admitted to our hospital from January 2013 to January 2015 were enrolled. The patients were randomly divided into the late-course dose-increasing IMRT group and the simultaneous integrated dose-increasing IMRT group, with 30 cases included in each group, respectively. All patients were concurrently treated with cisplatin. After treatment, the clinical outcomes of the two groups were compared. Results The remission rate of symptoms in the simultaneous integrated dose-increasing IMRT group was significantly higher than that in the late-course dose-increasing IMRT group(P < 0.05). The follow-up results showed that the overall survival time, progression-free survival time, and distant metastasis time of patients in the simultaneous integrated dose-increasing IMRT group were significantly longer than those in the late-course dose-increasing IMRT group(P < 0.05). The recurrent rate of lymph nodes in the radiation field in the simultaneous integrated dose-increasing IMRT group was significantly lower(P < 0.05) than in the late-course dose-increasing IMRT group. There was no significant difference in the incidence of cervical and vaginal recurrence and distant metastasis between the two groups(P > 0.05). The radiation doses of Dmax in the small intestine, D1 cc(the minimum dose to the 1 cc receiving the highest dose) in the bladder, and Dmax in the rectum in the simultaneous integrated dose-increasing IMRT group were significantly lower(P < 0.05) than in the late-course dose-increasing IMRT group. There was no significant difference in intestinal D2 cc(the minimum dose to the 2 cc receiving the highest dose) between the two groups(P > 0.05). The incidence of bone marrow suppression in the simultaneous integrated dose-increasing IMRT group was significantly lower(P < 0.05) than in the late-course dose-increasing IMRT group.Conclusion The application of simultaneous integrated dose-increasing IMRT in the treatment of cervical cancer patients complicated with pelvic lymph node metastasis can significantly control tumor progression, improve the long-term survival time, and postpone distant metastasis time with high safety.

Treatment outcomes for different subgroups of nasopharyngeal carcinoma patients treated with intensity-modulated radiation therapy

Although many studies have investigated intensity-modulated radiation therapy (IMRT) for nasopharyngeal carcinoma (NPC),sample sizes in the reported studies are usually small and different in outcomes in different T and N subgroups are seldom analyzed.Herein,we evaluated the outcomes of NPC patients treated with IMRT and further explored treatment strategy to improve such outcome.We collected clinical data of 865 NPC patients treated with IMRT alone or in combination with chemotherapy,and classified all cases into the following prognostic categories according to different TNM stages:early stage group (T1-2N0-1M0),advanced local disease group (T3-4N0-1M0),advanced nodal disease group (T1-2N2-3M0),and advanced locoregional disease group (T3-4N2-3M0).The 5-year overall survival (OS),local relapse-free survival (LRFS),and distant metastases-free survival (DMFS) were 83.0%,90.4%,and 84.0%,respectively.The early disease group had the lowest treatment failure rate,with a 5-year OS of 95.6%.The advanced local disease group and advanced nodal disease group had similar failure pattern and treatment outcomes as well as similar hazard ratios for death (4.230 and 4.625,respectively).The advanced locoregional disease group had the highest incidence of relapse and death,with a 5-year DMFS and OS of 62.3% and 62.2%,respectively,and a hazard ratio for death of 10.402.Comparing with IMRT alone,IMRT in combination with chemotherapy provided no significant benefit to locoregionally advanced NPC.Our results suggest that the decision of treatment strategy for NPC patients should consider combinations of T and N stages,and that IMRT alone for early stage NPC patients can produce satisfactory results.However,for advanced local,nodal,and locoregional disease groups,a combination of chemotherapy and radiotherapy is recommended.

Intensity-modulated radiation therapy with concurrent chemotherapy for locally advanced cervical and upper thoracic esophageal cancer

AIM: To evaluate the dosimetry, efficacy and toxicity of intensity-modulated radiation therapy (IMRT) and concurrent chemotherapy for patients with locally advanced cervical and upper thoracic esophageal cancer. METHODS: A retrospective study was performed on 7 patients who were definitively treated with IMRT and concurrent chemotherapy. Patients who did not receive IMRT radiation and concurrent chemotherapy were not included in this analysis. IMRT plans were evaluated to assess the tumor coverage and normal tissue avoidance. Treatment response was evaluated and toxicities were assessed. RESULTS: Five- to nine-beam IMRT were used to deliver a total dose of 59.4-66 Gy (median: 64.8 Gy) to the primary tumor with 6-MV photons. The minimum dose received by the planning tumor volume (PTV) of the gross tumor volume boost was 91.2%-98.2% of the prescription dose (standard deviation [SD]: 3.7%-5.7%). The minimum dose received by the PTV of the clinical tumor volume was 93.8%-104.8% (SD: 4.3%-11.1%) of the prescribed dose. With a median follow-up of 15 mo (range: 3-21 mo), all 6 evaluable patients achieved complete response. Of them, 2 developed localrecurrences and 2 had distant metastases, 3 survived with no evidence of disease. After treatment, 2 patients developed esophageal stricture requiring frequent dilation and 1 patient developed tracheal-esophageal fi stula. CONCLUSION: Concurrent IMRT and chemotherapy resulted in an excellent early response in patients with locally advanced cervical and upper thoracic esophageal cancer. However, local and distant recurrence and toxicity remain to be a problem. Innovative approaches are needed to improve the outcome.

Impact of prolonged fraction dose-delivery time modeling intensity-modulated radiation therapy on hepatocellular carcinoma cell killing

AIM: To explore the impact of prolonged fraction dosedelivery time modeling intensity-modulated radiation therapy (IMRT) on cell killing of human hepatocellular carcinoma (HCC) HepG2 and Hep3B cell lines.METHODS: The radiobiological characteristics of human HCC HepG2 and Hep3b cell lines were studied with standard clonogenic assays, using standard linear-quadratic model and incomplete repair model to fit the dose-survival curves. The identical methods were also employed to investigate the biological effectiveness of irradiation protocols modeling clinical conventional fractionated external beam radiotherapy (EBRT, fraction delivery time 3 min) and IMRT with different prolonged fraction delivery time (15, 30, and 45 min). The differences of cell surviving fraction irradiated with different fraction delivery time were tested with paired t-test. Factors determining the impact of prolonged fraction delivery time on cell killing were analyzed.RESULTS: The α/β and repair half-time (T1/2) of HepG2and Hep3b were 3.1 and 7.4 Gy, and 22 and 19 min respectively. The surviving fraction of HepG2 irradiated modeling IMRT with different fraction delivery time was significantly higher than irradiated modeling EBRT and the cell survival increased more pronouncedly with the fraction delivery time prolonged from 15 to 45 min,while no significant differences of cell survival in Hep3b were found between different fraction delivery time protocols.CONCLUSION: The prolonged fraction delivery time modeling IMRT significantly decreased the cell killing in HepG2 but not in Hep3b. The capability of sub-lethal damage repair was the predominant factor determining the cell killing decrease. These effects, if confirmed by clinical studies, should be considered in designing IMRT treatments for HCC.

Local definitive intensity-modulated radiation therapy recommended for patients initially diagnosed with nasopharyngeal carcinoma with distant metastasis after an effective systemic chemotherapy

Objective The aim of the study was to propose a hypothesis that local definitive intensity-modulated radiation therapy(IMRT) should be recommended for initially diagnosed metastatic nasopharyngeal carcinoma(NPC) and demonstrate its feasibility.Methods Recently published papers on local definitive radiotherapy for initially diagnosed metastatic NPC were reviewed to propose a hypothesis.Results Several studies revealed the survival benefits of adding local definitive radiotherapy to the systemic chemotherapy in patients initially diagnosed with metastatic NPC.Conclusion We suggested that local definitive IMRT should be recommended in patients initially diagnosed with NPC with distant metastasis after an effective systemic chemotherapy, which may possibly prolong their survival time and potentially treat the disease.

The Impact of Variation in Bladder Volume on the Doses of Target and Organ-at-Risk in Intensity-Modulated Radiation Therapy for Localized Prostate Cancer

Intensity-modulated radiation therapy (IMRT) has become the mainstay of treatment for localized prostate cancer. In IMRT, minimizing differences between the conditions used during planning CT and daily treatment is important to prevent adverse events in normal tissues. In the present study, we evaluated the impact of variation in bladder volume on the doses to various organs. A total of 35 patients underwent definitive radiotherapy at Saitama Medical Center. A Light Speed RT16 (GE Healthcare) was used for planning and to obtain examination CT images. Such images were acquired after 4 - 6 days of planning CT image acquisition. The IMRT plans were optimized using the planning CT data to satisfy the dose constraints set by our in-house protocols for the PTV and the OARs. The dose distributions were then re-calculated using the same IMRT beams, and checked on examination CT images. It was clear that bladder volume affected the doses to certain organs. We focused on the prostate, bladder, rectum, small bowel, and large bowel. Regression coefficients were calculated for variables that correlated strongly with bladder volume (p < 0.05). We found that variation in bladder volume [cm3] predicted deviations in the bladder V70Gy, V50Gy, and V30Gy [%];the maximum dose to the small bowel [cGy];and the maximum dose to the large bowel [cGy]. The regression coefficients were -0.065, -0.125, -0.180, -10.22, and -9.831, respectively. We evaluated the impacts of such variation on organ doses. These may be helpful when checking a patient’s bladder volume before daily IMRT for localized prostate cancer.

The Reproducibility of Patient Setup for Head and Neck Cancers Treated with Image-Guided and Intensity-Modulated Radiation Therapies Using Thermoplastic Immobilization Device

The reproducibility of patient setup is an important issue for head and neck cancers treated with intensity-modulated radiation therapy (IMRT). In this study, an image-guided radiation therapy (IGRT) system has been used to minimize the uncertainty of patient setup while standard thermoplastic masks were used to provide adequate immobilization for the head and neck. However, they do not provide sufficient immobilization of the shoulders, which is an important requirement in comprehensive nodal irradiation. Therefore, we investigated the setup and rotational shifts in head and neck cancer patients undergoing IMRT for which this immobilization device had been used together with an IGRT system. The setup and rotational shifts of patients were analyzed using the ExacTrac X-ray 6D IGRT system. The patients were classified as having head and neck tumors in the upper or lower regions. The upper neck nodes included lymph nodal level II while the lower neck nodes included lymph nodal levels III and IV. Clinical data from 227 treatment sessions of 12 head and neck cancer patients were analyzed. The random translational error in inter-and intra-fraction errors of the anterio-posterior (AP) direction might influence the rotational errors of pitch and roll in the upper region. At the same time, the random translational error in the inter-and intra-fraction errors of the AP direction might influence the rotational error of roll in the lower region. We believe that these random translational errors should be considered during treatment. We found variability in random translational errors for different regions in the anatomy of head and neck cancer patients due to rotational shifts. Depending on the location of the primary lesion or the selected nodal treatment targets, these relative positional variations should be considered when setup and rotational shifts are corrected with IGRT systems before treatment.

Prostate specific antigen bounce after intensity-modulated radiation therapy in an Asian population

Objective:Serum prostate specific antigen(PSA)is commonly used to evaluate treatment response after definitive radiation therapy(RT).However,PSA levels can temporarily rise without a clear reason,termed“PSA bounce”,and often engender great anxiety for both patients and physicians.The present study aimed to determine the prevalence and factors that predict“PSA bounce”after intensity-modulated radiation therapy(IMRT),and the relevance to biochemical failure and cancer recurrence in an Asian population.Methods:We retrospectively reviewed 206 patients who received IMRT for prostate cancer from 2004 to 2012 in the National Cancer Centre Singapore.These patients were followed up with regular PSA monitoring.We defined“PSA bounce”as a rise of 0.1 ng/mL,followed by two consecutive falls.Patients with biochemical failure(PSA nadir t 2 ng/mL)were further evaluated for cancer recurrence.Results:Sixty-one patients(29.6%)experienced“PSA bounce”,at a median time of 16 months and lasted for 12 months.Age remained the most consistent predictor of the incidence,duration and extent of“PSA bounce”.Other contributory factors included baseline PSA,Gleason score and PSA nadir.Hormonal therapy and prostate volume did not affect this phenomenon.Sixteen patients(7.8%)developed biochemical recurrence,at median time of 32 months,of which 11 were confirmed to have metastatic disease.The median follow-up time was 71 months.

Effect of Tegafur Gimeracil Oteracil Potassium Capsule + Kangai injection + intensity-modulated radiation therapy on the cellular malignant biological processes in advanced cervical cancer lesion

Objective:To study the effect of Tegafur Gimeracil Oteracil Potassium Capsule + Kangai injection + intensity-modulated radiation therapy on the cellular malignant biological processes in advanced cervical cancer lesion.Methods: Patients who were diagnosed with advanced cervical cancer in the Second People Hospital of Banan District Chongqing between April 2015 and March 2017 were selected and divided into two groups, group A received Tegafur Gimeracil Oteracil Potassium Capsule + Kangai injection + intensity-modulated radiation therapy, and group B received cisplatin + intensity-modulated radiation therapy. Serum contents of tumor markers, tumor invasion molecules and tumor proliferation molecules of two groups of patients were detected before treatment as well as 2 weeks and 4 weeks after treatment.Results: Serum E-cad, STMN1, Fas and p53 levels of both groups of patients 2 weeks and 4 weeks after treatment were significantly higher than those before treatment while TSGF, TK1, SCC-Ag, CA125, OPN, MMP9, NGAL, CyclinE, CyclinD1 and PCNA levels were significantly lower than those before treatment, and serum E-cad, STMN1, Fas and p53 levels of group A 2 weeks and 4 weeks after treatment were significantly higher than those of group B while TSGF, TK1, SCC-Ag, CA125, OPN, MMP9, NGAL, CyclinE, CyclinD1 and PCNA levels were significantly lower than those of group B.Conclusion: Tegafur Gimeracil Oteracil Potassium Capsule + Kangai injection + intensity-modulated radiation therapy for advanced cervical cancer can induce cancer cell apoptosis and inhibit cancer cell proliferation and invasion.

Evaluating the influence of 6 MV and 15 MV photon beams on prostate intensity-modulated radiation therapy plans

Objective We aimed to determine the effects of low- and high-energy intensity-modulated radiation therapy(IMRT) photon beams on the target volume planning and on the critical organs in the case of prostate cancer. Methods Thirty plans were generated by using either 6 MV or 15 MV beams separately, and a combination of both 6 and 15 MV beams. All plans were generated by using suitable planning objectives and dose constraints, which were identical across the plans, except the beam energy. The plans were analyzed in terms of their target coverage, conformity, and homogeneity, regardless of the beam energy. Results The mean percentage values of V_(70 Gy) for the rectal wall for the plans with 6 MV, 15 MV, and mixedenergy beams were 16.9%, 17.8%, and 16.4%, respectively, while the mean percentage values of V_(40 Gy) were 53.6%, 52.3%, and 50.4%. The mean dose values to the femoral heads for the 6 MV, 15 MV, and mixed-energy plans were 30.1 Gy, 25.5 Gy, and 25.4 Gy, respectively. The mean integral dose for the 6 MV plans was 10% larger than those for the 15 MV and mixed-energy plans. Conclusion These preliminary results suggest that mixed-energy IMRT plans may be advantageous with respect to the dosimetric characteristics of low- and high-energy beams. Although the reduction of dose to the organs at risk may not be clinically relevant, in this study, IMRT plans using mixed-energy beams exhibited better OAR sparing and overall higher plan quality for deep-seated tumors.