Target tailoring and proton beam therapy to reduce small bowel dose in cervical cancer radiotherapy

Purpose

The aim of the study was to investigate the potential clinical benefit from both target tailoring by excluding the tumour-free proximal part of the uterus during image-guided adaptive radiotherapy (IGART) and improved dose conformity based on intensity-modulated proton therapy (IMPT).

Methods

The study included planning CTs from 11 previously treated patients with cervical cancer with a >4-cm tumour-free part of the proximal uterus on diagnostic magnetic resonance imaging (MRI). IGART and robustly optimised IMPT plans were generated for both conventional target volumes and for MRI-based target tailoring (where the non-invaded proximal part of the uterus was excluded), yielding four treatment plans per patient. For each plan, the V_15Gy, V_30Gy, V_45Gy and D_mean for bladder, sigmoid, rectum and bowel bag were compared, and the normal tissue complication probability (NTCP) for ≥grade 2 acute small bowel toxicity was calculated.

Results

Both IMPT and MRI-based target tailoring resulted in significant reductions in V_15Gy, V_30Gy, V_45Gy and D_mean for bladder and small bowel. IMPT reduced the NTCP for small bowel toxicity from 25% to 18%; this was further reduced to 9% when combined with MRI-based target tailoring. In four of the 11 patients (36%), NTCP reductions of >10% were estimated by IMPT, and in six of the 11 patients (55%) when combined with MRI-based target tailoring. This >10% NTCP reduction was expected if the V_45Gy for bowel bag was >275?cm³ and >200?cm³, respectively, during standard IGART alone.

Conclusions

In patients with cervical cancer, both proton therapy and MRI-based target tailoring lead to a significant reduction in the dose to surrounding organs at risk and small bowel toxicity.

     

Normal liver tissue change after proton beam therapy

Purpose

Normal liver tissue changes after proton beam therapy (PBT) were investigated in patients at 1 and 2 years after the therapy.

Materials and methods

Changes in normal liver tissue volume were examined. The dose distribution of the normal liver tissue was also simulated on the follow-up CTs.

Results

The normal liver tissue volume was 1149?±?215 cm³ before treatment, 1089?±?188 cm³ at 1 year, and 1080?±?236 cm³ at 2 years after treatment. The normal liver tissue volume was increased in 10 and decreased in 20 patients at 2 years and was smaller than that before the treatment in total (P?=?0.03). The simulated volume that received more than 30 Gray equivalent [V30 (cm³)] at 1 year was 258?±?187 cm³ and that at 2 years (244?±?171 cm³) was smaller than that before treatment (297?±?140 cm³) (P?=?0.03).

Conclusions

The changes in the shape and volume of normal liver tissue are not constant, which cause a large dose distribution discrepancy in the normal liver for 2 years. Therefore, careful consideration of the dose distribution of normal liver tissue is required when planning re-irradiation.

     

Quality assurance evaluation of spot scanning beam proton therapy with an anthropomorphic prostate phantom

Objective:

The purpose of this study was to evaluate spot scanning proton therapy with an anthropomorphic prostate phantom at the Proton Therapy Center of The University of Texas MD Anderson Cancer Center at Houston, TX (PTCH).

Methods:

An anthropomorphic prostate phantom from the Radiological Physics Center (RPC), The University of Texas MD Anderson Cancer Center, Houston, TX, was used, which contained thermoluminescent dosemeters and GAFCHROMIC^® EBT2 film (ISP Technologies, Wayne, NJ). The phantom was irradiated by the Hitachi synchrotron (Hitachi America, Ltd, Tarrytown, NY), and the results were compared between the treatment planning system (TPS) and RPC measurements.

Results:

RPC results show that the right/left, inferior/superior and posterior/anterior aspects of the coronal/sagittal and EBT2 film measurements were within ±7%/±4 mm of the TPS. The RPC thermoluminescent dosemeter measurements of the prostate and femoral heads were within 3% of the TPS.

Conclusion:

The RPC prostate phantom is a useful mechanism to evaluate spot scanning beam proton therapy within certain confidence levels.

Advances in knowledge:

The RPC anthropomorphic prostate phantom could be used to establish quality assurance of spot scanning proton beam for patients with prostate cancer.During the past decade, the use of proton beams in the treatment of cancer has increased. Passive scattering has been the most common technique for delivery of proton beams. Passive scattering uses range modulation wheels with a combination of field shaping apertures and compensators to deliver a uniform dose distribution to the target [1–4]. Until recently, the proton scanning technology has only been available at one facility, namely the Paul Scherrer Institute in Switzerland [5]. The spot-scanning beam at the Paul Scherrer Institute moves only along the longitudinal axis and is combined with a moving couch. The scanning proton beams confine the dose distribution to the target volume by depositing the dose using pencil beams of different energies to deliver the dose without using any scattering or range-modulating devices [6]. This is considered an improvement with respect to passively scattered proton beams because there are no apparatuses in the beam path to produce contamination by neutrons [7].The principle of scanning beam is simple and is based on the fact that protons, being charged particles, are subject to Lorentz forces. That is, when subjected to an electric field, protons are accelerated, and when subjected to a magnetic field, protons are deflected. In depth, the Bragg peaks are stacked by altering the proton energy. Through this combination of scanning and energy variation, the Bragg peak can be effectively placed anywhere within the target in three dimensions. Dose uniformity is then achieved by a treatment planning optimisation of the individual fluences of each pencil beam [8]. The Radiological Physics Center (RPC), The University of Texas MD Anderson Cancer Center, Houston, TX, has several anthropomorphic phantoms, which are used as part of the credentialing services for participation in the National Cancer Institute (NCI, at the National Institutes of Health, Bethesda, MD) sponsored clinical trials. The pelvis phantom was originally designed to be of mailable quality assurance to test intensity-modulated radiation therapy (IMRT) procedures. With this in mind, the design and materials were chosen to simulate the pelvis region of a patient with the anatomy present to create restrictions for treatment planning and delivery in typical IMRT cases. The relative stopping power of each material is used to construct the phantom to verify the tissue equivalence of the materials used. In the treatment of prostate cancer, the Proton Therapy Center at Houston, TX (PTCH), uses two opposing beams. Previously, RPC used a prostate phantom for passive scattering proton beam and found that by using an appropriate value of relative stopping power, the prostate phantom could be used to evaluate proton passive beam therapy. The evaluation of spot scanning is a new challenge. Therefore, the purpose of this study was to evaluate spot scanning for prostate therapy using the RPC phantom.     

质子治疗计划系统剂量算法的研究进展

质子治疗具有肿瘤区域剂量适形度高,周围危及器官所受辐射少的特点,对于减少患者的放疗辐射损伤具有重要的意义。准确地计算出患者体内的剂量分布是质子精准治疗的必要条件,因此,质子治疗计划系统是质子治疗中不可或缺的关键部分。本文对质子治疗计划系统及其所使用的剂量算法的研究进展进行综述。     

Severe complications after hypofractionated high dose rate intracavitary brachytherapy following external beam irradiation for oesophageal carcinoma

The purpose of this study was to evaluate severe complications that developed after high dose rate (HDR) intracavitary brachytherapy for oesophageal carcinoma. Six consecutive patients with oesophageal carcinoma were treated by external beam irradiation (60 Gy in 30 fractions over 6 weeks) followed by hypofractionated intracavitary HDR brachytherapy (10 Gy in 2 fractions). Two of the six patients were alive and well for more than 2-3 years following therapy, but three of the six patients developed treatment-related oesophageal fistulae and died. HDR intracavitary brachytherapy following external beam irradiation is an effective method for radical treatment of oesophageal carcinoma. However, hypofractionated HDR brachytherapy should be used with care.     

Reirradiation for recurrent malignant brain tumor with radiotherapy or proton beam therapy

Background and purpose

Radiotherapy for recurrent malignant brain tumors is usually limited because of the dose tolerance of the normal brain tissue. The goal of the study was to evaluate the efficacy and feasibility of reirradiation for patients with recurrent malignant brain tumors.

Patients and methods

The subjects comprised 26 patients with recurrent malignant brain tumors treated with conventional radiotherapy (RT, n?=?8), stereotactic radiotherapy (SRT, n?=?10), and proton beam therapy (PBT, n?=?8) at our institute. Fifteen patients had glioblastoma, 6 had WHO grade 3 glioma, and 5 had other tumors. The dose of initial radiotherapy was 34.5–94.4 Gy. Different radiation schedules were compared using the equivalent dose in 2-Gy fractions.

Results

Reirradiation was completed in all patients without a severe acute reaction. The reirradiation doses were 30–60 Gy (median, 42.3 Gy) and the total doses for the initial and second treatments were 64.5–150.4 Gy (median, 100.0 Gy). Currently, 11 patients are alive (median follow-up period, 19.4 months) and 15 are dead. The median survival and local control periods after reirradiation of the 26 patients were 18.3 and 9.3 months, respectively. For the 15 patients with glioblastoma, these periods were 13.1 and 11.0 months, respectively. Two patients showed radiation necrosis that was treated by surgery or conservative therapy.

Conclusion

Reirradiation for recurrent malignant brain tumor using conventional RT, SRT, or PBT was feasible and effective in selected cases. Further investigation is needed for treatment optimization for a given patient and tumor condition.     

Spot-scanning beam proton therapy vs intensity-modulated radiation therapy for ipsilateral head and neck malignancies: A treatment planning comparison

Radiation therapy for head and neck malignancies can have side effects that impede quality of life. Theoretically, proton therapy can reduce treatment-related morbidity by minimizing the dose to critical normal tissues. We evaluated the feasibility of spot-scanning proton therapy for head and neck malignancies and compared dosimetry between those plans and intensity-modulated radiation therapy (IMRT) plans. Plans from 5 patients who had undergone IMRT for primary tumors of the head and neck were used for planning proton therapy. Both sets of plans were prepared using computed tomography (CT) scans with the goals of achieving 100% of the prescribed dose to the clinical target volume (CTV) and 95% to the planning TV (PTV) while maximizing conformity to the PTV. Dose-volume histograms were generated and compared, as were conformity indexes (CIs) to the PTVs and mean doses to the organs at risk (OARs). Both modalities in all cases achieved 100% of the dose to the CTV and 95% to the PTV. Mean PTV CIs were comparable (0.371 IMRT, 0.374 protons, p = 0.953). Mean doses were significantly lower in the proton plans to the contralateral submandibular (638.7 cGy IMRT, 4.3 cGy protons, p = 0.002) and parotid (533.3 cGy IMRT, 48.5 cGy protons, p = 0.003) glands; oral cavity (1760.4 cGy IMRT, 458.9 cGy protons, p = 0.003); spinal cord (2112.4 cGy IMRT, 249.2 cGy protons, p = 0.002); and brainstem (1553.52 cGy IMRT, 166.2 cGy protons, p = 0.005). Proton plans also produced lower maximum doses to the spinal cord (3692.1 cGy IMRT, 2014.8 cGy protons, p = 0.034) and brainstem (3412.1 cGy IMRT, 1387.6 cGy protons, p = 0.005). Normal tissue V₁₀, V₃₀, and V₅₀ values were also significantly lower in the proton plans. We conclude that spot-scanning proton therapy can significantly reduce the integral dose to head and neck critical structures. Prospective studies are underway to determine if this reduced dose translates to improved quality of life.     

Effectiveness and safety of proton beam therapy for advanced hepatocellular carcinoma with portal vein tumor thrombosis

Purpose

To evaluate the clinical effectiveness and safety of proton beam therapy (PBT) in advanced hepatocellular carcinoma (HCC) patients with portal vein tumor thrombosis (PVTT).

Patients and methods

Twenty-seven HCC patients with PVTT underwent PBT, including 22 patients with modified International Union Against Cancer (mUICC) stage IVA,five patients with stage IVB primary tumors, and 16 with main PVTT. A median dose of 55 GyE (range, 50–66 GyE) in 20–22 fractions was delivered to a target volume encompassing both the PVTT and primary tumor.

Results

Overall, treatment was well tolerated, with no toxicity of grade ≥?3. Median overall survival (OS) times in all patients and in stage IVA patients were 13.2 months and 16 months, respectively. Assessments of PVTT response showed complete response in 0 of 27 (0?%) patients, partial response in 15 (55.6?%), stable disease in 10 (37?%), and progressive disease in 2 (7.4?%) patients, with an objective response rate of 55.6?%. PVTT responders showed significantly higher actuarial 1-year local progression-free survival (LPFS; 85.6?% vs. 51.3?%), relapse-free survival (RFS; 20?% vs. 0?%) and OS (80?% vs. 25?%) rates than nonresponders (p?Conclusion Our data suggest that PBT could improve LPFS, RFS, and OS in advanced HCC patients with PVTT and it is feasible and safe for these patients.     

Definitive proton beam radiation therapy for inoperable gastric cancer: a report of two cases.

Proton beam radiation therapy using 250 MeV protons was carried out on two patients with early gastric cancer (T1, N0, M0). One patient was an 85-year-old man with early gastric cancer of type IIa + IIc. The other one was a 70 year old man with early gastric cancer of type IIc. In both cases histological examination of biopsy specimens showed differentiated adenocarcinoma; distant metastasis was not found by other examinations. Both patients were considered inoperable due to their poor cardiac and/or respiratory functions. Therefore, it was decided to treat them by definitive proton irradiation, delivering total doses of 86 Gy and 83 Gy, respectively. In both patients, skin erythema that did not require any special treatment was found in the irradiation field. Hematobiological examinations did not show any abnormality. Although endoscopic examination at two years after irradiation in the former case and at seven months in the latter case showed persistent gastric ulcer at the site of the cancerous lesions, cancer cells were not found histologically. Therefore, we concluded that proton irradiation therapy was useful for inoperable early gastric cancers.     

Feasibility study of radiophotoluminescent glass rod dosimeter postal dose intercomparison for high energy photon beam

A radiophotoluminescent glass rod dosimeter (GRD) system has recently become commercially available. In this study we evaluated whether the GRD would be suitable for external dosimetric audit program in radiotherapy. For this purpose, we introduced a methodology of the absorbed dose determination with the GRD by establishing calibration coefficient and various correction factors (non-linearity dose response, fading, energy dependence and angular dependence). A feasibility test of the GRD postal dose intercomparison was also performed for eight high photon beams by considering four radiotherapy centers in Korea. In the accuracy evaluation of the GRD dosimetry established in this study, we obtained within 1.5% agreements with the ionization chamber dosimetry for the ⁶⁰Co beam. It was also observed that, in the feasibility study, all the relative deviations were smaller than 3%. Based on these results, we believe that the new GRD system has considerable potential to be used for a postal dose audit program.     

头颈部恶性肿瘤放疗后颈动脉狭窄的研究进展

头颈部恶性肿瘤是常见的恶性肿瘤,放射治疗是头颈部恶性肿瘤的重要治疗手段之一。随着治疗手段的进步,患者生存期明显延长,同时放疗引起的颈动脉狭窄也越来越受到医生及患者的关注。放疗引起的颈动脉狭窄是多种因素作用的结果,目前应用比较广泛的检查手段为彩色超声多普勒及颈动脉听诊,经皮血管成形术及支架植入术为主要的治疗手段。笔者主要针对头颈部恶性肿瘤放疗后引起颈动脉狭窄的发病率、发病机制、相关危险因素、诊断及治疗原则等方面进行综述。     

Defining dose constraints for catheter insertion sites to minimize toxicity after interstitial breast brachytherapy

PurposeThe purpose of this study was to define dose constraints for catheter insertion sites to minimize probability of prominent post-therapy skin marks after interstitial breast brachytherapy.Methods and MaterialsForty patients who had undergone interstitial breast brachytherapy were studied at followup at least 2 years after the procedure. Their implant marks were compared with background skin and areola and scored as Gr0 = invisible (same color as surrounding skin), Gr1 = darker than surrounding skin but lighter than areola or hypopigmentation, and Gr2 = same color as areola or darker. Highest point doses received in each plane of implant and their corresponding closest distances from clinical target volume, 85% isodose, and closest catheter dwell point were used for analysis. A logistic regression was performed to ascertain effects of various dosimetric parameters on the probability of Gr2 marks. Receiver operating characteristic curve was generated to derive cutoffs.ResultsA total of 280 dose points were studied. Median values for various parameters were 1.4 Gy (0.24–3.74) for Dose max and 1.6 cm, 1.5 cm, and 1.0 cm for Dist CTV min, Dist Iso min, and Dist Dwell min, respectively. On logistic regression, increasing Dose max alone was associated with an increased likelihood of developing Gr2 marks. Each unit increase of Dose max increased probability of development of Gr2 skin marks by 5.0% (2.391–10.328). Receiver operating characteristic analysis also showed greatest odd ratio (8.0), sensitivity (74.8%), and specificity (73%) for Dose max.ConclusionsIt seems prudent to restrict dose to catheter insertion sites for better cosmesis.