Monte Carlo dose calculations of shielding disks with different material combinations in intraoperative electron radiation therapy (IOERT)

PurposeShielding disks play an important role in intraoperative electron radiation therapy, and different designs are currently used in clinical practice. This paper investigates the dosimetric impact of the shielding disk used during intraoperative electron radiation therapy (IOERT).Materials and MethodsThis paper focuses on the study of four shielding disks types that have been used in our clinic: Aluminum (Al)/Lead (Pb), PMMA/Copper(Cu)/PMMA, Aluminum (Al)/Copper (Cu) and Aluminum (Al)/Steel with their specific thicknesses. The theoretical study was conducted with the EGSnrc Monte Carlo (MC) code. On the other hand, the measurements were carried out with gafchromic films for the four shielding disks for the same setup inside the water phantom. Finally, a comparison of the simulated and measured PDD curves was performed for the four material combinations.ResultsMC simulation and gafchromic measurements illustrated that dose values under the four shielding disks types were close to 0, whereas the backscattering enhancement of the disks were 103% with Al/Pb shielding disk, 102% with Al/Steel shielding disk, 102% with Al/Cu shielding disk, 95% with PMMA/Cu/PMMA shielding disk. The PDDs values of the gafchromic films in front of the disks were: 107%, 105%, 104%, and 94% for the Al/Pb, Al/Steel, Al/Cu, and PMMA/Cu/PMMA disks respectively.ConclusionsThe dose values above and under the shielding disks were acceptable for the four studied shielding types. Demonstrated it is possible to use any of them clinically, while the best shielding disk was the Al/Pb since it has minimum thickness and a small backscatter enhancement.     

Long-term results of intraoperative presacral electron boost radiotherapy (IOERT) in combination with total mesorectal excision (TME) and chemoradiation in patients with locally advanced rectal cancer

BACKGROUND: We analyzed the long-term results of patients with locally advanced rectal cancer using a multimodal approach consisting of total mesorectal excision (TME), intraoperative electron-beam radiation therapy (IOERT), and pre- or postoperative chemoradiation (CRT). PATIENTS AND METHODS: Between 1991 and 2003, 210 patients with locally advanced rectal cancer (65 International Union Against Cancer [UICC] Stage II, 116 UICC Stage III, and 29 UICC Stage IV cancers) were treated with TME, IOERT, and preoperative or postoperative CHT. A total of 122 patients were treated postoperatively; 88 patients preoperatively. Preoperative or postoperative fluoropyrimidine-based CRT was applied in 93% of these patients. RESULTS: Median age was 61 years (range, 26-81). Median follow-up was 61 months. The 5-year actuarial overall survival (OS), disease-free survival (DFS), local control rate (LC), and distant relapse free survival (DRS) of all patients was 69%, 66%, 93%, and 67%, respectively. Multivariate analysis revealed that UICC stage and resection status were the most important independent prognostic factors for OS, DFS, and DRS. The resection status was the only significant factor for local control. T-stage, tumor localization, type of resection, and type of chemotherapy had no significant impact on OS, DFS, DRS, and LC. Acute and late complications > or =Grade 3 were seen in 17% and 13% of patients, respectively. CONCLUSION: Multimodality treatment with TME and IOERT boost in combination with moderate dose pre- or postoperative CRT is feasible and results in excellent long-term local control rates in patients with intermediate to high-risk locally advanced rectal cancer.     

The role of intraoperative radiation therapy (IORT) in the treatment of locally advanced gynecologic malignancies

The prognosis in women with locally advanced primary or recurrent gynecologic malignancies is rather poor. Doses of external beam radiation necessary to treat gross or microscopic recurrence among patients surgically treated or previously irradiated exceed what is tolerated by normal structures. In this group of patients, intraoperative radiation therapy (IORT) can be utilized to maximize local tumor control, minimizing the radiation exposure of dose-limiting surrounding structures. Review of the available literature indicates that IORT may improve long-term local control and overall survival in women with pelvic sidewall and/or para-aortic nodal recurrence. The most encouraging results have been reported in the cases of microscopic residual disease, following surgical debulking.     

Clinical physics, applicator choice, technique, and equipment for electron intraoperative radiation therapy

IORT has been a widely used modality since the 1980s. The initial euphoria experienced at the beginning, however, has subsided, with the result that most centers still practicing IORT are academic institutions. The reason for the reduction in IORT performed at community hospitals is partly related to the method of treatment--namely, transporting the patient from the OR to the radiation therapy department. The advent of mobile linear accelerators, which require little or no shielding and can therefore be used in most OR rooms, is likely to reiginite interest in this modality. There are currently six new centers in the United States that practice IORT with a mobile linear accelerator and more than that in Europe.     

Retroperitoneal soft tissue sarcomas: A pilot study of intraoperative radiation therapy

This pilot study was conducted to evaluate the feasibility and tolerance of a multimodal therapy of retroperitoneal soft tissue sarcoma (STS), including intraoperative radiation therapy (IORT). Nineteen patients (14 primarily treated patients and 5 treated for a recurrent tumor) were included. Surgery included a complete resection (14), a partial resection (2), and no resection (2). The median IORT dose was 17 Gy. Thirteen patients also received an external radiation therapy (ERT). Nine patients received chemotherapy. There was no postoperative mortality. Immediate postoperative complications occurred in four patients (21%). Delayed complications occurred in six patients, including one lethal iliac artery disruption. With a median follow-up of 17 months, the 2-year disease-free survival rate was 60%, and the 2-year actuarial local control rate was 76%. A multimodality approach of treatment, including IORT and ERT and eventually chemotherapy, appears feasible in patients with retroperitoneal STS. However, the treatment-related morbidity appeared relatively high in this study. © 1996 Wiley-Liss, Inc.     

The progression rate of late radiation effects in normal tissue and its impact on dose-response relationships

The progression of late skin telangiectasia after radiotherapy has been studied prospectively in patients for 1, 2 and 5 fractions per week and various dose levels. The degree of telangiectasia was scored on an arbitrary scale. Skin telangiectasia was found to be a continuously progressing endpoint both in the individual patient and in terms of the number of patients who achieved a certain degree of damage. The rate of progression was dose-dependent. Dose-response analysis were performed at 3, 5 and 9 years follow-up for various endpoints: telangiectasia score greater than or equal to 1, score greater than or equal to 2 and score greater than or equal to 3. Iso-effective doses (ED50S) for score greater than or equal to 1 at 3 years, score greater than or equal to 2 at 5 years and score greater than or equal to 3 at 9 years were very similar. In an iso-effect analysis it is therefore worthwhile and time-saving to include the minimal detectable damage in the endpoint (e.g. using score greater than or equal to 1), even if this mild damage is of no clinical significance, and the dose in the endpoint (e.g. using score greater than or equal to 1), even if this mild damage is of no clinical significance, and the dose response become somewhat less steep than for more severe damage. The fact that the progression rate is dose-dependent has impact on dose-response analysis. Dose-response analysis for score greater than or equal to 3 at various follow-up times showed a very flat curve at 3 years compared to 5 and 9 years. The steepness of the dose-response curves was similar at 5 and 9 years. A minimum follow-up of 5 years is therefore necessary for reliable estimation of the late complication rates in a comparison of two dosage schedules using this endpoint. The implication of the continuous progression of telangiectasia is that the dose-response curves are shifted to the left with follow-up. The ED50 is dramatically reduced between 3 and 5 years. The ED50 is also significantly reduced between 5 and 9 years' follow-up, in spite of no change in the steepness of the dose-response curve during this period. Consequently, the time of response is the most fundamental parameter in any iso-effect analysis with progressive endpoints and the late complication rates always have to be specified at a fixed time of follow-up.     

后程超分割治疗与鼻咽癌大容积原发肿瘤疗效关系的研究

目的:探讨常规分割放疗(CFRT)与后程超分割放疗(LHRT)对鼻咽癌大容积(≥60cm3)原发肿瘤的疗效关系。方法:无远处转移的182例初治鼻咽癌(T2～4N0～3Mo)。治疗前根据CT资料勾画鼻咽癌原发肿瘤,容积(≥60cm3),采用CFRT或LHRT照射,N3的病例均加用辅助化疗,分析比较两组疗效。结果:鼻咽癌大容积≥60cm3原发肿瘤无论T分期,采用LHRT较CFRT治疗,患者原发灶5年控制率对比有统计学意义。N0～2的患者无远处转移生存率对比,亦有统计学意义。结论:鼻咽癌大容积原发肿瘤无论T分期,(N0～2)后程采用超分割照射可提高鼻咽癌控制率及无瘤生存率,但N3的患者虽鼻咽癌控率可提高,但无远处转移生存率未见统计学意义的差异。     

HCC术中放疗的安全性研究

目的 采用队列研究方法探讨IOERT在Ⅰ期HCC治疗中的安全性。方法 2010—2012年间初次病理诊断为Ⅰ期HCC的16例患者接受了IOERT。采用队列研究方法筛选同期行单纯根治术的87例Ⅰ期HCC患者,根据肿瘤大小(>5 cm与≤5 cm)及切缘情况(近切缘与切缘阴性)进行1∶2配对,共32例为对照组。评价两组患者术中、术后不良事件,反映肝功能的生化、凝血象及血常规等指标变化,以及与IOERT相关的不良反应。独立样本t检验组间差异。结果 IOERT组与对照组相比,手术时间明显延长[(275.4±71.55) min和(184.7±64.74) min,P=0.000],术中不良事件发生率稍高(18.75%和6.25%,P=1.000),手术并发症发生率稍低(12.50%和28.12%,P=0.460),围手术期死亡率分别为0和6%(P=0.440)。反映肝功能的实验室指标两组均相近(P>0.05),术后均降至1级或恢复正常。中位术后住院时间、外科住院时间、切口愈合时间及切口愈合级别两组也相似(P>0.05)。IOERT组无放射性肝炎发生。结论 IOERT作为早期HCC术后的辅助治疗,对术后康复及肝功能等无影响,IORT剂量15~16 Gy是安全可行的。     

Significance of intraoperative radiation therapy and high cumulative radiation doses in retroperitoneal soft tissue sarcoma

IntroductionIn retroperitoneal soft tissue sarcoma (STS) local recurrence (LR) rates remain high despite more aggressive surgical approaches. Since wide resection margins cannot be achieved in all patients, application of intraoperative radiation therapy (IORT) has been frequently discussed. Still, the significance of IORT in multimodal treatment of retroperitoneal STS remains unclear.Material and methodsPatients undergoing resection of primary or recurrent retroperitoneal STS at the University of Heidelberg Department of General, Visceral and Transplantation Surgery were retrospectively analyzed. Univariate Kaplan-Meyer and multivariate Cox regression analyses were performed to identify predictors of LR-free survival and to investigate the impact of IORT and high cumulative radiation doses. Analyses with propensity-score matched subgroups for IORT and cumulative radiation dose were performed to control for selection bias. Subgroup analyses for patients with retroperitoneal liposarcoma were likewise performed.Results272 patients were identified. Recurrent tumors, histology of dedifferentiated liposarcoma or unclassified sarcoma and microscopically incomplete resection were associated with decreased LR-free survival. In liposarcoma, only recurrent and dedifferentiated tumors were confirmed as poor prognostic factors concerning LR. IORT and cumulative radiation doses exceeding 60 Gy did not influence LR rates (estimated 5-year LR-free survival: IORT: 39%, non-IORT: 46%; p = 0.79).ConclusionIn this retrospective evaluation, additional application of IORT does not significantly influence oncological outcome in retroperitoneal soft tissue sarcoma. Randomized trials are needed to clarify the benefit of IORT.     

Long-term results of intraoperative electron beam radiotherapy for primary and recurrent retroperitoneal soft tissue sarcoma

PURPOSE: This study assesses the long-term outcome of patients with retroperitoneal sarcoma treated by preoperative external beam radiotherapy, resection, and intraoperative electron beam radiation (IOERT). METHODS AND MATERIALS: From 1980 to 1996, 37 patients were treated with curative intent for primary or recurrent retroperitoneal soft tissue sarcoma. All patients underwent external beam radiotherapy with a median dose of 45 Gy. This was followed by laparotomy, resection, and IOERT, if feasible. Twenty patients received 10-20 Gy of IOERT with 9-15 MeV electrons. These patients were compared to a group of 17 patients receiving preoperative irradiation without IOERT. RESULTS: The 5-yr actuarial overall survival (OS), disease-free survival, local control (LC), and freedom from distant disease of all 37 patients was 50%, 38%, 59%, and 54%, respectively. After preoperative irradiation, 29 patients (78%) underwent gross total resection. For 16 patients undergoing gross total resection and IOERT, OS and LC were 74% and 83%, respectively. In contrast, these results were less satisfactory for 13 patients undergoing gross total resection without IOERT. For these patients, OS and LC were 30% and 61%, respectively. Four patients experienced treatment-related morbidity. CONCLUSIONS: In selected patients, IOERT results in excellent local control and disease-free survival with acceptable morbidity.     

The prevalence and severity of late effects in normal rat duodenum following intraoperative irradiation

In humans, a portion of the duodenum is often at risk for radiation-induced complications following intraoperative radiation therapy for pancreatic carcinoma. To determine experimentally the prevalence and severity of late effects in the normal mammalian duodenum, 190 rats received single doses of 0, 15, 20, 25, 30, or 40 Gy orthovoltage X rays to temporarily exteriorized 3 cm circumferential segments of duodenum. The animals were killed 2, 6, 8, or 10 months later. Actuarial survival, change in body weight, and a radiation injury score based on eight histopathologic alterations were used as endpoints. Epithelial atypia, intestinal wall fibrosis, serosal thickening, and vascular sclerosis were the dominant histopathologic alterations at all dose levels throughout the 10-month observation period. The prevalence and severity of histologic radiation injury showed sigmoidal dose-response relationships with the plateaus starting at 20 Gy. Doses of 20 Gy or greater also resulted in a substantial loss of body weight and a high level of early deaths (20-80 days). All endpoints indicate that intraoperative doses of 20 Gy or greater are associated with unacceptable risks of late and irreversible complications.     

A Clinical phase I/II trial to investigate preoperative dose-escalated intensity-modulated radiation therapy (IMRT) and intraoperative radiation therapy (IORT) in patients with retroperitoneal soft tissue sarcoma

ABSTRACT: BACKGROUND: Local control rates in patients with retroperitoneal soft tissue sarcoma (RSTS) remain disappointing even after gross total resection, mainly because wide margins are not achievable in the majority of patients. In contrast to extremity sarcoma, postoperative radiation therapy (RT) has shown limited efficacy due to its limitations in achievable dose and coverage. Although Intraoperative Radiation Therapy (IORT) has been introduced in some centers to overcome the dose limitations and resulted in increased outcome, local failure rates are still high even if considerable treatment related toxicity is accepted. As postoperative administration of RT has some general disadvantages, neoadjuvant approaches could offer benefits in terms of dose escalation, target coverage and reduction of toxicity, especially if highly conformal techniques like intensity-modulated radiation therapy (IMRT) are considered. METHODS: The trial is a prospective, one armed, single center phase I/II study investigating a combination of neoadjuvant dose-escalated IMRT (50-56 Gy) followed by surgery and IORT (10-12 Gy) in patients with at least marginally resectable RSTS. The primary objective is the local control rate after five years. Secondary endpoints are progression-free and overall survival, acute and late toxicity, surgical resectability and patterns of failure. The aim of accrual is 37 patients in the per-protocol population. DISCUSSION: The present study evaluates combined neoadjuvant dose-escalated IMRT followed by surgery and IORT concerning its value for improved local control without markedly increased toxicity. Trial Registration : NCT01566123.     

Cytosolic NAD(P)H:(quinone-acceptor)oxidoreductase in human normal and tumor tissue: effects of cigarette smoking and alcohol

NAD(P)H:(quinone-acceptor)oxidoreductase (QAO), previously known as DT-diaphorase, catalyzes the reduction of quinones to hydroquinones. Enhanced activity of the enzyme has been suggested to protect cells against the cellular toxicity and carcinogenicity of quinones, but may activate some cytotoxic anti-tumor quinones. Cytosolic levels of QAO, carbonyl reductase (CR) and total quinone reductase activity have been measured in normal and tumorous human tissues. QAO was the major component of the total cytosolic quinone reductase activity in all the tissues investigated. CR represented 10 to 28% of the total cytosolic quinone reductase activity in normal tissue. Normal tissue QAO was high in the stomach and kidney, and lower in the lung, liver, colon and breast. Primary tumor from lung, liver, colon and breast had elevated levels of QAO compared to normal tissue, while tumor from kidney and stomach had lower levels. CR was not significantly altered in tumor tissue, except in the case of lung and colon tumor which showed an increase compared to normal tissue. A major determinant of the variability of human lung tumor QAO was the cigarette-smoking history of the donor. Non-smokers and past smokers had high levels of tumor QAO compared to normal tissue. Smokers had levels of tumor QAO that were not significantly different from those of normal tissue QAO. Smokers had a small increase in normal lung QAO compared to non-smokers. Alcohol use was associated with an increase in lung tumor QAO but had no effect on QAO in normal lung. The function of QAO in tumors is not known but the elevated activity of QAO in some tumors and the apparent depressant effect of smoking could influence the response of these tumors to quinone drugs or toxic agents that are metabolized by QAO.     

Hematopoietic stem cell compartment: Acute and late effects of radiation therapy and chemotherapy

The bone marrow is an important dose-limiting cell renewal tissue for chemotherapy, wide-field irradiation, and autologous bone marrow transplantion. Over the past 5–10 years a great deal has been discovered about the hematopoietic stem cell compartment. Although the toxicity associated with prolonged myelosuppression continues to limit the wider use of chemotherapy and irradiation, ways are being discovered to circumvent this toxicity such as with the increasing use of cytokines. This review describes what is known of how chemotherapy and irradiation damage stem cells and the microenvironment, how cytokines protect hematopoietic cells from radiation damage and speed marrow recovery after chemotherapy or marrow transplantation, and how various types of blood marrow cells contribute to engraftment and long-term hematopoiesis after high doses of cytotoxic agents and/or total body irradiation.     

COMBINATION OF PRONE POSITION AND INTENSITY-MODULATED RADIATION THERAPY （IMRT） REDUCES SMALL BOWEL DOSES IN RADIATION THERAPY FOR GYNECOLOGIC MALIGNANCIES

Small bowel sequelae including obstruction, enteritis, and diarrhea, are among the most important acute and chronic toxicities in gynecologic carcinoma patients treated with pelvic radiotherapy[1, 2]. The total dose of radiation delivered to the pelvic organs by the whole pelvic external irradiation and intracavitary insertions is the most significant factor affecting the probability of these complications. The incidence of late bowel complications after pelvic irradiation isreported to be rel…     

Selective internal radiation therapy: 90Y (yttrium) labeled microspheres for liver malignancies (primary and metastatic)

Selective Internal Radiation Therapy is a relatively new technique that irradiates malignant liver lesions using microscopic beads. It provides micro-embolization coupled with high-dose interstitial radiotherapy. Besides colorectal cancers, this therapy has shown benefit in patients with a variety of other tumors including carcinoid tumors, lung, breast, sarcoma, colon, hepatocellular and ocular melanoma. Its clinical benefit can be as much as 85%, survival can be doubled and patients with extensive colorectal metastases not amenable to resection or ablation can be offered a 32% chance of surviving for 18 months. Ongoing and future studies will refine our understanding of optimizing patient eligibility, dosage, frequency as well as novel applications.