Effect of magnesium oxide on interfraction prostate motion and rectal filling in prostate cancer radiotherapy

Purpose

To investigate whether magnesium oxide reduces the interfraction motion of the prostate and the amount of rectal filling and rectal gas, which influences prostate position during radiotherapy for prostate cancer.

Patients and methods

From December 2008 to February 2010, 92 prostate cancer patients scheduled for intensity-modulated radiotherapy (77 Gy in 35 fractions) using fiducial marker-based position verification were randomly assigned to receive magnesium oxide (500 mg twice a day) or placebo during radiotherapy. In a previous study, we investigated the effect on intrafraction motion and did not find a difference between the treatment arms. Here, we compared the interfraction prostate motion between the two treatment arms as well as the amount of rectal filling and rectal air pockets using pretreatment planning computed tomography and magnetic resonance imagingscans.

Results

There was no statistically significant difference between the treatment arms in translation and rotation of the prostate between treatment fractions, except for the rotation around the cranial caudal axis. However, the difference was less than 1° and therefore considered not clinically relevant. There was no significant difference in the amount of rectal filling and rectal air pockets between the treatment arms.

Conclusion

Magnesium oxide is not effective in reducing the interfraction prostate motion or the amount of rectal filling and rectal gas during external-beam radiotherapy. Therefore, magnesium oxide is not recommended in clinical practice for these purposes.     

Intensity-modulated radiotherapy for neoadjuvant treatment of gastric cancer

Radiation therapy plays an integral role in the treatment of gastric cancer in the postsurgery setting, the inoperable/palliative setting, and, as in the case of the current report, in the setting of neoadjuvant therapy prior to surgery. Typically, anterior-posterior/posterior-anterior (AP/PA) or 3-field techniques are used. In this report, we explore the use of intensity-modulated radiotherapy (IMRT) treatment in a patient whose care was transferred to our institution after 3-field radiotherapy (RT) was given to a dose of 30 Gy at an outside institution. If the 3-field plan were continued to 50 Gy, the volume of irradiated liver receiving greater than 30 Gy would have been unacceptably high. To deliver the final 20 Gy, an opposed parallel AP/PA plan and an IMRT plan were compared to the initial 3-field technique for coverage of the target volume as well as dose to the kidneys, liver, small bowel, and spinal cord. Comparison of the 3 treatment techniques to deliver the final 20 Gy revealed reduced median and maximum dose to the whole kidney with the IMRT plan. For this 20-Gy boost, the volume of irradiated liver was lower for both the IMRT plan and the AP/PA plan vs. the 3-field plan. Comparing the IMRT boost plan to the AP/PA boost-dose range (<10 Gy) in comparison to the AP/PA plan; however, the IMRT plan irradiated a smaller liver volume within the higher dose region (>10 Gy) in comparison to the AP/PA plan. The IMRT boost plan also irradiated a smaller volume of the small bowel compared to both the 3-field plan and the AP/PA plan, and also delivered lower dose to the spinal cord in comparison to the AP/PA plan. Comparison of the composite plans revealed reduced dose to the whole kidney using IMRT. The V20 for the whole kidney volume for the composite IMRT plan was 30% compared to approximately 60% for the composite AP/PA plan. Overall, the dose to the liver receiving greater than 30 Gy was lower for the composite IMRT plan and was well below acceptable limits. In conclusion, our study suggests a dosimetric benefit of IMRT over conventional planning, and suggests an important role for IMRT in the neoadjuvant treatment of gastric cancer.     

Intensity-modulated radiotherapy for neoadjuvant treatment of gastric cancer

Radiation therapy plays an integral role in the treatment of gastric cancer in the postsurgery setting, the inoperable/palliative setting, and, as in the case of the current report, in the setting of neoadjuvant therapy prior to surgery. Typically, anterior-posterior/posterior-anterior (AP/PA) or 3-field techniques are used. In this report, we explore the use of intensity-modulated radiotherapy (IMRT) treatment in a patient whose care was transferred to our institution after 3-field radiotherapy (RT) was given to a dose of 30 Gy at an outside institution. If the 3-field plan were continued to 50 Gy, the volume of irradiated liver receiving greater than 30 Gy would have been unacceptably high. To deliver the final 20 Gy, an opposed parallel AP/PA plan and an IMRT plan were compared to the initial 3-field technique for coverage of the target volume as well as dose to the kidneys, liver, small bowel, and spinal cord. Comparison of the 3 treatment techniques to deliver the final 20 Gy revealed reduced median and maximum dose to the whole kidney with the IMRT plan. For this 20-Gy boost, the volume of irradiated liver was lower for both the IMRT plan and the AP/PA plan vs. the 3-field plan. Comparing the IMRT boost plan to the AP/PA boost-dose range (<10 Gy) in comparison to the AP/PA plan; however, the IMRT plan irradiated a smaller liver volume within the higher dose region (>10 Gy) in comparison to the AP/PA plan. The IMRT boost plan also irradiated a smaller volume of the small bowel compared to both the 3-field plan and the AP/PA plan, and also delivered lower dose to the spinal cord in comparison to the AP/PA plan. Comparison of the composite plans revealed reduced dose to the whole kidney using IMRT. The V20 for the whole kidney volume for the composite IMRT plan was 30% compared to approximately 60% for the composite AP/PA plan. Overall, the dose to the liver receiving greater than 30 Gy was lower for the composite IMRT plan and was well below acceptable limits. In conclusion, our study suggests a dosimetric benefit of IMRT over conventional planning, and suggests an important role for IMRT in the neoadjuvant treatment of gastric cancer.     

Image-guided radiotherapy and motion management in lung cancer

In this review, image guidance and motion management in radiotherapy for lung cancer is discussed. Motion characteristics of lung tumours and image guidance techniques to obtain motion information are elaborated. Possibilities for management of image guidance and motion in the various steps of the treatment chain are explained, including imaging techniques and beam delivery techniques. Clinical studies using different motion management techniques are reviewed, and finally future directions for image guidance and motion management are outlined.Image-guided radiotherapy (IGRT) implies the use of in-room imaging to localize the target with the aim of guiding the treatment beam to an accurate aim. Based on the images, compensating actions may be taken to adjust for variations found in the images. Variations can be of both rigid and non-rigid nature, and occur on different time scales. Specific to image guidance for radiotherapy in the lungs, is the phenomenon that breathing causes geometric anatomical changes to take place in the patient within the time scale of a radiotherapy fraction that are (more or less) predictable and cyclic. This phenomenon at the same time poses great challenges to implementation of image guidance for lung radiotherapy, as well as great opportunities. Over the last approximately 15 years, almost overwhelming attention has been given to this subject in particular in the radiotherapy physics society, and great technical advances have been made, which have changed the clinical practice of lung radiotherapy. This review systematically covers both technical aspects and clinical implementation of various strategies for image guidance in lung radiotherapy. Focus will be given to techniques aimed at compensating for breathing dynamics, although it should be stated now that a fully comprehensive review would be much too vast to fit in the space available in a single article.     

Hemostasis radiotherapy for gastric cancer: Usefulness of the gastric cancer to spleen apparent diffusion coefficient ratio

The hemostatic effect of radiation therapy on gastric cancer with bleeding is known. However, blood tests and endoscopes are mainly used to determine the therapeutic effect. Additionally, magnetic resonance imaging has been reported to be useful when needed because endoscopes are invasive. In this study, magnetic resonance diffusion-weighted imaging was used to evaluate the hemostatic effect of gastric cancer. The hemostatic effect and apparent diffusion coefficient value were correlated. The apparent diffusion coefficient value was also effective in salvage irradiation during rebleeding. Although the apparent diffusion coefficient value of gastric cancer did not change during rescue irradiation, the degree of hemostatic effect could be evaluated in more detail by using the ratio of the apparent diffusion coefficient values of diffusion-weighted imaging of gastric cancer and the spleen. In the future, it would be desirable to use diffusion-weighted imaging instead of endoscopy to evaluate the gastric cancer to spleen apparent diffusion coefficient ratio in a large number of cases.     

Retrospective audit of inter-fraction motion for pelvic node radiotherapy in prostate cancer patients

IntroductionPelvic lymph nodes move independently to the prostate. When delivering radiotherapy to prostate and pelvic lymph nodes, daily inter- and intra-fraction anatomical changes need to be accounted for. Planning target volume (PTV) margins, grown from the pelvic lymph node clinical target volume need to be determined, to account for this variation in position.MethodsTwenty patients who had daily online image guided radiotherapy to prostate and pelvic lymph nodes between April and December 2018 were selected. Ten pre-treatment verification images using cone beam CT from each patient were registered to pelvic bone anatomy, prostate soft tissue or fiducial markers and pelvic lymph node soft tissue to assess the accuracy of treatment delivery. Population systematic and random errors and PTV margins were calculated.ResultsPTV margins of 0.4 cm, 0.4 cm and 0.7 cm left–right (LR), superior–inferior (SI) and anterior–posterior (AP) respectively were derived for the pelvic lymph nodes when registering to prostate. PTV margins of 0.3 cm, 0.2 cm and 0.4 cm LR, SI and AP respectively were derived for the pelvic lymph nodes when registering to bone. There was a posterior systematic shift of the prostate during the treatment course.ConclusionThere is differential motion of pelvic lymph nodes to prostate and in the era of prostate and pelvic radiotherapy for patients with node positive prostate cancer; there is increasing importance in the accuracy of dose delivery to the involved lymph node. Hence, this group of patients may benefit from personalised radiotherapy PTV margins, especially if the involved pelvic lymph node is within the anterior part of the clinical target volume.Implications for practiceOptimisation of dose delivery to the pelvic lymph nodes when prioritising the prostate in prostate and pelvic lymph node image guided radiotherapy.     

Influence of high-definition multileaf collimator for three-dimensional conformal radiotherapy and intensity-modulated radiotherapy of prostate cancer

The focus of this work is to evaluate the dosimetric impact of treatment planning for three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiotherapy (IMRT) of prostate cancer using Varian/BrainLAB 120-leaf high-definition multileaf collimator (HD120 MLC) with 2.5 mm leaf width and Varian 120-leaf millennium multileaf collimator (M120 MLC) with 5 mm leaf width. We measured the leaf transmission and dosimetric leaf gap (DLG) of two multileaf collimator (MLC) systems using Farmer ionization chamber. The dosimetric impact of treatment planning for 3DCRT and IMRT of prostate cancer for ten clinical cases using two MLC systems was evaluated quantitatively. 3DCRT was divided to 3DCRT(middle) as fitting at middle of leaf tip and 3DCRT(outside) as fitting at outside of leaf tip. The leaf transmission factor and DLG of HD120 MLC for 6 and 10 MV X-ray decreased by 0.2% and 1 mm, respectively, compared to M120 MLC. The mean conformity index of PTV of treatment planning for prostate 3DCRT(middle), 3DCRT(outside) , and IMRT decreased by 0.9%, 6.6%, and 0.9% and the mean homogeneity index increased 2.3%, 13.0%, and 4.2%, respectively. The mean V20, V40, and V65 decreased by 2.4%, 6.6%, and 4.5% for bladder and 3.3%, 6.1%, and 5.9% for rectum, respectively. The results of this work demonstrated that the dose conformity of PTV improved and the dose of bladder and rectum decreased for 3DCRT and IMRT of prostate cancer using HD120 MLC compared to M120 MLC, because of reduction of leaf width, leaf transmission, and rounded leaf end transmission.     

A strategy for the use of image-guided radiotherapy (IGRT) on linear accelerators and its impact on treatment margins for prostate cancer patients

Background and Purpose

In external beam radiotherapy of prostate cancer, the consideration of various systematic error types leads to wide treatment margins compromising normal tissue tolerance. We investigated if systematic set-up errors can be reduced by a set of initial image-guided radiotherapy (IGRT) sessions.

Patients and Methods

27 patients received daily IGRT resulting in a set of 882 cone-beam computed tomographies (CBCTs). After matching to bony structures, we analyzed the dimensions of remaining systematic errors from zero up to six initial IGRT sessions and aimed at a restriction of daily IGRT for 10% of all patients. For threshold definition, we determined the standard deviations (SD) of the shift corrections and selected patients out of this range for daily image guidance. To calculate total treatment margins, we demanded for a cumulative clinical target volume (CTV) coverage of at least 95% of the specified dose in 90% of all patients.

Results

The gain of accuracy was largest during the first three IGRTs. In order to match precision and workload criteria, thresholds for the SD of the corrections of 3.5 mm, 2.0 mm and 4.5 mm in the left-right (L-R), cranial-caudal (C-C), and anterior-posterior (A-P) direction, respectively, were identified. Including all other error types, the total margins added to the CTV amounted to 8.6 mm in L-R, 10.4 mm in C-C, and 14.4 mm in A-P direction.

Conclusion

Only initially performed IGRT might be helpful for eliminating gross systematic errors especially after virtual simulation. However, even with daily IGRT performance, a substantial PTV margin reduction is only achievable by matching internal markers instead of bony anatomical structures.     

Postoperative radiotherapy for prostate cancer

Purpose

The aim of this work was to characterise actuarial incidence and prevalence of early and late side effects of local versus pelvic three-dimensional conformal postoperative radiotherapy for prostate cancer.

Materials and methods

Based on a risk-adapted protocol, 575 patients received either local (n = 447) or local-plus-pelvic (n = 128) radiotherapy. Gastrointestinal (GI) and genitourinary (GU) side effects (≥grade 2 RTOG/EORTC criteria) were prospectively assessed. Maximum morbidity, actuarial incidence rate, and prevalence rates were compared between the two groups.

Results

For local radiotherapy, median follow-up was 68 months, and the mean dose was 66.7?Gy. In pelvic radiotherapy, the median follow-up was 49 months, and the mean local and pelvic doses were 66.9 and 48.3?Gy respectively. Early GI side effects ≥ G2 were detected in 26% and 42% of patients respectively (p < 0.001). Late GI adverse events were detected in 14% in both groups (p = 0.77). The 5?year actuarial incidence rates were 14% and 14%, while the prevalence rates were 2% and 0% respectively. Early GU ≥ G2 side effects were detected in 15% and 16% (p = 0.96), while late GU morbidity was detected in 18% and 24% (p = 0.001). The 5?year actuarial incidence rates were 16% and 35% (p = 0.001), while the respective prevalence rates were 6% and 8%.

Conclusions

Despite the low prevalence of side effects, postoperative pelvic radiotherapy results in significant increases in the actuarial incidence of early GI and late GU morbidity using a conventional 4?field box radiotherapy technique. Advanced treatment techniques like intensity-modulated radiotherapy (IMRT) or volumetric modulated arc radiotherapy (VMAT) should therefore be considered in pelvic radiotherapy to potentially reduce these side effects.

     

立体定向放射治疗胰腺癌

目的 对立体定向放射治疗胰腺癌的临床意义进行评价。方法 对16例胰腺癌患者行立体定向放射治疗,病变体积26.5~116.5cm3,肿瘤边缘单次剂量为3~5Gy,治疗10~20次,每日1次,每周治疗5次,治疗后临床和影像手段随访。结果 治疗有效率(完全缓解+部分缓解)为81.2%,合并疼痛患者均有不同程度缓解,6/7患者黄疸消除,生存质量明显改善,中位生存期11个月,死亡原因多为远处转移;治疗副作用根据RTOG标准评价,68.7%患者有轻度早期反应,1例重度晚期反应。结论 立体定向放射治疗胰腺癌是有效的局部控制手段,可明显的缓解症状,改善患者生存质量,并且治疗的并发症可以被临床接受,但肿瘤的远处转移是影响患者生存的主要问题。     

Image-guided radiotherapy for prostate cancer

Purpose

To evaluate inter- and intrafraction organ motion with an ultrasound-based prostate localization system (BAT®) for patients treated with intensity-modulated radiotherapy for prostate cancer.

Patients and Methods

After set-up to external skin marks, 260/219 ultrasound-based alignments were performed before/after irradiation in 32 consecutive patients. Image quality was classified as good, satisfactory or poor. Patient- and imaging-related parameters were analyzed to identify predictors for poor image quality. Shifts in relation to the treatment planning computed tomography (CT) were recorded before/after irradiation in the superior-inferior (SI), anterior-posterior (AP) and right-left (RL) directions to determine inter-/intrafraction prostate motion.

Results

The thickness of tissue anterior to the bladder and bladder volume during the ultrasound localization as well as an inferior prostate position relative to public symphysis (determined in treatment planning CT) were found to be independent predictors of a poor image quality. Interfraction shifts (mean ± standard deviation: ?0.2 ± 4.8 [SI], 2.4 ± 6.6 [AP] and 1.9 ± 4.6 [RL]) varied much stronger than intrafraction shifts (0.0 ± 2.0 [SI], 0.6 ± 2.2 [AP] and 0.2 ± 1.9 [RL]). A larger pressure of the ultrasound probe (determined as a larger reduction of the distance abdominal skin to prostate between the planning CT and the ultrasound) was applied in case of poor image quality, associated with larger systematic posterior prostate displacements.

Conclusion

Intrafraction prostate shifts are considerably smaller in comparison to interfraction shifts. Bladder filling and a small pressure on the ultrasound probe are crucial to achieve an adequate image quality without systematic prostate displacements.     

Magnitude of observer error using cone beam CT for prostate interfraction motion estimation: effect of reducing scan length or increasing exposure

Objective:

Cone beam CT (CBCT) enables soft-tissue registration to planning CT for position verification in radiotherapy. The aim of this study was to determine the interobserver error (IOE) in prostate position verification using a standard CBCT protocol, and the effect of reducing CBCT scan length or increasing exposure, compared with standard imaging protocol.

Methods:

CBCT images were acquired using a novel 7 cm length image with standard exposure (1644 mAs) at Fraction 1 (7), standard 12 cm length image (1644 mAs) at Fraction 2 (12) and a 7 cm length image with higher exposure (2632 mAs) at Fraction 3 (7H) on 31 patients receiving radiotherapy for prostate cancer. Eight observers (two clinicians and six radiographers) registered the images. Guidelines and training were provided. The means of the IOEs were compared using a Kruzkal–Wallis test. Levene''s test was used to test for differences in the variances of the IOEs and the independent prostate position.

Results:

No significant difference was found between the IOEs of each image protocol in any direction. Mean absolute IOE was the greatest in the anteroposterior direction. Standard deviation (SD) of the IOE was the least in the left–right direction for each of the three image protocols. The SD of the IOE was significantly less than the independent prostate motion in the anterior–posterior (AP) direction only (1.8 and 3.0 mm, respectively: p = 0.017). IOEs were within 1 SD of the independent prostate motion in 95%, 77% and 96% of the images in the RL, SI and AP direction.

Conclusion:

Reducing CBCT scan length and increasing exposure did not have a significant effect on IOEs. To reduce imaging dose, a reduction in CBCT scan length could be considered without increasing the uncertainty in prostate registration. Precision of CBCT verification of prostate radiotherapy is affected by IOE and should be quantified prior to implementation.

Advances in knowledge:

This study shows the importance of quantifying the magnitude of IOEs prior to CBCT implementation.     

Influence of radiotherapy on lymphocyte subpopulations

The authors investigated the effects of radiation therapy on the immune system by studying lymphocyte subsets and other parameters in 32 patients undergoing radiation therapy for solid cancer. With monoclonal antibody techniques, we studied both T- and B-lymphocytes; cell suspensions were analyzed by means of a Facs Spectrum III Ortho (Ortho-Diagnostic) unit. The first control was performed right after the beginning of radiotherapy, when the dose to the patients was 50 Gy or higher. The second control was performed at 40 Gy because all patients received this dose. 30% of the patients exhibited lymphopenia from the beginning of the study; at 40 Gy the number of T-lymphocytes was low and helper/suppressor ratio was altered. A variable response of B-cells was observed, although all patients exhibited restoration of normal values at 6 months. Four patients only suffered from side-effects: a patient with tongue cancer presented oral mycosis, and a woman--treated for breast cancer--presented vaginal mycosis. Two cases of cystitis were also observed, after 18 Gy, in patients with uterine carcinoma undergoing pelvic irradiation. Disease progression was observed in 2 patients with head and neck cancer, while 3 patients died from lung cancer progression. Another one, with head and neck cancer, died because of heart failure.     

Four-dimensional cone-beam computed tomography-guided radiotherapy for gastric lymphoma

Purpose

We describe a treatment method with four-dimensional cone-beam computed tomography (4D-CBCT)-guided radiotherapy for gastric lymphoma.

Materials and methods

We performed image-guided radiotherapy (IGRT) with 15 fractions for a gastric mucosa-associated lymphoid tissue lymphoma patient, using 4D-CBCT. The stomach was delineated based on 4D-CT images. For image guidance, an automatic registration between planning CT and 4D-CBCT images was performed based on the bony anatomy (bone matching), followed by manual registration based on the stomach in 4D-CBCT images of all 10 phases (4D matching). We calculated the covering ratio (CR) with variable stomach-to-planning target volume (PTV) margins, based on the images of all phases [CR (%) = the number of covering phases/all 150 phases × 100].

Results

The patient underwent radiotherapy (RT) as scheduled, without any significant adverse effects. The appropriate PTV margins (CR ≥ 95%) were 25 mm (CR 99.3%) and 15 mm (CR 98.7%) for bone and 4D matching, respectively.

Conclusion

4D matching using 4D-CBCT is appropriate for IGRT of gastric lymphomas.

     

Indications for radiotherapy of rectal cancer

Surgery and radiotherapy complete each other in local control of suffering from rectal carcinoma. A radiotherapeutic effect on tumor is secured often. The adjuvant radiotherapy is the most interesting indication, though the most controversial as present too. Analysing all data and with experiences of an own irradiation study we have not any doubt that the indication is qualified for a combined therapy, if the therapeutic aim with priority is to prevent a local relapse as the most frequent and complained of form of therapeutic failure. In this problem, radical irradiation forms, as pre- and accumulating irradiation (sandwich-technique) and after-irradiation, render superior to an exclusive pre irradiation. In result of this study we practise a preirradiation of 25 Gy with immediately following operation and an accumulating irradiation to 50 Gy in proved high-risk-stage (T greater than or equal to 3 NoMo,Tx N1-3 Mo). If there is a primary local incurability by tumor invasion into the neighbourhood a pre-irradiation is done with 50 Gy and following explorative laparatomy within 4-6 weeks. Nearly 60% of these tumors become operable after that. Likewise we practise in unirradiated patients with locoregional tumor recurrence. Also here the extirpation quota of patients with general or systemic incurability, that a stoma construction is required in, we carry out a transanal tumor reduction and irradiate with 50 Gy after that. Especially this therapeutic principle has proved its worth in patients that are past eighty. Here with acceptable living quality and avoiding a stoma construction a survival can be reached that corresponds to the statistical survival of this stage of life.     

63例老年胃癌患者的放疗安全性评估

目的 探讨老年胃癌患者放疗的安全性。方法 回顾性分析2009年3月-2014年12月63例≥70岁）、接受放疗及放化疗的胃癌患者,均经病理确诊。男性48例,女性15例,中位年龄74（70~85）岁,分期Ⅰ_b~Ⅳ期,中位放疗剂量50（16~60）Gy,中位放疗时间36（11~73）d,同期联合以氟尿嘧啶类为基础的化疗或不联合。观察患者治疗完成情况、不良反应、症状控制、近期疗效及1、2年生存率。比较同期放化疗组和单纯放疗组的生存和治疗耐受情况。结果 63例患者中,81.0%（51/63）的患者按计划完成放疗。19.0%（12/63）的患者出现3、4级不良反应,其中血液毒性占9.5%（6/63）,胃肠道反应发生率9.5%（6/63）。56例近期疗效可评价,其中7.1%（4/56）完全缓解（CR）,39.3%（22/56）部分缓解（PR）,39.3%（22/56）疾病稳定（SD）。中位随访时间13.75个月（1.5~69个月）,中位生存时间17个月（95%CI6.9~21.1）,1、2年总生存（OS）率分别为55.0%（95%CI 48.6% ~61.4%）及36.2%（95%CI29.2% ~43.2%）。同期放化疗组和单纯放疗组的中位生存时间分别为20.5和12个月,差异无统计学意义（P>0.05）。两组严重不良反应发生情况的差异亦无统计学意义（P>0.05）。结论 多数老年胃癌患者能耐受放疗和放化疗,不良反应在允许范围内,并且有一定的疗效。     

早期胃癌淋巴结转移的影响因素分析

目的探讨早期胃癌淋巴结转移的影响因素。方法回顾性分析38例有淋巴结转移和166例无淋巴结转移的早期胃癌患者的临床资料,分析两组患者在各指标上的差异。结果肿瘤大小、大体类型、组织学类型、病理类型和浸润深度是早期胃癌淋巴结转移的影响因素,其中组织学类型的影响最大（OR=16．96）。结论了解早期胃癌淋巴结转移的影响因素,对于正确判断和预测早期胃癌的淋巴结转移,以及采取干预措施有重要的意义。