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.     

Radiation injury of the lung after three-dimensional conformal radiation therapy

OBJECTIVE: The objective of this study is to describe the CT patterns of radiation injury in the lungs of patients who have undergone three-dimensional (3D) conformal radiation therapy (CRT). MATERIALS AND METHODS: Over a 36-month period, the chest CT scans of 19 patients with non-small cell lung cancer who were treated with 3D CRT were reviewed. CT scans were evaluated for findings of radiation injury (ground-glass opacities, consolidation, bronchiectasis, and volume loss). The presence, extent, and distribution of these findings were reached by consensus. RESULTS: Radiation pneumonitis limited to a small area immediately around the tumor was present in all patients who were imaged within 3 months after completion of the treatment (n = 7). Radiation-induced fibrosis occurred in all patients (n = 19). Three distinct patterns of fibrosis were consistently present, and these were classified as modified conventional, masslike, and scarlike. Modified conventional fibrosis (consolidation, volume loss, and bronchiectasis similar to, but less extensive than, conventional radiation fibrosis) was seen in five patients. Masslike fibrosis (focal consolidation with traction bronchiectasis limited to the site of the original tumor) was seen in eight patients. Scarlike fibrosis (linear opacity in the region of the original tumor associated with moderate to severe volume loss) was seen in six patients. CONCLUSION: Three-dimensional conformal radiation therapy results in three patterns of radiation fibrosis that differ from the conventional radiation-induced lung injury. Knowledge of the full spectrum of these manifestations is useful in the correct interpretation of CT scans after 3D CRT.     

Erectile dysfunction after prostate three-dimensional conformal radiation therapy

Purpose

Erectile dysfunction is associated with all the common treatment options for prostate cancer. The aim of this research was to evaluate the relationship between erectile function and radiation dose to the penile bulb (PB) and other proximal penile structures in men receiving conformal radiotherapy (CRT) without hormonal therapy (HT) for prostate cancer, whose sexual function was known before treatment.

Patients and methods

The study included 19 patients treated with 3D-CRT for localized prostate cancer at our department, who were self-reported to be potent before treatment, had not received HT, and had complete follow-up data available. Our evaluation was based on the International Index of Erectile Function (IIEF-5). Dose–volume histograms (DVHs) were used to evaluate the dose to the PB. Statistical analysis was performed with an unconditional logistic regression model.

Results

All patients reported change in potency after radiation. Eight patients (42%) remained potent but showed a decrease of 1 or 2 levels of potency, as defined by the IIEF-5 questionnaire (reduced potency group), while 11 patients (58%) reported a change of higher levels and revealed a severe erectile dysfunction after 2?years (impotence group). Multivariate analysis of morphological and dosimetric variables yielded significance for the mean dose (p?=?0.05 with an odds ratio of 1.14 and 95% CI 1–1.30). Patients receiving a mean dose of less than 50?Gy to the PB appear to have a much greater likelihood of maintaining potency.

Conclusion

Our data suggest a possible existence of a dose–volume correlation between the dose applied to the PB and radiation-induced impotence.     

Evaluation of lung injury after three-dimensional conformal stereotactic radiation therapy for solitary lung tumors: CT appearance

PURPOSE: To evaluate the computed tomographic (CT) appearance of tumors and lung injury in patients who have undergone stereotactic radiation therapy (SRT) for solitary lung tumors. MATERIALS AND METHODS: Twenty-seven patients with primary lung cancer and four with metastatic lung cancer who underwent SRT for solitary lung tumors were enrolled for evaluation. SRT was delivered by using a three-dimensional conformal technique with a stereotactic body frame. A total dose of 48 Gy was administered in four fractions during a period of 2 weeks. After SRT, follow-up CT images were obtained every 2-3 months. Radiation-induced pulmonary injuries were classified into four patterns on CT images. The minimal lung dose to areas demonstrating pulmonary injury at CT was evaluated, and the correlation between the dose and the percentage volume of the whole lung irradiated by more than 20 Gy in total (V20) was assessed by using Spearman rank correlation. RESULTS: Tumor shrinkage continued for 2-15 months after SRT. Asymptomatic changes in the irradiated lung were noted at CT in all patients within 2-6 months (median, 4 months) after SRT. As the pattern at pulmonary CT changed, patchy consolidation was more predominantly seen as an acute change than were slight homogeneous increase in opacity, discrete consolidation, or solid consolidation; solid consolidation was the more predominantly seen late change. The minimal lung dose to the area demonstrating pulmonary injury in each patient ranged between 16 and 36 Gy (median, 24 Gy). The dose was significantly (P <.001) inversely correlated with the V20 in each patient. CONCLUSION: The reaction to SRT of the lungs seems similar to the reaction to conventional radiation therapy.     

Australian and New Zealand three-dimensional conformal radiation therapy consensus guidelines for prostate cancer

Three-dimensional conformal radiation therapy (3DCRT) has been shown to reduce normal tissue toxicity and allow dose escalation in the curative treatment of prostate cancer. The Faculty of Radiation Oncology Genito-Urinary Group initiated a consensus process to generate evidence-based guidelines for the safe and effective implementation of 3DCRT. All radiation oncology departments in Australia and New Zealand were invited to complete a survey of their prostate practice and to send representatives to a consensus workshop. After a review of the evidence, key issues were identified and debated. If agreement was not reached, working parties were formed to make recommendations. Draft guidelines were circulated to workshop participants for approval prior to publication. Where possible, evidence-based recommendations have been made with regard to patient selection, risk stratification, simulation, planning, treatment delivery and toxicity reporting. This is the first time a group of radiation therapists, physicists and oncologists representing professional radiotherapy practice across Australia and New Zealand have worked together to develop best-practice guidelines. These guidelines should serve as a baseline for prospective clinical trials, outcome research and quality assurance.     

剂量体积直方图参数对放射性肺炎的工作特征曲线预测分析

目的 应用受试者工作特征曲线(ROC)对剂量体积直方图参数(DVH)预测放射性肺炎(RP)进行分析,探究DVH参数预测RP的准确性(ACC)、敏感性(SEN)和特异性(SPE)。方法 收集118例接受三维适形调强放疗和化疗的非小细胞肺癌患者资料,回顾分析三维放疗计划系统中双肺V₅、V₁₀、V₁₃、V₂₀、V₃₀ (V_x为接受≥x Gy的相对肺体积) 和平均肺剂量 (MLD) 与治疗后出现≥2级RP (CTCAE3.0) 的相关性。对上述DVH参数应用ROC曲线进行回顾性分析,确定预测RP的ACC、SEN和SPE。结果 单因素分析显示,双肺V₅、V₁₀、V₁₃、V₂₀和MLD均与RP发生显著相关(χ²=4.786、5.771、6.366、7.367、6.945,P<0.05);双肺V₃₀、患者因素(年龄、性别、KPS评分、肿瘤位置、病理类型)和治疗因素(放疗总剂量、照射技术、化疗方案、化疗时机)与RP的发生风险无显著相关性。多因素分析显示双肺V₂₀与RP发生风险相关(χ²=10.96,OR=4.16, 95%CI 1.40~12.36,P<0.05),与其他DVH参数具有显著共线性(r=0.767~0.902,P<0.05)。ROC曲线证实双肺V₂₀能够预测RP的发生(Z=2.038,P<0.05),其预测的ACC、SEN和SPE分别为0.645(95%CI 0.498~0.793),0.650(95%CI 0.408~0.864) 和0.674(95%CI 0.571~0.765),其阳性预测值仅为28.9%。结论 双肺V₂₀与RP的发生风险相关,能够预测RP的发生,但是预测能力有限。     

三维适形放疗食管癌所致放射性肺炎相关因素分析

目的分析三维适形放疗食管癌患者的临床物理参数，为进一步优化食管癌适形放疗计划，减少放射性肺炎的发生提供参考标准。方法回顾性总结55例食管癌患者的三维适形治疗计划及临床资料，并对相关因素进行单因素、多因素的统计分析。结果55例中发生放射性肺炎12例，其中2级9例，3级3例。与放射性肺炎相关的因素有二程放疗、总剂量、后半程射野数、总射野数、肺V10、肺V15、肺V20、肺V25、肺D平均、食管GTVV50。Logistic多元回归分析显示二程放疗、后半程射野数、肺V25为放射性肺炎发生的独立影响因素。结论食管癌二程放疗、后半程射野数、肺V25系影响放射性肺炎发生的主要因素。     

非小细胞肺癌三维适形放疗后急性放射性食管炎相关剂量学因素分析

目的 探讨非小细胞肺癌(NSCLC)三维适形放疗后放射性食管炎发生的相关因素,为NSCLC三维适形治疗计划的制定提供参考指标。方法 收集2000年8月至2004年12月符合入组条件在本科接受三维适形放疗的NSCLC患者104例,其中鳞癌45例,腺癌20例,针吸活检或气管镜刷片找到癌细胞者33例,未获得病理确诊者6例。其中全程三维适形放疗者46例,58例前程先行传统常规放疗后程再行三维适形放疗。全组患者处方剂量范围60～78Gy,中位剂量66Gy。变量间的相关性分析采用Spearman相关性检验,组间比较采用χ²检验,Logistic方法进行多元回归分析。结果 本组患者放射性食管炎的发生率为46.2%,其中1级32例占30.8%,2级15例占14.4%,3级1例占1.0%。相关性分析表明食管接受的最大剂量、食管接受的平均剂量、照射野内的食管体积、食管V₄₀、V₄₅、V₅₀、V₅₅、V₆₀、LETT₄₅、LETT₅₀、LETT₅₅、LETT₆₀与放射性食管炎的发生呈正相关,多因素分析显示食管接受的最大剂量是≥2级放射性食管炎发生的独立性影响因素。结论 食管接受的最大剂量、平均剂量、照射野内食管体积、食管V₄₀～V₆₀、食管LETT₄₅～LETT₆₀与放射性食管炎的发生呈正相关,尤其食管接受的最大剂量对预测放射性食管炎发生有一定参考价值。     

局部晚期非小细胞肺癌三维适形放疗所致放射性食管炎的相关因素

目的：观察局部晚期非小细胞肺癌（ NSCLC）三维适形放疗所致放射性食管炎的相关影响因素。方法回顾性分析2001年1月至2008年12月期间接受放疗的局部晚期非小细胞肺癌203例,其中男性163例,女性40例,中位年龄63岁;Ⅲa期79例,Ⅲb期124例;中位等效处方剂量62 Gy（范围50～78 Gy）,其中,单纯放疗74例,序贯放化疗45例,同期放化疗87例。急性放射性食管炎采用美国肿瘤放射治疗协作组（ RTOG）标准,剂量体积直方图（ DVH）评估物理参数。对与放射性食管炎相关的临床因素及物理参数进行相关性分析。结果203例局部晚期NSCLC放疗后,发生1级急性放射性食管炎者47例,2级37例,3级4例,≥2级放射性食管炎发生率为20?2％（41/203）。单因素分析表明,年龄、化疗（单纯放疗/序贯放化疗/同期放化疗）、GTV、PTV、PTV和肺的平均剂量、食管最大剂量和平均剂量、食管V40、V45、V50、V55、V60、全周食管接受剂量＞45 Gy的食管长度（LETT45）和LETT50与≥2级放射性食管炎相关（r＝-0?162～0?235,P＜0?05）;而性别、肿瘤位置、吸烟与否、T、N分期、临床分期、放疗剂量、分割方式、GTV平均剂量、LETT55、LETT60与≥2级放射性食管炎无明显相关（r＝-0?106～0?122, P＞0?05）。将以上所有因素进行多因素分析,结果仅化疗和食管V45是≥2级放射性食管炎发生的独立危险因素（Wald＝4?626和9?882,P＜0?05）。结论局部晚期非小细胞肺癌同期放化疗明显增加放射性食管炎;DVH中物理学参数可用于预测和评价放射性食管炎的发生,其中食管V45可能是最有价值的预测指标。     

非小细胞肺癌三维适形放射治疗后急性放射性肺损伤分析

目的 探讨非小细胞肺癌(NSCLC)三维适形放射治疗后放射性肺损伤发生的相关因素,为提高NSCLC局部控制率和改善生存质量提供参考。方法 收集2000年8月至2004年12月符合入组条件接受三维适形放疗的非小细胞肺癌患者107例,其中全程三维适形放疗48例,59例前程行传统常规放疗,后程行三维适形放疗。全组患者均为根治性放疗,处方剂量60~78Gy,中位剂量66Gy。结果 全组患者放射性肺损伤发生率为62.6%,≥2级放射性肺损伤的发生率为38.3%,其中2级23例占21.5%,3级14例占13.1%,4级4例占3.7%。单因素分析显示,慢性阻塞性肺病、照射野个数、双肺接受的平均剂量、双肺V₅~V₄₀对≥2级放射性肺损伤的发生均有显著性影响,其中双肺平均剂量、双肺V₂₀、疗前伴慢性阻塞性肺病为影响放射性肺损伤发生的独立性因素。 结论 NSCLC接受三维适形放疗者,应严格限制双肺接受的平均剂量和双肺V₂₀,尤其对放疗前伴有慢性阻塞性肺病者更应高度重视避免严重放射性肺损伤的发生。     

广泛期小细胞肺癌胸部IMRT后发生放射性肺炎的危险因素分析

目的 评价广泛期小细胞肺癌(SCLC)化疗后接受胸部IMRT, 发生放射性肺炎(RP)的临床和剂量-体积因素。 方法 回顾性分析2007年至2012年接受化疗和IMRT的130例初治广泛期SCLC患者, 化疗方案以顺铂、依托泊甙方案为主, 放疗平均剂量为55.3 Gy(32~67 Gy)。RP采用常见不良反应事件评价标准(4.0版)进行评价, 分析放疗结束后2级及以上RP发生的危险因素。通过单因素和多因素统计学方法分析预测因子。 结果 全组中位随访时间37个月(4~66个月)。37例(28.5%)患者出现了≥2级的RP。单因素分析显示, 年龄和剂量学参数(双肺V5、V10、V20、V30、平均肺剂量、双肺体积)与RP显著性相关; 多因素分析显示, 只有双肺V5是≥2级RP的独立危险因素。 结论 多个临床和剂量学参数与RP的发生存在风险相关性, 尤其是双肺V5。对化疗有效的广泛期SCLC患者行胸部放疗时, 应综合考虑这些因素, 适当降低V5的体积。     

Comparison of intensity-modulated radiotherapy with three-dimensional conformal radiation therapy planning for glioblastoma multiforme

This study was designed to assess the feasibility and potential benefit of using intensity-modulated radiotherapy (IMRT) planning for patients newly diagnosed with glioblastoma multiforme (GBM). Five consecutive patients with confirmed histopathologically GBM were entered into the study. These patients were planned and treated with 3-dimensional conformal radiation therapy (3DCRT) using our standard plan of 3 noncoplanar wedged fields. They were then replanned with the IMRT method that included a simultaneous boost to the gross tumor volume (GTV). The dose distributions and dose-volume histograms (DHVs) for the planning treatment volume (PTV), GTV, and the relevant critical structures, as obtained with 3DCRT and IMRT, respectively, were compared. In both the 3DCRT and IMRT plans, 59.4 Gy was delivered to the GTV plus a margin of 2.5 cm, with doses to critical structures below the tolerance threshold. However, with the simultaneous boost in IMRT, a higher tumor dose of 70 Gy could be delivered to the GTV, while still maintaining the uninvolved brain at dose levels of the 3DCRT technique. In addition, our experience indicated that IMRT planning is less labor intensive and time consuming than 3DCRT planning. Our study shows that IMRT planning is feasible and efficient for radiotherapy of GBM. In particular, IMRT can deliver a simultaneous boost to the GTV while better sparing the normal brain and other critical structures.     

Toxicity outcome after three-dimensional conformal radiotherapy for early stage prostatic cancer

This study evaluated acute and late toxicity in patients with stages of T2a-b, N0, and M0 prostatic carcinoma treated with three-dimensional conformal radiotherapy (3D-CRT). A total of 26 patients were received a mean 69.07 Gy of 3D-CRT, and the mean follow-up time was 18.23 months. There were no statistically significant differences between the groups given < or = 70 Gy and > 70 Gy in terms of acute gastrointestinal toxicity, acute genitourinary toxicity, late gastrointestinal toxicity, and late genitourinary toxicity (p>0.05). 3D-CRT offers less normal tissue morbidity with the possibility of giving high doses of irradiation to increase local control.     

Correlation between lung fibrosis and radiation therapy dose after concurrent radiation therapy and chemotherapy for limited small cell lung cancer.

PURPOSE: To evaluate the relationship between physician-identified radiographic fibrosis, lung tissue physical density change, and radiation dose after concurrent radiation therapy and chemotherapy for limited small cell lung cancer. MATERIALS AND METHODS: Fibrosis volumes of different severity levels were delineated on computed tomography (CT) images obtained at 1-year follow-up of 21 patients with complete response to concurrent radiation therapy and chemotherapy for limited small cell lung carcinoma. Delivered treatments were reconstructed with a three-dimensional treatment planning system and geometrically registered to the follow-up CT images. Tissue physical density change and radiation dose were computed for each voxel within each fibrosis volume and within normal lung. Patient responses were grouped per radiation and chemotherapy protocol. RESULTS: A significant correlation was noted between fibrosis grade and tissue physical density change and fibrosis grade. For doses less than 30 Gy, the probability of observing fibrosis was less than 2% with conventional fractionation and less than 4% with accelerated fractionation. Physical lung density change also showed a threshold of 30-35 Gy. For doses of 30-55 Gy and cisplatin and etoposide (PE) chemotherapy, fibrosis probability was 2.0 times greater for accelerated fractionation compared with conventional fractionation (P < .005) and was correlated to increasing dose for both fractionation schedules. CONCLUSION: Lung tissue physical density changes correlated well with fibrosis incidence, and both increased with increasing dose greater than a threshold of 30-35 Gy. With concurrent PE chemotherapy, fibrosis probability was twice as great with accelerated fractionation as with once-daily fractionation.     

CT-MRI image fusion for delineation of volumes in three-dimensional conformal radiation therapy in the treatment of localized prostate cancer

The objective of this study was to assess the utility of CT-MRI image fusion software and compare both prostate volume and localization with CT and MRI studies. We evaluated the differences in clinical volumes in patients undergoing three-dimensional conformal radiation therapy for localized prostate cancer. After several tests performed to ensure the quality of image fusion software, eight patients suffering from prostate adenocarcinoma were submitted to CT and MRI studies in the treatment position within an immobilization device before the start of radiotherapy. The clinical target volume (CTV) (prostate plus seminal vesicles) was delineated on CT and MRI studies and image fusion was obtained from the superimposition of anatomical fiducial markers. A comparison of dose-volume histograms relative to CTV, rectum, bladder and femoral heads was performed for both studies. Image fusion showed a mean overestimation of CTV of 34% with CT compared with MRI. Along the anterior-posterior and superior-inferior direction, CTV was a mean 5 mm larger with CT study compared with MRI. The dose-volume histograms resulting from CT and MRI comparison showed that it is possible to spare a mean 10% of rectal volume and approximately 5% of bladder and femoral heads, respectively. This study confirmed an overestimation of CTV with CT images compared with MRI. Because this finding only allows a minimal sparing of organs at risk, considering the organ motion during each radiotherapy session and the excellent outcomes of prostate cancer treatment with CT based target identification, we are still reluctant to reduce the CTV to that identified by MRI.     

肺癌放疗患者症状性放射性肺炎预测的CT影像组学研究

目的:基于肺癌患者放疗前的CT影像组学特征,综合临床信息与放疗剂量学特征,利用机器学习方法构建症状性放射性肺炎的预测模型。方法:回顾性收集2018年11月至2020年4月在江南大学附属医院接受放疗的103例肺癌患者的临床与剂量学资料。获取这些患者放疗前胸部CT影像,勾画双侧正常肺组织结构,提取250种影像组学特征。用单...     

Volume and dose-response effects for severe symptomatic pneumonitis after fractionated irradiation of canine lung

PURPOSE: To study the dose-related incidence of severe symptomatic pneumonitis following fractionated irradiation applied to three different volumes of lung in normal beagle dogs. MATERIALS AND METHODS: A three-dimensional treatment planning system was used to design mediastinal fields of increasing width to irradiate 33%, 67% or 100% of both lungs combined in 128 normal beagle dogs. Total doses, ranging from 27 to 72 Gy, were delivered in 1.5 Gy fractions over 6 weeks. RESULTS: No dogs irradiated to 33% of their total lung volume developed severe symptomatic pneumonitis. In the 67% volume group, logistic fit of the data showed a dose-response curve with a 50% probability of developing severe symptomatic pneumonitis (ED50) after a total dose of 56.0 Gy (52.2-66.0 Gy, 95% confidence interval, CI). The more clinically relevant ED5 for the first 6 months after irradiation of 67% of the lung was 48.1 Gy (18.5-52.0 Gy, 95% CI). The ED50 and ED5 values after irradiation of the whole lung (100%) were 44.1 Gy (41.2-53.5Gy, 95% CI) and 39.1 Gy (8.8-41.8 Gy, 95% CI) respectively. CONCLUSION: Severe symptomatic pneumonitis proved to be a very informative volume-effect endpoint, clearly demonstrating that irradiated lung volume is a critical parameter to be considered in assigning thoracic radiotherapy treatment parameters. Volume effects in lung are dependent on the compensatory capacity of the nonirradiated lung. Underlying pathophysiology of irradiated tissue, as well as decreased compensatory capacity of nonirradiated tissue may have a strong effect on the dose-volume response.