γ-体部立体定向放疗配合热疗及替吉奥治疗局部晚期胰腺癌的疗效分析

目的探讨γ-体部立体定向放疗（stereotactic body radiation therapy with γ-knife,γ-SBRT)配合热疗及替吉奥治疗局部晚期胰腺癌疗效。方法2012年6月—2013年4月,收治54例胰腺癌患者,30例行γ-SBRT配合热疗,24例行γ-SBRT配合热疗及替吉奥治疗。结果治疗后3个月总的有效率为79.6%(43/54)。γ-SBRT配合热疗的1年生存率为30.0%、中位生存期为9.4个月,γ-SBRT配合热疗及替吉奥的1年生存率为41-7%、中位生存期为12.2个月,差异有统计学意义（P＜0.05）。结论采用γ-SBRT配合热疗及替吉奥治疗局部中晚期胰腺癌是较有效的治疗方法。治疗过程安全,多数患者能耐受治疗。     

Testicular radiation dose after multimodal curative therapy for locally advanced rectal cancer

PURPOSE: The purpose of the current work was to prospectively measure the influence of testicular radiation dose on hormone levels, quality of life (QoL), and sexual functioning following multimodal therapy (neoadjuvant radiochemotherapy, surgery, and adjuvant chemotherapy) for rectal cancer. PATIENTS AND METHODS: From November 2007 to November 2009, 83?male patients were treated at the University of Goettingen with radiochemotherapy (RCT) for locally advanced rectal cancer [total dose 50.4?Gy, concomitant chemotherapy with two cycles of 5-fluorouracil (FU) or 5-FU and oxaliplatin]. Testicular radiation doses were analyzed and correlated with hormone levels [luteinizing hormone (LH), follicle stimulating hormone (FSH), total testosterone and free androgen index (FAI) serum levels], QoL, and sexual functioning, which were determined before and up to 1?year after RCT. RESULTS: Mean dose at the testes was 3.9?Gy (range 0.28-11.98?Gy). It was higher for tumors located 相似文献   

Stereotactic body radiation therapy planning with duodenal sparing using volumetric-modulated arc therapy vs intensity-modulated radiation therapy in locally advanced pancreatic cancer: A dosimetric analysis

Stereotactic body radiation therapy (SBRT) achieves excellent local control for locally advanced pancreatic cancer (LAPC), but may increase late duodenal toxicity. Volumetric-modulated arc therapy (VMAT) delivers intensity-modulated radiation therapy (IMRT) with a rotating gantry rather than multiple fixed beams. This study dosimetrically evaluates the feasibility of implementing duodenal constraints for SBRT using VMAT vs IMRT. Non–duodenal sparing (NS) and duodenal-sparing (DS) VMAT and IMRT plans delivering 25 Gy in 1 fraction were generated for 15 patients with LAPC. DS plans were constrained to duodenal D_max of<30 Gy at any point. VMAT used 1 360° coplanar arc with 4° spacing between control points, whereas IMRT used 9 coplanar beams with fixed gantry positions at 40° angles. Dosimetric parameters for target volumes and organs at risk were compared for DS planning vs NS planning and VMAT vs IMRT using paired-sample Wilcoxon signed rank tests. Both DS VMAT and DS IMRT achieved significantly reduced duodenal D_mean, D_max, D_1cc, D_4%, and V_20 Gy compared with NS plans (all p≤0.002). DS constraints compromised target coverage for IMRT as demonstrated by reduced V_95% (p = 0.01) and D_mean (p = 0.02), but not for VMAT. DS constraints resulted in increased dose to right kidney, spinal cord, stomach, and liver for VMAT. Direct comparison of DS VMAT and DS IMRT revealed that VMAT was superior in sparing the left kidney (p<0.001) and the spinal cord (p<0.001), whereas IMRT was superior in sparing the stomach (p = 0.05) and the liver (p = 0.003). DS VMAT required 21% fewer monitor units (p<0.001) and delivered treatment 2.4 minutes faster (p<0.001) than DS IMRT. Implementing DS constraints during SBRT planning for LAPC can significantly reduce duodenal point or volumetric dose parameters for both VMAT and IMRT. The primary consequence of implementing DS constraints for VMAT is increased dose to other organs at risk, whereas for IMRT it is compromised target coverage. These findings suggest clinical situations where each technique may be most useful if DS constraints are to be employed.     

Image-guidance for stereotactic body radiation therapy.

The term stereotactic body radiation therapy (SBRT) describes a recently introduced external beam radiation paradigm by which small lesions outside the brain are treated under stereotactic conditions, in a single or few fractions of high-dose radiation delivery. Similar to the treatment planning and delivery process for cranial radiosurgery, the emphasis is on sparing of adjacent normal tissues through the creation of steep dose gradients. Thus, advanced methods for assuring an accurate relationship between the target volume position and radiation beam geometry, immediately prior to radiation delivery, must be implemented. Such methods can employ imaging techniques such as planar (e.g., x-ray) or volumetric (e.g., computed tomography [CT]) approaches and are commonly summarized under the general term image-guided radiation therapy (IGRT). This review summarizes clinical experience with volumetric and ultrasound based image-guidance for SBRT. Additionally, challenges and potential limitations of pre-treatment image-guidance are presented and discussed.     

Risk-adapted robotic stereotactic body radiation therapy for inoperable early-stage non-small-cell lung cancer

Purpose

To evaluate efficacy and toxicity of stereotactic body radiation therapy (SBRT) with CyberKnife® (Accuray, Sunnyvale, CA, USA) in a selected cohort of primary, medically inoperable early-stage non-small cell lung cancer (NSCLC) patients.

Methods

From 2012 to 2016, 106 patients (median age 74 years, range 50–94 years) with primary NSCLC were treated with SBRT using CyberKnife®. Histologic confirmation was available in 87 patients (82%). For mediastinal staging, 92 patients (87%) underwent ¹⁸F-fluorodeoxyglucose positron-emission tomography (18-FDG-PET) and/or endobronchial ultrasound (EBUS)-guided lymph node biopsy or mediastinoscopy. Tumor stage (UICC8, 2017) was IA/B (T1a-c, 1–3?cm) in 86 patients (81%) and IIA (T2a/b, 3–5?cm) in 20?patients (19%). Depending on tumor localization, three different fractionation schedules were used: 3 fractions of 17Gy, 5 fractions of 11Gy, or 8 fractions of 7.5?Gy. Tracking was based on fiducial implants in 13 patients (12%) and on image guidance without markers in 88%.

Results

Median follow-up was 15 months (range 0.5–46 months). Acute side effects were mild (fatigue grade 1–2 in 20% and dyspnea grade 1–2 in 17%). Late effects were observed in 4 patients (4%): 3 patients developed pneumonitis requiring therapy (grade 2) and 1 patient suffered a rib fracture (grade 3). In total, 9/106 patients (8%) experienced a local recurrence, actuarial local control rates were 88% (95% confidence interval, CI, 80–96%) at 2 years and 77% (95%CI 56–98%) at 3 years. The median disease-free survival time was 27 months (95%CI 23–31 months). Overall survival was 77% (95%CI 65–85%) at 2 years and 56% (95%CI 39–73%) at 3 years.

Conclusion

CyberKnife® lung SBRT which allows for real-time tumor tracking and risk-adapted fractionation achieves satisfactory local control and low toxicity rates in inoperable early-stage primary lung cancer patients.

     

Evaluation of intraoperative radiation therapy for unresectable pancreatic cancer with FDG PET.

This investigation was undertaken to evaluate 18F-labeled fluorodeoxyglucose (FDG) PET in monitoring patients after intraoperative radiotherapy (IORT) for unresectable pancreatic cancer and to compare its usefulness with CT. METHODS: FDG PET was performed in 12 consecutive unresectable ductal adenocarcinoma patients before (n = 12) and after IORT (0.7-11.9 mo, n = 14). In the follow-up period, FDG PET results after IORT were divided into three groups: early (0-2.0 mo after IORT, n = 7), intermediate (2.1-4.0 mo, n = 5) and delayed period (4.1 mo or later, n = 2). FDG uptake at 60 min after injection of 185 MBq FDG under fasting conditions was analyzed with standardized uptake value (SUV). Three parameters, the highest SUV in the tumor, the area of tumor showing SUV of more than 2.0 and the average SUV in the tumor area were calculated. Ratios of each parameter after IORT to that before IORT were defined as residual uptake ratio (RUR)-1, -2 and -3, respectively. Tumor regression after IORT was evaluated with CT as tumor size ratio (TSR) every 2 mo. RESULTS: Results of RUR-1 and -3 were consistent with tumor size measured by CT. They decreased in 10 patients with partial response and increased in 2 patients with no change, although these 2 patients had abscesses. RUR-3 decreased consistently as 0.65+/-0.33 in 2 mo, 0.51+/-0.39 in 4 mo and 0.24 in 4 mo or later after IORT, respectively. RUR-1 decreased in early period, but demonstrated no change through the remaining periods. There were discrepancies between the results of RUR-2 and those of the other RURs. CT results revealed a slow decrease in tumor size, because TSR was 0.91 +/-0.10, 0.76+/-0.11 and 0.70+/-0.18 in 2, 4 and 6 mo after IORT, respectively. RUR-3 was smaller than TSR at 2 mo (P < 0.05) and 4 mo (P = 0.056). These results indicate that the measurement of the average SUV in the tumor area with FDG PET could evaluate the local response of pancreatic cancer after IORT earlier and more markedly than with CT. CONCLUSION: FDG PET was useful in monitoring patients after IORT, because the decrease of metabolism in pancreatic tumor could be detected earlier than the decrease in tumor size.     

A dosimetric evaluation of dose escalation for the radical treatment of locally advanced vulvar cancer by intensity-modulated radiation therapy

The purpose of this planning study was to determine whether intensity-modulated radiation therapy (IMRT) reduces the radiation dose to organs at risk (OAR) when compared with 3D conventional radiation therapy (3D-CRT) in patients with vulvar cancer treated by irradiation. This study also investigated the use of sequential IMRT boost (seq-IMRT) and simultaneous integrated boost (SIB-IMRT) for dose escalation in the treatment of locally advanced vulvar cancer. Five vulvar cancer patients treated in the postoperative setting and 5 patients treated with definitive intent (def-group) were evaluated. For the postoperative group, 3D-CRT and IMRT plans to a total dose (TD) of 45 Gy were generated. For the def-group, 4 plans were generated: a 3D-CRT and an IMRT plan to a TD of 56.4 Gy, a SIB-IMRT plan to a TD of 56 Gy, and a SIB-IMRT with dose escalation (SIB-IMRT-esc): TD of 67.2 Gy. Mean dose and dose-volume histograms were compared using Student's t-test. IMRT significantly (all p < 0.05) reduced the D_mean, V30, and V40 for all OAR in the adjuvant setting. The V45 was also significantly reduced for all OAR except the bladder. For patients treated in the def-group, all IMRT techniques significantly reduced the D_mean, V40, and V45 for all OAR. The mean femur doses with SIB-IMRT and SIB-IMRT-esc were 47% and 49% lower compared with 3D-CRT. SIB-IMRT-esc reduced the doses to the OAR compared with seq-3D-CRT but increased the D_max. for the small bowel, rectum, and bladder. IMRT reduces the dose to the OAR compared with 3D-CRT in patients with vulvar cancer receiving irradiation to a volume covering the vulvar region and nodal areas without compromising the dosimetric coverage of the target volume. IMRT for vulvar cancer is feasible and an attractive option for dose escalation studies.     

立体定向放射治疗在结直肠癌肝转移中的临床应用

目的 评价立体定向放射治疗（SBRT）在结直肠癌肝转移（CLM）中的治疗效果,为合理选择治疗手段提供依据。方法 解放军306医院收治的28例患者,包括男17例,女11例,中位年龄63.8岁（31~86岁）,共计54个病灶,行立体定向放射治疗。平静呼吸状态下的CT增强扫描影像分别进行大体肿瘤体积（GTV）、临床靶区体积（CTV）和计划靶区体积（PTV）的勾画,CTV为GTV外放5 mm,GTV为CTV外放5~10 mm。以50%~60%等剂量曲线作为处方剂量曲线,单次3~6 Gy,总剂量39~45 Gy,等效生物剂量50.7~65.3 Gy。治疗后3个月开始复查,以增强CT或MR显示的病灶体积的变化做为评价疗效的依据。根据RTOG毒性诊断标准对不良反应进行诊断和分级,比较局控率和生存率。结果 所有患者均顺利完成治疗,中位随访时间为15.1个月（3~30个月）,随访终点有7例患者存活。局控率为79.2%,1年和2年的总生存率分别为82.7%和48.6%。病灶体积与局控率关系密切,当体积小于14 cm³时,肿瘤局控率明显高于病灶体积大于65 cm³时（χ² = 4.17,P<0.05）。病灶体积大于180 cm³时,肿瘤局控率为零。不良反应包括治疗后乏力（60.7%）,1、2级消化道反应（28.6%）,一过性1、2级骨髓抑制（46.4%）,一过性转氨酶增高（17.8%）。全组未发生3级以上及晚期不良反应。结论 立体定向放射治疗可做为选择性病例尤其是不能手术的结直肠癌肝转移患者的首选局部治疗手段。     

Frame-based immobilization and targeting for stereotactic body radiation therapy.

Frame-based stereotactic body radiation therapy (SBRT), such as that conducted with Elekta's Stereotactic Body Frame, can provide an extra measure of precision in the delivery of radiation to extracranial targets, and facilitates secure patient immobilization. In this paper, we review the steps involved in optimal use of an extra-cranial immobilization device for SBRT treatments. Our approach to using frame-based SBRT consists of 4 steps: patient immobilization, tumor and organ motion control, treatment/planning correlation, and daily targeting with pretreatment quality assurance. Patient immobilization was achieved with the Vac-Loc bag, which uses styrofoam beads to conform to the patient's shape comfortably within the body frame. Organ and motion control was assessed under fluoroscopy and controlled via a frame-mounted abdominal pressure plate. The compression screw was tightened until the diaphragmatic excursion range was < 1 cm. Treatment planning was performed using the Philips Pinnacle 6.2b system. In this treatment process, a 20 to 30 noncoplanar beam arrangement was initially selected and an inverse beam weight optimization algorithm was applied. Those beams with low beam weights were removed, leaving a manageable number of beams for treatment delivery. After planning, daily targeting using computed tomography (CT) to verify x-, y-, and z-coordinates of the treatment isocenter were used as a measure of quality assurance. We found our daily setup variation typically averaged < 5 mm in all directions, which is comparable to other published studies on Stereotactic Body Frame. Treatment time ranged from 30 to 45 minutes. Results demonstrate that patients have experienced high rates of local control with acceptable rates of severe side effects - by virtue of the tightly constrained treatment fields. The body frame facilitated comfortable patient positioning and quality assurance checks of the tumor, in relation to another set of independent set of coordinates defined by the body frame fiducials. The ability to impose abdominal compression proved to be a simple way to reduce target and tissue motion. SBRT with Stereotactic Body Frame enables comfortable patient immobilization and facilitates repeated registering and re-registering of the patient to the frame. With the body frame, large-dose-per fraction treatment is possible for localized tumor deposits with the aim of attaining a more therapeutic result.     

Radiofrequency ablation as salvage therapy for unresectable locally recurrent rectal cancer

Despite total mesorectal resection, often with accompanying chemoradiation therapy, local recurrence continues to cause significant morbidity and mortality in cases of rectal cancer. Recurrent rectal cancers are often inoperable as a result of pelvic sidewall and sacral invasion. The authors describe the use of radiofrequency (RF) ablation to manage an unresectable multiply recurrent rectal cancer in which complete ablation with durable long-term control was achieved despite the large size of the tumor. RF ablation is a viable option for patients who are poor surgical candidates or whose disease is not amenable to conventional surgical approaches.     

Magnetic resonance image-guided adaptive stereotactic body radiotherapy for prostate cancer: preliminary results of outcome and toxicity

Objective:Using moderate or ultra-hypofractionation, which is also known as stereotactic body radiotherapy (SBRT) for treatment of localized prostate cancer patients has been increased. We present our preliminary results on the clinical utilization of MRI-guided adaptive radiotherapy (MRgRT) for prostate cancer patients with the workflow, dosimetric parameters, toxicities and prostate-specific antigen (PSA) response.Methods:50 prostate cancer patients treated with ultra-hypofractionation were included in the study. Treatment was performed with intensity-modulated radiation therapy (step and shoot) technique and daily plan adaptation using MRgRT. The SBRT consisted of 36.25 Gy in 5 fractions with a 7.25 Gy fraction size. The time for workflow steps was documented. Patients were followed for the acute and late toxicities and PSA response.Results:The median follow-up for our cohort was 10 months (range between 3 and 29 months). The median age was 73.5 years (range between 50 and 84 years). MRgRT was well tolerated by all patients. Acute genitourinary (GU) toxicity rate of Grade 1 and Grade 2 was 28 and 36%, respectively. Only 6% of patients had acute Grade 1 gastrointestinal (GI) toxicity and there was no Grade ≥ 2 GI toxicity. To date, late Grade 1 GU toxicity was experienced by 24% of patients, 2% of patients experienced Grade 2 GU toxicity and 6% of patients reported Grade 2 GI toxicity. Due to the short follow-up, PSA nadir has not been reached yet in our cohort.Conclusion:In conclusion, MRgRT represents a new method for delivering SBRT with markerless soft tissue visualization, online adaptive planning and real-time tracking. Our study suggests that ultra-hypofractionation has an acceptable acute and very low late toxicity profile.Advances in knowledge:MRgRT represents a new markerless method for delivering SBRT for localized prostate cancer providing online adaptive planning and real-time tracking and acute and late toxicity profile is acceptable.     

Radiation pneumonitis after stereotactic radiation therapy for lung cancer

Stereotactic body radiation therapy (SBRT) has a local control rate of 95% at 2 years for non-small cell lung cancer (NSCLC) and should improve the prognosis of inoperable patients, elderly patients, and patients with significant comorbidities who have early-stage NSCLC. The safety of SBRT is being confirmed in international, multi-institutional Phase II trials for peripheral lung cancer in both inoperable and operable patients, but reports so far have found that SBRT is a safe and effective treatment for early-stage NSCLC and early metastatic lung cancer. Radiation pneumonitis (RP) is one of the most common toxicities of SBRT. Although most post-treatment RP is Grade 1 or 2 and either asymptomatic or manageable, a few cases are severe, symptomatic, and there is a risk for mortality. The reported rates of symptomatic RP after SBRT range from 9% to 28%. Being able to predict the risk of RP after SBRT is extremely useful in treatment planning. A dose-effect relationship has been demonstrated, but suggested dose-volume factors like mean lung dose, lung V20, and/or lung V2.5 differed among the reports. We found that patients who present with an interstitial pneumonitis shadow on computed tomography scan and high levels of serum Krebs von den Lungen-6 and surfactant protein D have a high rate of severe radiation pneumonitis after SBRT. At our institution, lung cancer patients with these risk factors have not received SBRT since 2006, and our rate of severe RP after SBRT has decreased significantly since then.     

Identifying disparities in brachytherapy delivery for locally advanced cervical cancer

IntroductionThe standard of care for locally advanced cervical cancer is concurrent chemotherapy and external beam radiation therapy (EBRT) followed by a brachytherapy boost. Some studies show a decreased usage of brachytherapy in cervical cancer patients despite the standard of care and known survival advantage. This study aims to characterize the utilization of brachytherapy in Oregon and identify where disparities in treatment may exist.MethodsThe Oregon State Cancer Registry database was used to identify patients diagnosed with FIGO Stage IB2-IVB cervical cancer between 2007 and 2016. Patients who received initial EBRT were categorized by whether they received brachytherapy boost or not. Age at diagnosis, county of patient residence, rural-urban status of the county, race/ethnicity, and insurance payer were studied using multivariable logistic regression to identify possible underserved populations. Survival data was compared using a Cox proportional hazard survival model.Results401 patients who received primary EBRT for FIGO stage IB2-IVB cervical cancer were identified in the 10-year span. Breakdown by stage is: 16% stage IB2, 23.9% stage II, 37.4% stage III, and 22.7% stage IV. Of those, 154 (38.4%) received brachytherapy boost treatment, 75 (18.7%) received a different boost modality, and 42.9% received no boost. Stage IV (p = 0.001) and uninsured patients (p = 0.04) were significantly less likely to receive brachytherapy. Older age was also associated with decreased brachytherapy usage, as each additional year of life decreased brachytherapy receipt by 1.8% (p = 0.04). Native American and Pacific Islander patients were the only group significantly more likely to receive brachytherapy (p=0.003). There was no significant difference in the rate of brachytherapy boost identified based on urban/rural status of the county (p = 0.63 to 0.69), other racial/ethnic categories (p = 0.66 to 0.80), or among the other stages (p=0.45 to 0.63). In Cox proportional hazard survival analysis, patients that received brachytherapy showed a 42% reduction in risk of cancer specific mortality, though this did not reach the predetermined level of statistical significance (p = 0.057).ConclusionsThe brachytherapy boost rate among locally advanced cervical cancer patients was 38.4%. The data also indicated a likely reduction in cancer specific mortality in patients receiving brachytherapy. Older patients, stage IV patients, and uninsured patients were less likely to receive brachytherapy. Given the low overall brachytherapy usage, these data indicate access and delivery of brachytherapy care needs to be improved across the state. The increased brachytherapy use in the American Indian and Pacific Islander patient population should be further studied to identify facilitators to treatment completion and potentially extrapolate to other groups.     

立体定向放疗应用于肺寡转移灶的疗效与预后

目的 分析立体定向放射治疗（stereotactic body radiation therapy,SBRT）应用于肺寡转移灶的疗效与预后。方法 回顾性分析2012-2018年本院SBRT肺寡转移患者104例临床资料,2015年12月前的患者采用调强放疗（intensity modulated radiation therapy,IMRT）技术行立体定向放射治疗,2015年12月后的患者采用螺旋断层放疗（helical tomotherapy,HT）技术行立体定向放射治疗,用Kaplan-Meier方法计算局部控制（local control,LC）、无进展生存期（progression-free survival,PFS）及总生存（overall survival,OS）,Cox回归模型进行单因素与多因素分析,NCICTCAE V4.0标准评价放疗的不良反应。结果 1、2、3年的LC分别为86.6%、75.9%、72.3%,PFS分别为40.9%、28.4%、22.1%,OS分别为75.9%、53.2%、43.53%,中位OS为26.6个月。多因素分析显示原发肿瘤的病理类型、肺部结节的体积及SBRT治疗前癌胚抗原水平（carcino-embryonic antigen,CEA）为LC的独立预后因素（χ²=28.66,P<0.05）,SBRT后的进展方式为OS的独立预后因素（χ²=40.01,P<0.05）,HT-SBRT与IMRT-SBRT的LC及OS差异无统计学意义（P>0.05）;治疗的主要不良反应为放射性肺炎（25例,24.04%）,2级及以上放射性肺炎的发生率不超过7%。结论 SBRT应用于肺寡转移灶的治疗局部控制率高,不良反应可接受,HT-SBRT与IMRT-SBRT的疗效相当,不良反应差异无统计学意义,可广泛应用于临床。     

CivaSheet intraoperative radiation therapy for pancreatic cancer

The treatment of borderline resectable (BR) pancreatic cancer is challenging and requires a multidisciplinary approach with chemotherapy, radiation and surgical resection. Despite using chemotherapy and radiotherapy in the neoadjuvant setting, achievement of negative surgical margins remains technically challenging. Positive margins are associated with increased local recurrences and worse overall survival and there are no standard options for treatment.The CivaSheet is an FDA-cleared implantable sheet with a matrix of unidirectional planar low-dose-rate (LDR) Palladium-103 (Pd-103) sources. The sources are shielded on one side with gold to spare radio-sensitive structures such as the bowel. The sheet can easily be customized and implanted at the time of surgery when there is concern for close or positive margins.The CivaSheet provides an interesting solution to target the region of close/positive margins after pancreatectomy. Here we discuss the physical properties, the dosimetry, clinical workflow and early patient outcomes with the CivaSheet in pancreatic cancer.