Clinical Benefit with Intraoperative Radiotherapy Combined with Regional Chemotherapy for Advanced Pancreatic Carcinoma

Objective: To evaluate the effectiveness of intraoperative radiotherapy (IORT) in combination with regional chemotherapy in the treatment of advanced pancreatic carcinoma.Methods: 17 patients with advanced pancreatic adenocarcinoma were treated with IORT and regional chemotherapy with 5-FU, Epirubucin and Mitomycin, and 6 cases accepted external radiotherapy postoperatively.Results: 35.29% (6/17) of the patients were clinical benefit responders and 23.53% (4/17) had a partial response. The median survival time was 11 months and the 1-year survival rate was 35.29% (6/17)Conclusion: IORT in combination with regional chemotherapy had a good impact on clinical benefit without severe side effects in locally advanced pancreatic carcinoma and led to a significant prolongation of the survival time. Key words pancreatic cancer - intraoperative radiotherapy - chemotherapy

Analysis of the Long-term Effect of Intraoperative Radiotherapy (IORT) for Non-Small Cell Lung Carcinoma (NSCLC)

OBJECTIVE To analyze the long-term effects of treatment with an op-eration + postoperative irradiation (A group) and an operation+intraoperative radiotherapy+postoperative irradiation (B group) in non-small cell lung cancer patients. METHODS Through a prospective randomized clinical trial, a total of 154 patients with non-small cell lung carcinoma were divided into two groups of 77 cases. Among the 154 cases, there were 134 squamous carcinomas, 17 adenocarcinomas and 3 adeno-squamous carcinomas. TNM staging: there were 17 in StageⅠ, 76 in Stage Ⅱ and 61 in Stage Ⅲ. A dosage of 15～25 Gy IORT, energy 9～16 MeV electrons, was delivered to the tumors. The doses given were 40～60 Gy postoperation. RESULTS The local control rates in A and B groups were 49.4% and 62.3% respectively (P<0.05). The survivals at 3, 5 and 7 years for group A were 40.3%, 27.3%, and 5.2% and for group B 44.2%, 28.6% and 6.5% (P>0.05). There were 16 deaths from radiotherapy complications, with 2 cases in group A and 14 in group B. CONCLUSION IORT+postoperative irradiation can enhance the local control rate of non-small cell lung cancer patients and reduce the recurrent rates, but it can not improve long-term survival.

The role of intraoperative electron radiotherapy in centrally located hepatocellular carcinomas treated with narrow-margin (<1 cm) hepatectomy: a prospective, phase 2 study

Background: Postoperative radiotherapy (RT) is known to play an important role in the treatment of hepatocellular carcinomas (HCCs), but the specific role of intraoperative electron radiotherapy (IOERT) in HCCs remains unclear. The aim of this study was to investigate the safety and efficacy of IOERT in centrally located HCCs treated with narrow-margin (<1 cm) hepatectomy. Methods: This was a single-center, phase 2, prospective non-randomized controlled study, including 268 patients with centrally located HCCs who underwent narrow-margin hepatectomy. The patients were subsequently allocated to the IOERT group (n=59) or to the control group (n=65). The primary outcome of the study was to compare recurrence-free survival (RFS) between the IOERT group and the control group, and the secondary outcome was to compare overall survival (OS) rate between the two groups. Results: Of 268 patients enrolled, a total of 124 were included in the study: 59 in IOERT group, 65 in control group. The 1-, 2-, 3-year RFS rates were 79.3%, 62.1% and 45.8% for patients in the IOERT group, and 47.6%, 28.6%, and 22.9% for patients in the control group, respectively (P=0.025). The 1-, 2-, and 3-year OS rates were 100.0%, 94.9%, and 83.7% for patients in the IOERT group, and 92.3%, 87.5%, and 79.4% for patients in the control group, respectively (P=0.314). Subgroup analysis of MVI (+) patients revealed that RFS and OS are significantly prolonged in the IOERT subgroup as compared to the control, whereas there was no significant difference of RFS and OS between the two groups in MVI (−) patients. Conclusions: IOERT for centrally located HCCs with concurrent narrow-margin hepatectomy was feasible and safe. Statistically better RFS rate was observed in the IOERT group compared to the control group. Subgroup analysis revealed that IOERT was more beneficial for postoperative survival of HCC patients with MVI. Trial Registration: ChiCTR-TRC-12002802;www.who.int/ictrp.

Evaluation of intraoperative radiotherapy for gastric carcinoma with D2 and D3 surgical resection

AIM： TO study the proper sites and doses of intraoperative radiotherapy （IORT） for gastric carcinoma and the effects of this treatment. METHODS： A total of 106 patients with stage Ⅰ -Ⅳ gastric carcinoma who received D2 or D3 radical operation combined with IORT were analyzed. Sixty-seven patients with gastric cancer of the antrum and body underwent distal gastrectomy. The sites of irradiation were at the celiac artery and hepatoduodenal ligment area. Another 39 patients with carcinoma of the cardia and upper part of the gastric body and whole stomach underwent proximal gastrectomy or total gastrectomy. The sites of irradiation for this group were the upper margin of the pancreas and the regional para-aorta. The therapeutic effects （including survival and complications） of these 106 cases received operation combined with IORT （IORT group） were compared with 441 cases treated during the same time period by a radical operation alone （operation group）. RESULTS： The radiation dose below 30 Gy was safe. The therapeutic method of the operation combined with IORT did not prolong the survival of patients with stage Ⅰ and Ⅳ gastric cancer, but the 5-year survival rates of patients with stage Ⅱ and Ⅲ gastric cancers were significantly improved. The 5-year survival rates of the stages Ⅲ cancer patients receiving D2 resection combined with IORT were markedly improved, while for those receiving D3 radical resection, only the postoperative 3- or 4-year survival rates were improved （P 〈 0.005-0.001）. The 5-year survival rate for those patients was raised only by 4.7% （P 〉 0.05）. CONCLUSION： The 5-year survival rates of patients with stages Ⅱ and Ⅲ gastric carcinoma who received D2 lymphadenectomy combined with IORT were improved, and there was no influence on the postoperative complications and mortality.

Efficacy and safety of intraoperative radiotherapy in rectal cancer:A systematic review and meta-analysis

BACKGROUND In recent years,intraoperative radiotherapy(IORT)has been increasingly used for the treatment of rectal cancer.However,the efficacy and safety of IORT for the treatment of rectal cancer are still controversial.AIM To evaluate the value of IORT for patients with rectal cancer.METHODS We searched PubMed,Embase,Cochrane Library,Web of Science databases,and conference abstracts and included randomized controlled trials and observational studies on IORT vs non-IORT for rectal cancer.Dichotomous variables were evaluated by odds ratio(OR)and 95%confidence interval(CI),hazard ratio(HR)and 95%CI was used as a summary statistic of survival outcomes.Statistical analyses were performed using Stata V.15.0 and Review Manager 5.3 software.RESULTS In this study,3 randomized controlled studies and 12 observational studies were included with a total of 1460 patients,who are mainly residents of Europe,the United States,and Asia.Our results did not show significant differences in 5-year overall survival(HR=0.80,95%CI=0.60-1.06;P=0.126);5-year disease-free survival(HR=0.94,95%CI=0.73-1.22;P=0.650);abscess(OR=1.10,95%CI=0.67-1.80;P=0.713),fistulae(OR=0.79,95%CI=0.33-1.89;P=0.600);wound complication(OR=1.21,95%CI=0.62-2.36;P=0.575);anastomotic leakage(OR=1.09,95%CI=0.59-2.02;P=0.775);and neurogenic bladder dysfunction(OR=0.69,95%CI=0.31-1.55;P=0.369).However,the meta-analysis of 5-year local control was significantly different(OR=3.07,95%CI=1.66-5.66;P=0.000).CONCLUSION The advantage of IORT is mainly reflected in 5-year local control,but it is not statistically significant for 5-year overall survival,5-year disease-free survival,and complications.

Intraoperative radiotherapy:principles and prospects

Intraoperative radiotherapy （IORT） in its broadest sense refers to the delivery of radiation at the time of an opera- tion. It includes multiple techniques, namely intraoperative electron irradiation, intraoperative brachytherapy and intraopera- rive photon irradiation. It has a wide range of existing and potentially enlarging clinical applications. We will discuss in this review the rationale for and use of intraoperative irradiation in conjunction with surgical exploration with or without external- beam irradiation （EBRT） and chemotherapy.

Dose Distributions in Simulated Electron Radiotherapy with Intraoral Cones Using Treatment Planning System

Aim: This study aims to evaluate the difference between depth data from an intraoral cone and a conventional irradiation tube calculated using a treatment planning system (TPS), and that measured using an intraoral cone for electron radiotherapy. Background: A TPS is only compatible with conventional irradiation tubes. However, such systems are not suitable for determining dose distributions when a special cone is employed. Materials and Methods: Dose distributions were calculated using the beam data for mounted intraoral cones using a TPS. Then, the dose distribution by field size was calculated for a low-melting-point lead alloy using the beam data for a mounted conventional tube. The calculated data were evaluated against the measured intraoral-cone depth data based on the dose and depth differences. Results: The calculated data for the intraoral cone case did not match the measured data. However, the depth data obtained considering the field size determined for the lead alloy using the conventional tube were close to the measured values for the intraoral cone case. The difference in the depth at which the absorbed dose was 50% of the maximum value of the percentage depth dose was less than ±4 mm for the generalized Gaussian pencil beam convolution algorithm and less than ±1 mm for the electron Monte Carlo algorithm. Conclusion: It was found that the measured and calculated dose distributions were in agreement, especially when then electron Monte Carlo algorithm was used. Thus, the TPS can be employed to determine dose distributions for intraoral cone applications.

Mammographic Findings Associated with Accelerated Partial Breast Irradiation Using Single Fraction Intraoperative Radiotherapy

Purpose: To evaluate the mammographic findings of women treated with accelerated partial breast irradiation (APBI) using single-fraction intraoperative radiotherapy (IORT). Materials/Methods: Women ≥ 40 years of age with unifocal invasive or intraductal carcinoma ≤ 2.5 cm on physical examination, mammography, and ultrasound were enrolled on an APBI trial using single fraction IORT. Post-treatment mammographic imaging was obtained at 6 months, 1 year, and then annually. Results: Between 12/02 and 6/04, 17 women underwent IORT at the time of lumpectomy (median age = 60 years;range = 40 - 83). The initial post-IORT mammogram showed increased density at the lumpectomy site in 11 patients (65%), while six patients (35%) had architectural distortion in the area of the irradiated tissue. Fifteen patients (88%) had numerous punctate, benign-appearing calcifications corresponding to the irradiated region. There was focal skin thickening near the incision in 13 patients (76%). At a median of 67 months, architectural distortion had stabilized and the benign-appearing calcifications remained stable in number and character. Eight patients (47%) had mammographic findings consistent with fat necrosis, ranging in size from 0.5 - 4 cm. Conclusions: After lumpectomy and IORT, mammographic changes include increased density and benign appearing calcifications in the irradiated region with focal skin thickening. These changes appear to stabilize over time and are consistent with post-treatment changes. These changes are important to identify in order to characterize benign changes from recurrent tumor.

Experience with intraoperative radiotherapy for breast cancer: the Geneva University Hospital's experience

Background Breast conserving surgery along with adjuvant radiotherapy is effective in terms of local control and survival for early- stage breast cancer （1）. External beam radiotherapy （EBRT） following breast conserving surgery has been shown to improve survival by preventing local recurrence, in the Early Breast Cancer Trialists＇ Collaborative Group meta-analysis （2）. Standard radiotherapy typically requires numerous fractions over a 3-5 week period and is performed weeks or months after surgery or chemotherapy.

A Dosimetric Comparison of Radiotherapy Techniques in the Treatment of Carcinoma of Breast

Objectives of present study are a) to compare the planning and delivery aspects of five different techniques, planned by a) forward, inverse planning and electronic tissue compensation methods;and b) to evaluate and verify the accuracy of the planning system using phantom to estimate the skin dose for target and contraletral breast from five techniques. In-vivo skin dosimetry is planned with TL detectors. Five different radiotherapy techniques for treatment of carcinoma breast were studied using archived computed tomography (CT) scans of 25 breast conserving surgery patients (leftsided whole breast), planned for 50 Gy in 25 fractions. Linear accelerator (Clinac 2300 CD) photon beams were used and thermoluminescent detectors (TLD) [LiF:Mg, Ti] estimated dose on humanoid phantom. Dose coverage (95%) (to PTV) and hot spot (105%) covering volumes did not show differences (p > 0.05) in all 5 plans;Electronic compensator plans are better than others. IP-IMRT plan showed the worst Homogeneity Index (HI) (p < 0.05) and needed more monitor units (MU) (437 ± 84), than other techniques. The mean doses to ipsi-lateral lung, contra-lateral breast (CB) and heart OARs (V20 ipsi.lung, CB, V30 Heart,) are the least with IP-IMRT. IP-IMRT and E-COMP plans resulted in significantly lower mean dose to the superficial skin (Dmean, V40skin, 45skin, 50skin) (p < 0.05). The mean doses estimated by TLDs were comparable or higher in 3D-CRT (D) and 3D-CRT (P) for PTV and CB;less for IP-IMRT and E-COMP compared to TPS. IP-IMRT and E-COMP techniques provide good target coverage, low doses to OARs, the least doses to the skin of PTV and contra-lateral breast and less hot spots;E-COMP showed better homogeneity, fewer MUs, and the least dose in non-target zones.

A study on Fricke-PVA-xylenol orange hydrogel dosimeter for E-beam radiotherapy

A Fricke-PVA-xylenol orange (FPX) hydrogel dosimeter, in good transparency, was prepared by physical crosslinking for three-dimensional dose measurements. The process of mixing the chemical dosimeter with the PVA solution was carried out at room temperature, which reduced the influence of auto-oxidation rate. Gradation in color was obviously observed with different distance from the radiation source after 6 MeV electron beam irradiation for radiotherapy. The effects of irradiation dose and three components of the FPX gel dosimeter, i.e. ferrous ions, xylenol orange (XO) and sulphuric acid on sensitivity and stability of dose response were investigated by UV-vis spectropho-tometric measurement. The dose response of the FPX gel dosimeter was linear in the range 0~2.0 Gy. The orthogonal test was employed to find the optimal composition of the gel dosimeter with a sensitivity of about 0.095 cm-1·Gy-1. It was found that XO concentration greatly affected the sensitivity of dose response and lower concentrations of the ferrous ion and XO gave higher sensitivity within the range 0~2.0 Gy.

Long-term outcomes of intraoperative radiotherapy for early-stage breast cancer in China: amulticenter real-world study

Dear Editor,Intraoperative radiotherapy(IORT)is an accelerated par-tial breast irradiation(APBI)treatment that is accom-plished intraoperatively.Numerous clinical trials indicate that IORT is safe and effective,non-inferior to standard whole-breast external beam radiotherapy(EBRT)for low-risk patients who receive breast-conserving surgery[1-3].Nevertheless,these studies mainly included non-Asians and thus lack adequate evidence to support the value of IORT in Asian patients with breast cancer.

A compact X-band backward traveling-wave accelerating structure

Very high-energy electrons(VHEEs)are potential candidates for FLASH radiotherapy for deep-seated tumors.We proposed a compact VHEE facility based on an X-band high-gradient high-power technique.In this study,we investigated and realized the first X-band backward traveling-wave(BTW)accelerating structure as the buncher for a VHEE facility.A method for calculating the parameters of single cell from the field distribution was introduced to simplify the design of the BTW structure.Time-domain circuit equations were applied to calculate the transient beam parameters of the buncher in the unsteady state.A prototype of the BTW structure with a thermionic cathode-diode electron gun was designed,fabricated,and tested at high power at the Tsinghua X-band high-power test stand.The structure successfully operated with 5-MW microwave pulses from the pulse compressor and outputted electron bunches with an energy of 8 MeV and a pulsed current of 108 mA.

胸部肿瘤三维适形调强放疗摆位误差相关因素分析

分析胸部肿瘤患者行三维适形调强放疗(IMRT)时产生摆位误差的相关因素,以准确计算出临床靶区(CTV)外放边界(摆位扩边(SM)值),从而实现安全放疗.以莆田学院附属医院接受IMRT治疗的83例胸部恶性肿瘤患者为研究对象,应用体位固定技术及电子射野影像装置(EPID)测量比较胸部恶性肿瘤IMRT的摆位误差,采用多元线性回归分析方法对摆位误差相关因素进行分析,进而分类计算出其SM值.结果显示,83例受试者在X轴、Y轴、Z轴上的SM值分别为0.31、0.28、0.28 cm;靶区定位、性别及肺容量分别为Y轴个体随机误差、Z轴个体系统误差、Z轴个体随机误差的独立影响因素.这表明肿瘤患者行IMRT治疗时靶区定位、性别及肺容量在不同方向上影响其摆位误差.

外阴癌膀胱截石位电子线放疗支架在体位固定中的临床价值分析

目的探讨外阴癌膀胱截石位电子线放疗支架在体位固定中的临床价值。方法选取32例外阴癌患者,随机分为两组,各16例。两组均行膀胱截石位电子线放疗,对照组采用传统放疗摆位,研究组采用放疗支架进行摆位。比较两组摆位误差、照射野中心偏移距离、计划靶区(PTV)剂量学指标[适形指数(CI)、均匀性指数(HI)]、放疗疗效、摆位舒适度。结果研究组X轴、Y轴、Z轴摆位误差均小于对照组(P<0.05);研究组照射野中心偏移距离小于对照组(P<0.05);研究组CI、HI与对照组比较,均有显著性差异(P<0.05);研究组缓解率(87.50%)与对照组(81.25%)比较,差异无统计学意义(P>0.05);研究组摆位舒适度(93.75%)高于对照组(56.25%)(P<0.05)。结论外阴癌膀胱截石位电子线放疗支架能有效提高摆位准确度和患者舒适度,同时能降低照射野中心偏移距离,提高放疗照射剂量精准性,具有推广应用价值。

Intraoperative Radiation Therapy(INTRABEAM)Experience at the Mastology Unit Leopoldo Aguerrevere Clinic

Introduction: External radiation therapy has been the fundamental pillar when treating breast cancer. Partial radiation therapy and intraoperative radiation treatment have created modifications that allow the irradiation of the breast to be performed at the surgical act delivering a single large fraction or a “boost” dose directly at the tumor bed. We will discuss patients treated with INTRABEAM (Carl Zeiss Surgical Oberkochen, Germany) at the “Mastology Unit at Leopoldo Aguerrevere Clinic”. Materials and Methods: The selection of patients is crucial for the success of the treatment, same protocol of treatment has been applied to every patient at the surgical act. Since September 2013 until February 2015, we have treated a total of 148 patients with the INTRABEAM unit, we will discuss the 114 patients treated by the team at the “Mastology Unit at Leopoldo Aguerrevere Clinic” with ages between 31 and 87 years in which 46% were single treatments and 54% were treated as a “boost” for external radiation therapy. Results: The procedure has been well tolerated with only a 17% of transient fibrosis and a 12% of seromas. We have had none mayor complications like dehiscence of the wound or necrosis of the borders. Conclusion: With this preliminary presentation, we would like to demonstrate that the technique and protocol used at our mastology unit with the intraoperative radiation treatment is safe and has many advantages to the patients including better comfort, cost-effective and with results comparable to external radiotherapy.

医用电子直线加速器技术现状与发展趋势

70%以上的肿瘤患者需要接受放射治疗,而医用电子直线加速器是肿瘤放射治疗的重要高端放疗设备。随着现代人工智能技术在医用电子直线加速器中的应用,放疗技术已从当初的普通放疗发展为如今的智慧放疗。该研究描述了医用电子直线加速器的发展历程、工作原理与系统构成,概述了束流调控、多叶光栅、引导定位技术、剂量测评等医用电子直线加速器关键技术,并展望了生物引导放疗、FLASH闪疗、智慧放疗等前沿放疗技术的发展趋势,为医用电子直线加速器的技术发展提供参考。

Bolus材质对乳腺癌胸壁电子束放疗剂量分布的影响

目的:评估组织等效物Bolus材质对乳腺癌术后胸壁电子束放疗剂量分布的影响。方法:构建乳腺癌改良根治术后胸壁放疗模型,基于国际原子能机构(IAEA)官网中6 MeV电子束相空间文件(PSF)和Geant4蒙特卡罗应用软件包,计算Bolus材质中水、聚苯乙烯、聚乳酸、甘油和硅胶5种不同材质电子束放疗胸部剂量分布,对比胸壁和肺组织中剂量分布差异。结果:Bolus材质对电子束在胸壁的最大剂量深度(d_(max))影响较小,10 mm厚的Bolus所致d_(max)最大差异约2 mm;对剂量分布产生影响较大,尤其在胸壁后缘和浅表肺组织中,胸壁后缘剂量由大到小对应Bolus材质依次为聚苯乙烯、水、聚乳酸、硅胶和甘油,对于5 mm和10 mm厚的Bolus材质,剂量差异分别约为8%和15%;浅表肺组织中剂量由大到小对应Bolus材质依次是水、聚苯乙烯、聚乳酸、硅胶和甘油,对于5 mm和10 mm厚的Bolus材质,剂量差异最大分别可达约50%和70%。结论:Bolus材质对胸壁电子束放疗剂量分布所产生影响较大,合理选择Bolus材质有助于保证靶区剂量,减少肺组织中剂量沉积。

乳腺癌放射治疗研究现状

乳腺癌是女性常见恶性肿瘤之一,在女性恶性肿瘤中发病率居于首位,给女性的生命健康带来了严重威胁。目前,针对乳腺癌的治疗包括外科手术治疗、放射治疗、化学治疗、内分泌治疗、免疫治疗、靶向治疗和姑息治疗等多种方式。放射治疗在乳腺癌治疗中扮演着不可或缺的角色,在不同治疗阶段对乳腺癌患者实施针对性的放射治疗,能显著提升临床治疗效果,提高患者生存率,有效抑制癌症复发,同时缓解患者症状,提升生活质量,进而不断优化乳腺癌放射相关的治疗策略。

Is current clinical practice modified about intraoperative breast irradiation?

After the results obtained in the two randomized clinical trial, the ELIOT trial and the TARGIT-A trial, a heated debate is going on concerning the question of applying intraoperative radiotherapy （IORT） instead of postoperative whole breast irradiation （WBI） after breast conservative treatment. Currently, many centers are applying the IORT following the strict selection criteria dictated by the working groups American Society for Radiation Ontology （ASTRO） and Groupe Europeen de Curietherapie-European Society for Therapeutic Radiology and Oncology （GEC-ESTRO） and monitoring the oncological outcome together with radiation toxicity on breast tissue. The clinical experience of the Geneva University Hospital regarding the use of the Intrabeam system is evaluated and compared with current evidences.