MR-guided simultaneous integrated boost in preoperative radiotherapy of locally advanced rectal cancer following neoadjuvant chemotherapy

Purpose

To evaluate a simultaneous integrated boost (SIB) strategy in preoperative radiotherapy of rectal cancer patients following neoadjuvant chemotherapy using pre- and post-chemotherapy tumor volumes assessed by MRI.

Materials and methods

Ten patients with locally advanced rectal cancer, receiving chemotherapy prior to radiotherapy, were included in this study. Pre- and post-chemotherapy MR tumor images were co-registered with CT images for IMRT planning. Three planning target volumes were defined: PTV_risk, PTV_{pre_chemo} and PTV_{post_chemo}. For SIB, prescribed mean doses to the PTVs were 46, 50 and 58 Gy, respectively, given in 25 fractions. Organs at risk (OARs) were bladder and intestine. The novel three-volume SIB strategy was compared to a conventional two-volume SIB plan, in which PTV_{post_chemo} was ignored, using dose-volume histograms (DVHs) and the generalized equivalent uniform dose (gEUD).

Results

All patients showed tumor shrinkage following chemotherapy. For the novel SIB, population-based mean doses given to PTV_risk, PTV_{pre_chemo} and PTV_{post_chemo} were 46.8 ± 0.3, 50.6 ± 0.4 and 58.1 ± 0.4 Gy, respectively. DVHs and gEUDs for PTV_risk, PTV_{pre_chemo}, bladder and intestine revealed minimal differences between the two SIB strategies.

Conclusions

Tumor volume reduction for rectal cancer patients following neoadjuvant chemotherapy allows for increased tumor dose using a SIB strategy without increased OAR toxicity.     

Phase II study of preoperative helical tomotherapy for rectal cancer

PURPOSE: To explore the efficacy and toxicity profile of helical tomotherapy in the preoperative treatment of patients with rectal cancer. PATIENTS AND METHODS: Twenty-four patients with T3/T4 rectal cancer were included in this nonrandomized noncontrolled study. A dose of 46 Gy in daily fractions of 2 Gy was delivered to the presacral space and perineum if an abdominoperineal resection was deemed necessary. This dose was increased by a simultaneous integrated boost to 55.2 Gy when the circumferential resection margin was less than 2 mm on magnetic resonance imaging. Acute toxicity was evaluated weekly. Metabolic response was determined in the fifth week after the end of radiotherapy by means of fluorodeoxyglucose-positron emission tomography scan. A metabolic response was defined as a decrease in maximal standardized uptake value of more than 36%. RESULTS: The mean volume of small bowel receiving more than 15 Gy and mean bladder dose were 227 ml and 20.8 Gy in the no-boost group and 141 ml and 21.5 Gy in the boost group. Only 1 patient developed Grade 3 enteritis. No other Grade 3 or 4 toxicities were observed. Two patients developed an anastomotic leak within 30 days after surgery. The metabolic response rate was 45% in the no-boost group compared with 77% in the boost group. All except 1 patient underwent an R0 resection. CONCLUSIONS: Helical tomotherapy may decrease gastrointestinal toxicity in the preoperative radiotherapy of patients with rectal cancer. A simultaneous integrated radiation boost seems to result in a high metabolic response rate without excessive toxicity.     

Preoperative concomitant boost intensity-modulated radiotherapy with oral capecitabine in locally advanced mid-low rectal cancer: A phase II trial

Purpose

We aimed to assess the safety and efficacy of preoperative intensity-modulated radiotherapy (IMRT) with oral capecitabine in patients with locally advanced mid-low rectal cancer using a concomitant boost technique.

Materials and methods

Patients with resectable locally advanced mid-low rectal cancer (node-negative ?T3 or any node-positive tumor) were eligible. The eligible patients received IMRT to 2 dose levels simultaneously (50.6 and 41.8 Gy in 22 fractions) with concurrent capecitabine 825 mg/m² twice daily 5 days/week. The primary end point included toxicity, postoperative complication, and pathological complete response rate (ypCR). The secondary endpoints included local recurrence rate, progression-free survival (PFS), and overall survival (OS).

Results

Sixty-three eligible patients were enrolled; five patients did not undergo surgery. Of the 58 patients evaluable for pathologic response, the ypCR rate was 31.0% (95% CI 19.1-42.9). Grade 3 toxicities included diarrhea (9.5%), radiation dermatitis (3.2%), and neutropenia (1.6%). There was no Grade 4 toxicity reported. Four (6.9%) patients developed postoperative complications. Two-year local recurrence rate, PFS, and OS were 5.7%, 90.5%, and 96.0%, respectively.

Conclusions

The design of preoperative concurrent boost IMRT with oral capecitabine could achieve high rate of ypCR with an acceptable toxicity profile.     

适形调强放疗同期整合瘤床推量治疗肺癌脑转移瘤的可行性研究

背景与目的：肺癌脑转移的发生率呈上升趋势,适形调强放射治疗(intensity-modulated radiotherapy,IMRT)+瘤床同期整合推量(simultaneous integrated boost,SIB)技术对于脑转移患者是一种新的治疗选择。本研究旨在探讨全脑IMRT+瘤床SIB治疗合并1~4个肺癌脑转移灶患者的近期临床疗效及治疗相关不良反应,明确该方案的可行性。方法：前瞻性收集2014年6月-2015年6月在江门市中心医院确诊为肺癌脑转移(转移病灶数1~4个)的32例患者,所有患者均行全脑5野IMRT(40 Gy/20 f)+瘤床SIB(50 Gy/20 f),分别评价其靶区剂量分布、放疗总有效率、肿瘤局部控制率、1年生存率、各种急性及晚期不良反应。结果：所有患者均完成放疗。全组2级呕吐、恶心和癫痫发生率分别为9.4%、15.6%和12.5%,2例出现2级认知功能障碍,4例出现2级记忆力损伤,2例出现3级记忆力损伤,无4级急性及晚期不良反应。放疗总有效率为71.9%,肿瘤局部控制率为96.9%,1年生存率为44%。结论：全脑5野IMRT(40 Gy/20 f)+瘤床SIB(共10 Gy,即总量50 Gy/20 f) 治疗1~4个肺癌脑转移灶是可行的。     

High-dose simultaneously integrated breast boost using intensity-modulated radiotherapy and inverse optimization

PURPOSE: Recently a Phase III randomized trial has started comparing a boost of 16 Gy as part of whole-breast irradiation to a high boost of 26 Gy in young women. Our main aim was to develop an efficient simultaneously integrated boost (SIB) technique for the high-dose arm of the trial. METHODS AND MATERIALS: Treatment planning was performed for 5 left-sided and 5 right-sided tumors. A tangential field intensity-modulated radiotherapy technique added to a sequentially planned 3-field boost (SEQ) was compared with a simultaneously planned technique (SIB) using inverse optimization. Normalized total dose (NTD)-corrected dose volume histogram parameters were calculated and compared. RESULTS: The intended NTD was produced by 31 fractions of 1.66 Gy to the whole breast and 2.38 Gy to the boost volume. The average volume of the PTV-breast and PTV-boost receiving more than 95% of the prescribed dose was 97% or more for both techniques. Also, the mean lung dose and mean heart dose did not differ much between the techniques, with on average 3.5 Gy and 2.6 Gy for the SEQ and 3.8 Gy and 2.6 Gy for the SIB, respectively. However, the SIB resulted in a significantly more conformal irradiation of the PTV-boost. The volume of the PTV-breast, excluding the PTV-boost, receiving a dose higher than 95% of the boost dose could be reduced considerably using the SIB as compared with the SEQ from 129 cc (range, 48-262 cc) to 58 cc (range, 30-102 cc). CONCLUSIONS: A high-dose simultaneously integrated breast boost technique has been developed. The unwanted excessive dose to the breast was significantly reduced.     

Treatment outcomes and dose-volume histogram analysis of simultaneous integrated boost method for malignant gliomas using intensity-modulated radiotherapy

Background The aim of this article is to report the treatment outcomes, toxicities, and dosimetric feasibility of our simultaneous-boost intensity-modulated radiotherapy (SIB-IMRT) protocol. Methods Thirteen patients with malignant gliomas treated between December 2000 and September 2004 were enrolled in this study. Two planning target volumes (PTVs) were defined in the present study. Our IMRT regimen delivered 70 Gy/28 fractions (fr)/daily; 2.5 Gy to the gross tumor volume (GTV) with a 0.5-cm margin, defined as the PTV-G, and 56 Gy/28 fr/daily, with 2.0 Gy to the surrounding edema, defined as the planning target volume annulus (PTV-a). Eleven of the 13 patients received one or two courses of nimustine hydrochloride (ACNU) (100 mg/m²) and vincristine (1.2 mg/body) and interferon-β (3 × 10⁶ units) three times weekly during the period of radiotherapy. Adjuvant chemotherapy, ACNU (100 mg/m²) and vincristine (1.2 mg/body), was repeated every 6 weeks and interferon-β was repeated every 2 weeks. The treatment outcomes, toxicity, and dosimetric feasibility were assessed. Results All the patients experienced tumor recurrence. The median progression-free survival times for patients with grade III tumors and glioblastome were 7.5 and 8.0 months, respectively. The 1-year and 2-year overall survival rates for all the patients were 77% and 31%, respectively. Four patients experienced acute grade 1/2 toxicities during the treatment. No late toxicity related to radiotherapy has been seen. Analyses with dose-volume histograms confirmed excellent conformity of dose distributions in the two target volumes, PTV-G and PTV-a, with the sparing of organs at risk. Conclusion Our IMRT regimen did not prevent tumor progression. However, the ability of IMRT to deliver highly conformative doses to two contiguous targets, GTV and the surrounding edema, justifies its application to malignant gliomas.     

Dosimetric feasibility on hypofractionated intensity-modulated radiotherapy and simultaneous integrated boost for locally advanced unresectable pancreatic cancer with helical tomotherapy

BackgroundThis dosimetric study on locally advanced pancreatic cancer (LAPC) and the surrounding gastrointestinal organs at risk (OARs) aimed at exploring the potential of further improving the internal dose and reducing the fractionation number by concurrent hypofractionated simultaneous integrated boost (SIB) radiotherapy using helical tomotherapy (HT).MethodsWe collected computed tomography positioning images from a LAPC study of 17 consecutive patients. Gross tumor volume (GTV)1, GTV2, and GTV3 were defined as the GTV minus a margin of 3, 6, and 9 mm from the external part in all directions, respectively. Under the same physical parameters and limited dose on normal organs, each case had 4 sets of SIB radiotherapy plans. Upon dose escalation, we statistically analyzed the difference of dosimetric parameters received by the OARs between group A [planning target volume (PTV)/GTV=50 Gy/70 Gy] and the other groups. According to the equivalent bioradiotherapy formula, we calculated the hypofractionated standard dose by converting the average tolerated dose of each OAR with the corresponding number of fractions. Then, we compared the dose and volume parameters of the gastrointestinal tract from the less-than-20-fraction modes with the corresponding gastrointestinal hypofractionated standard dose.ResultsFor dose escalation, although there were a few differences in the parameters of the OAR between group A and group D, all OAR doses of group D (PTV/GTV/GTV1/GTV2/GTV3=50 Gy/70 Gy/80 Gy/90 Gy/100 Gy) were within the limited dose range. In the hypofractionated mode, there was a statistically significant difference between the gastrointestinal dose-volume parameters and the dose-limiting reference standard when the fraction number was less than 14 or 15 for group A or D, respectively.ConclusionsThe dose of the internal target can be increased to 100 Gy with 15 fractions in the hypofractionated SIB radiotherapy for LAPC with HT. The corresponding tolerance dose of OARs may also be acceptable.     

Phase I-II trial of concurrent capecitabine and oxaliplatin with preoperative intensity-modulated radiotherapy in patients with locally advanced rectal cancer

PURPOSE: To identify the maximal tolerated dose level of preoperative intensity-modulated radiotherapy combined with capecitabine and oxaliplatin and to evaluate the efficacy. PATIENTS AND METHODS: Patients with rectal T3-T4 and/or N0-N+ rectal cancer received capecitabine 825 mg/m(2) twice daily Monday through Friday and oxaliplatin 60 mg/m(2) intravenously on Days 1, 8, and 15, concurrently with intensity-modulated radiotherapy. The radiation dose was increased in 5.0-Gy steps in cohorts of 3 patients starting from 37.5 Gy in 15 fractions (dose level [DL] 1). DL2 and DL3 were designed to reach 42.5 Gy in 17 fractions and 47.5 Gy in 19 fractions, respectively. RESULTS: No dose-limiting toxicity was observed at DL1 or DL2. Of the 3 patients treated at DL3, 1 presented with Grade 3 diarrhea, which was considered a dose-limiting toxicity, and 3 additional patients were added. Of the 6 patients treated at DL3, no new dose-limiting toxicities were observed, and DL3 was identified as the recommended dose in this study. Eight additional patients were treated at 47.5 Gy. Grade 2 proctitis was the most frequent adverse event (40%); Grade 3 diarrhea occurred in 2 patients (10%). All patients underwent surgery, and 17 patients (85%) underwent R0 resection. Four patients (20%) presented with a histologic response of Grade 4, 11 (55%) with Grade 3+, 2 (15%) with Grade 3, and 2 patients (10%) with Grade 2. CONCLUSION: The maximal tolerated dose in this study was 47.5 Gy. The high rates of pathologic response of Grade 3+ and 4 must be confirmed through the accrual of new patients in the Phase II study.     

Phase I trial of preoperative hypofractionated intensity-modulated radiotherapy with incorporated boost and oral capecitabine in locally advanced rectal cancer

PURPOSE: To determine the safety and efficacy of preoperative hypofractionated radiotherapy using intensity-modulated radiotherapy (IMRT) and an incorporated boost with concurrent capecitabine in patients with locally advanced rectal cancer. METHODS AND MATERIALS: The eligibility criteria included adenocarcinoma of the rectum, T3-T4 and/or N1-N2 disease, performance status 0 or 1, and age > or =18 years. Photon IMRT and an incorporated boost were used to treat the whole pelvis to 45 Gy and the gross tumor volume plus 2 cm to 55 Gy in 25 treatments within 5 weeks. The study was designed to escalate the dose to the gross tumor volume in 5-Gy increments in 3-patient cohorts. Capecitabine was given orally 825 mg/m(2) twice daily for 7 days each week during RT. The primary endpoint was the maximal tolerated radiation dose, and the secondary endpoints were the pathologic response and quality of life. RESULTS: Eight patients completed RT at the initial dose level of 55 Gy. The study was discontinued because of toxicity-six Grade 3 toxicities occurred in 3 (38%) of 8 patients. All patients went on to definitive surgical resection, and no patient had a pathologically complete response. CONCLUSION: This regimen, using hypofractionated RT with an incorporated boost, had unacceptable toxicity despite using standard doses of capecitabine and IMRT. Additional research is needed to determine whether IMRT is able to reduce the side effects during and after pelvic RT with conventional dose fractionation.     

Randomized controlled study comparing simultaneous modulated accelerated radiotherapy versus simultaneous integrated boost intensity modulated radiotherapy in the treatment of locally advanced head and neck cancer

Objectives

Comparison of two fractionation schedules of intensity modulated radiotherapy (IMRT) for locally advanced head and neck cancer – simultaneous integrated boost (SIB-IMRT) and simultaneous modulated accelerated radiotherapy (SMART) boost in terms of toxicity and survival end-point measures.

Dose-escalation using intensity-modulated radiotherapy for prostate cancer - Evaluation of the dose distribution with and without F-choline PET-CT detected simultaneous integrated boost

Background and purpose

The aim of the study was to evaluate the impact of a dose escalation to an ¹⁸F-choline PET-CT defined simultaneous integrated boost (IB) on the dose distribution and changes of the equivalent uniform dose (EUD).

Materials and methods

PET-CT was performed in 12 consecutive patients for treatment planning. An intraprostatic lesion was defined by a tumour-to-background uptake value ratio >2 (GTV_PET). Dose escalation was focused only on the intraprostatic lesion. Two comparisons were evaluated: whole prostate irradiation to 76 Gy ± boost to 80 Gy (C1) and whole prostate irradiation to 66.6 Gy ± boost to 83.25 Gy (C2).

Results

PTV/GTV_PET + margins were covered by a mean EUD of 75.9/76.1 Gy vs. 77.1/80.1 Gy (C1) and 66.5/66.2 Gy vs. 71.1/82.9 Gy (C2) (p < 0.01, respectively). Concerning the organs at risk, EUD increased slightly with an additional boost (mean EUD for bladder: C1 53.2 Gy vs. 53.8 Gy; C2 43.0 Gy vs. 45.1 Gy; for rectum: C1 52.0 Gy vs. 52.6 Gy; C2 43.0 Gy vs. 45.4 Gy; p < 0.01, respectively). The distance to the organs at risk had a significant impact on the respective maximum doses in the treatment plans with IB.

Conclusions

Treatment planning with IB allows an individually adapted dose escalation. The therapeutic ratio can be improved by a considerable dose escalation to the macroscopic tumour, but only minor EUD changes to the bladder and rectum.     

局部晚期直肠癌术前VMAT同期加量剂量学研究

目的 探讨开展直肠癌术前VMAT同期加量(SIB-VMAT58.75 Gy)剂量学可行性,为临床应用提供依据。方法 对9例Ⅱ-Ⅲ期直肠癌术前放化疗患者分别行SIB-VMAT58.75 Gy和非同期加量VMAT (VMAT50.00 Gy),SIB-VMAT58.75 Gy剂量分割模式为局部直肠病变及阳性淋巴结给予58.25 Gy分25次(2.35 Gy/次),盆腔淋巴引流区给予50 Gy分25次(2.0 Gy/次);VMAT50.00 Gy剂量分割模式为盆腔淋巴引流区50 Gy分25次(2.0 Gy/次)。利用DVH评价靶区CI、HI和OAR受量。配对t检验或配对非参数秩和检验。结果 两种计划均能满足靶区处方剂量要求;PTV两组CI相近(1.0±0.0、1.0±0.0,P>0.05);HISIB-VMAT58.75 Gy组差于HIVMAT50.00 Gy组(0.2±0.2、0.1±0.0,P<0.05)。SIB-VMAT58.75 Gy较VMAT50.00 Gy小肠D2 cm³稍增加(P=0.038),小肠、膀胱、股骨头、骨盆的V10-V50两种计划相近(P均>0.05)。结论 SIB-VMAT58.75 Gy计划可以满足靶区处方剂量及OAR剂量限制要求,在剂量学上安全可行,具体疗效及不良反应有待于临床研究进一步验证。     

同期整合加量调强放疗在食管癌中的应用进展

近年非常规分割放疗在多个系统肿瘤的治疗中日益体现出优势。同期整合加量调强放疗(SIB-IMRT)可以在一次照射过程中将不同的分割剂量传递至不同区域,实现在不增加正常组织受量前提下给予高危区域(GTV)局部追加剂量照射,其剂量学优势已得到学界广泛认可。目前,在食管癌领域SIB-IMRT的局控、生存优势、适应证人群、单次分割整合加量的上限界点仍然不明确,特就该技术在食管癌中的应用予以综述。     

颈及上胸段食管癌同步加量调强放疗技术的比较分析

目的 比较分析颈及上胸段食管癌不同射野数目同期加量调强放疗（SIB-IMRT）技术的剂量学参数,探讨优选方案。方法 对24例食管癌患者分别设计3、5、7、9四种不同照射野数的SIB-IMRT计划。PTV-G为大体肿瘤体积（GTV）外放1cm,PTV-C为临床靶体积（CTV）外放1cm,处方剂量分别为2.15 Gy／f和2 Gy／f, 28次, DT 60.2 Gy和56 Gy。通过剂量体积直方图（DVH）评估各靶区和危及器官的剂量学参数。结果 PTV-G 3、5、7、9野SIB-IMRT计划的靶区适形性指数（CI）和不均匀性指数（HI）分别为0.33、0.55、0.77、0.80和1.09、1.07、1.07、1.05,差异均有统计学意义（P＜0.05）;PTV-C 3、5、7、9野SIB-IMRT计划的靶区CI和HI分别为 0.69、0.71、0.72、0.79和1.22、1.13、1.075、1.073,差异均有统计学意义（P＜0.05）。3、5、7、9野脊髓最大剂量分别为4511.27、4288.31、4224.60和4201.43 cGy,差异有统计学意义（P＜0.05）。随着设野数目的增加,两肺的V5值增加,9野计划明显高于7野计划,分别为44.56％和32.36％（P＜0.05）;V20减小,9野计划与7野计划两者相似,分别为1928％和19.65％（P＞0.05）。结论 7野SIB-IMRT计划靶区剂量均匀,适形度高,对肺等重要器官的保护最佳,是颈段及上胸段食管癌SIB-IMRT治疗中优选的方案。     

食管癌调强放疗同期加量与序贯加量的研究

目的 比较食管癌调强放疗病变局部同期加量与序贯加量的疗效及不良反应。方法回顾分析2006-2015年河北医科大学第四医院收治的行根治性放化疗的330例初治食管癌患者的病历资料。根据治疗方法的不同分为同期加量组(135例)和序贯加量组(195例)。330例患者均接受淋巴引流区预防性照射,经倾向性评分配比(PSM)后,2个组各有105例患者入组。Kaplan-Meier法生存分析,Cox模型多因素预后分析。结果 PSM前同期加量组与序贯加量组1、3、5年局部控制率分别为80.1%、58.3%、46.7%与72.1%、44.9%、40.5%(P=0.050),总生存率分别为81.4%、51.9%、43.5%与80.5%、37.9%、22.3%(P=0.014)。PSM后同期加量组与序贯加量组1、3、5年局部控制率分别为80.2%、54.2%、43.9%与75.5%、47.2%、41.2%(P=0.264),总生存率分别为78.9%、49.0%、40.8%与83.3%、41.7%、24.8%(P=0.265)。多因素分析结果显示同期加量组中TNM分期为独立影响因素,而序贯加量组中TNM分期和化疗为独立影响因素。分层分析结果显示单纯放疗时同期加量组的局部控制率明显高于序贯加量组(P=0.018),总生存率也以同期加量组较高。结论 食管癌根治性放化疗同期加量与序贯加量调强放疗的局部控制率和总生存率基本一致,但单纯放疗时同期加量组的预后生存期明显优于序贯加量组,但仍需大宗病例的多中心研究结果予以佐证。