Predictive factors of acute skin reactions to carbon ion radiotherapy for the treatment of malignant bone and soft tissue tumors

Background

The risk factors for radiation pneumonitis (RP) in patients with chronic obstructive pulmonary disease (COPD) are unclear. Mean lung dose (MLD) and percentage of irradiated lung volume are common predictors of RP, but the most accurate dosimetric parameter has not been established. We hypothesized that the total lung volume irradiated without emphysema would influence the onset of RP.

Methods

We retrospectively evaluated 100 patients who received radiotherapy for lung cancer. RP was graded according to the Common Terminology Criteria for Adverse Events (version 4.03). We quantified low attenuation volume (LAV) using quantitative computed tomography analysis. The association between RP and traditional dosimetric parameters including MLD, volume of the lung receiving a dose of ≥2 Gy, ≥ 5 Gy, ≥ 10 Gy, ≥ 20 Gy, and ≥30 Gy, and counterpart measurements of the lung without LAV, were analyzed by logistic regression. We compared each dosimetric parameter for RP using multiple predictive performance measures including area under the receiver operating characteristic curve (AUC) and integrated discrimination improvement (IDI).

Results

Of 100 patients, RP of Grades 1, 2, 3, 4, and 5 was diagnosed in 24, 12, 13, 1, and 1 patients, respectively. Compared with traditional dosimetric parameters, counterpart measurements without LAV improved risk prediction of symptomatic RP. The ratio of the lung without LAV receiving ≥30 Gy to the total lung volume without LAV most accurately predicted symptomatic RP (AUC, 0.894; IDI, 0.064).

Conclusion

Irradiated lung volume without LAV predicted RP more accurately than traditional dosimetric parameters.

     

肺癌同期放化治疗中放射性肺损伤的相关因素分析

 目的 观察三维适形放疗联合同期化疗治疗局部晚期非小细胞肺癌中放射性肺损伤情况,对其相关因 素进行分析,寻找合理的预测性 指标。 方法 47例符合入组条件的非小细胞肺癌患者接受三维适形放疗及同期化疗。处方剂量为60Gy常规 放疗,同期化疗方案为NP方案,对三维适形治疗计划及临床资料进行单因素、多因素分析,评 价肺损伤情况。 结果 （1）完全缓解3例, 部分缓解42例,总有效率为95.74%,1年生存率75.78%。全组发生急性放 射性肺炎0级2例,1级20 例,2级17例,3级8例,无4级放射性肺炎发生。（2）与严重放射性肺炎发生呈正相关的剂量 学因素为MLD、肺NTCP,肺V5、 V15、V20。临床资料中仅发现肿瘤GTV与严重放射性肺炎发生相关;多因素分析显示全肺平均 剂量为放射性肺炎的独立影 响因素。 结论 剂量学因素（MLD、肺NTCP,肺V5、V15、V20）可以较好地预测严重放射性肺炎的发生,全肺 平均剂量是放射性肺炎发生的独立影响因素。     

Clinical Outcomes and Safety Profile in the Treatment of Synchronous Nonmetastatic Lung Tumors With Stereotactic Body Radiation Therapy

PurposeStereotactic body radiation therapy (SBRT) has increasingly been used to treat early-stage primary lung cancers, but its effectiveness and safety in patients with multiple synchronous primary lung tumors is not as well established. Our aim was to evaluate clinical outcomes, patterns of recurrence, and toxicities for these patients.Methods and MaterialsWe queried an institutional database of patients treated with SBRT for primary lung tumors from 2007 to 2019. Patients with known metastatic disease were excluded. Recurrences were described as new primaries (NP) if they occurred as an isolated pulmonary mass outside the previous planning target volume.ResultsWe analyzed 126 lesions from 60 consecutive patients who received SBRT synchronously to ≥2 lesions for nonmetastatic lung cancers. Median total dose per lesion was 50 Gy (range, 30-60 Gy) delivered over 3 to 5 fractions. All but 4 lesions were treated to a biologically effective dose ≥100 Gy. The median follow-up time was 47.3 months (interquartile range, 34.1-65.6). Median overall survival was 46.2 months. Two and 5-year overall survival for all patients was 70% and 48%, respectively. Median progression-free survival was 26 months (interquartile range, 7.6-32.6), and at the time of data collection 25 patients (42%) had experienced any disease progression. Median time to progression was 36 months: 9 (15%) patients experienced local failure, with 1- and 2-year local failure rates of 8% and 13%, respectively. Four patients (7%) experienced regional failure, at 3, 10, 30, and 50 months. Eleven patients (18%) experienced distant failure, with 2-year distant failure rate of 13%. Thirteen patients (21%) developed NPs, with 2-year NP rate of 15.1%. Fourteen patients (23%) experienced Common Terminology Criteria for Adverse Events grade ≥2 toxicity, and 2 patients (3%) experienced Common Terminology Criteria for Adverse Events grade ≥3 toxicity (pneumonitis and hemoptysis).ConclusionsSynchronous SBRT to biologically effective dose ≥100 Gy appears safe and effective for selected patients with synchronous primary lung tumors.     

The absolute volume of PET-defined,active bone marrow spared predicts for high grade hematologic toxicity in cervical cancer patients undergoing chemoradiation

Introduction

Hematologic toxicity (HT) in cervical cancer patients can cause treatment delays and reduction in chemotherapy, especially in high risk patients. Dose to PET-defined regions of active bone marrow (ABM) has been shown to correlate with cytopenias. An absolute volume of ABM spared may accurately represent hematopoietic reserve and risk of HT. This analysis evaluates whether the volume of ABM spared can more accurately predict HT compared to conventional dosimetric parameters.

Methods

Thirty-one patients treated for cervical cancer with chemoradiation from 9/2011 to 8/2016 were retrospectively reviewed. Receiver operating characteristic (ROC) curve were used to assess optimal cutpoint criterions for grade 3+ HT based on the CTCAEv4. Conventional dosimetric parameters to PBM and ABM (mean dose, V10, V20, V40) were assessed as well as the absolute volume (cc) of PBM and ABM spared 10, 20, and 40 Gy.

Results

The absolute volume of PBM spared 10 Gy (< 230 cc; AUC 0.732, p = 0.03) as well as volume of ABM spared 10 Gy (< 179 cc; AUC 0.815, p = 0.0002), spared 20 Gy (< 186 cc; AUC 0.774, p = 0.0015), and spared 40 Gy (< 738 cc; AUC 0.887, p < 0.0001) all predicted grade 3+ HT. In patients with < 738 cc of ABM spared 40 Gy, 18/18 (100%) had grade 3+ toxicity compared to 6/13 (46%) of patients with > 738 cc of ABM spared 40 Gy (p < 0.0001).

Conclusion

The baseline volume of ABM and the fraction of ABM present in patients vary significantly. The ongoing NRG-GY006 trial and other efforts at bone marrow sparing use V10, V20, and mean dose to the ABM during planning optimization. This analysis suggests that the volume of ABM spared 40 Gy (> 738 cc) may be a stronger predictor of HT than conventional dosimetric parameters. This should be further evaluated for clinical use.

     

Radiation Pneumonitis in Breast Cancer Patients Who Received Radiotherapy Using the Partially Wide Tangent Technique after Breast Conserving Surgery

Purpose

We assessed the risk of radiation pneumonitis (RP) in terms of dosimetric parameters in breast cancer patients, who received radiotherapy using the partially wide tangent technique (PWT), following breast conservation surgery (BCS).

Methods

We analyzed the data from 100 breast cancer patients who underwent radiotherapy using PWT. The entire breast, supraclavicular lymph node, and internal mammary lymph node (IMN) were irradiated with 50.4 Gy in 28 fractions. RP was scored on a scale of 0 to 5, based on Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer toxicity criteria. The dosimetric parameters, used in analysis for the ipsilateral lung, were the mean lung dose (MLD), V₅ (percentage of lung volume that received a dose of 5 Gy or more)-V₅₀, and normal tissue complication probability (NTCP).

Results

Of the 100 patients, three suffered from symptomatic RP (symptom grade ≥2), but were relieved by supportive care. The risk of RP was not correlated with the treatment regimen. RP associated mostly with asymptomatic minimal pulmonary radiologic change or mild dry cough developed more frequently in the group with MLD ≥20.5 Gy or NTCP ≥23% than in the group with MLD <20.5 Gy and NTCP <23% (48.6% vs. 25.4%, p=0.018).

Conclusion

Dosimetric parameters of MLD and NTCP were correlated with the incidence of RP, but the clinical impact was minimal. We suggest that PWT is a safe technique for the treatment of IMN for BCS patients with low risk of symptomatic RP.     

Incidence and Risk Factors of Symptomatic Radiation Pneumonitis in Non–Small-Cell Lung Cancer Patients Treated with Concurrent Chemoradiotherapy and Consolidation Durvalumab

IntroductionData on the risk factors for symptomatic radiation pneumonitis (RP) in non–small-cell lung cancer (NSCLC) patients treated with concurrent chemoradiotherapy (CCRT) and consolidation durvalumab are limited; we aimed to investigate these risk factors.Materials and MethodsThis multicenter retrospective study, conducted at 15 institutions in Japan, included patients who were ≥20 years of age; who started definitive CCRT for NSCLC between July 1, 2018, and July 31, 2019; and who then received durvalumab. The primary endpoint was grade 2 or worse (grade 2+) RP.ResultsIn the 146 patients analyzed, the median follow-up period was 16 months. A majority of the patients had stage III disease (86%), received radiation doses of 60 to 66 Gy equivalent in 2-Gy fractions (93%) and carboplatin and paclitaxel/nab-paclitaxel (77%), and underwent elective nodal irradiation (71%) and 3-dimensional conformal radiotherapy (75%). RP grade 2 was observed in 44 patients (30%); grade 3, in four patients (3%); grade 4, in one patient (1%); and grade 5, in one patient (1%). In the multivariable analysis, lung V20 was a significant risk factor, whereas age, sex, smoking history, irradiation technique, and chemotherapy regimen were not. The 12-month grade 2+ RP incidence was 34.4% (95% confidence interval [CI], 26.7%-42.1%); the values were 50.0% (95% CI, 34.7%-63.5%) and 27.1% (95% CI, 18.8%-36.2%) in those with lung V20 ≥ 26% and < 26%, respectively (P = .007).ConclusionThe incidence of grade 2+ RP was relatively high in this multicenter real-world study, and its risk increased remarkably at elevated lung V20. Our findings can aid in RP risk prediction and the safe radiotherapy treatment planning.     

A single-nucleotide polymorphism in the methylene tetrahydrofolate reductase (MTHFR) gene is associated with risk of radiation pneumonitis in lung cancer patients treated with thoracic radiation therapy

BACKGROUND:

This study examined the association between functional single‐nucleotide polymorphisms in candidate genes from oxidative stress pathways and risk of radiation pneumonitis (RP) in patients treated with thoracic radiation therapy for locally advanced lung cancer.

METHODS:

A review was conducted of 136 patients treated with radiation therapy for lung cancer between 2001 and 2007, and who had prior genotyping of functional single‐nucleotide polymorphisms in oxidative stress genes including superoxide dismutase 2 (SOD2; rs4880) and methylene tetrahydrofolate reductase (MTHFR; rs1801131, rs1801133). RP events were retrospectively scored using the National Cancer Institute Common Terminology Criteria for Adverse Events, version 4.0. Cox proportional hazard regression was performed to identify clinical variables and genotypes associated with risk of RP of grades ≥2 and ≥3 on univariate and multivariate analysis, respectively. P values were corrected for multiple hypothesis esting.

RESULTS:

With a median follow‐up of 21.4 months, the incidence of grade ≥2 RP was 29% and grade ≥3 RP was 14%. On multivariate analysis, after adjusting for clinical factors such as concurrent chemotherapy and consolidation docetaxel, and lung dosimetric parameters such as volume receiving greater than 20 Gy and mean lung dose, MTHFR genotype (rs1801131; AA versus AC/CC) was significantly associated with risk of grade ≥2 RP (hazard ratio: 0.37; 95% confidence interval: 0.18‐0.76; P = .006, corrected P = .018) and grade ≥3 RP (hazard ratio: 0.21; 95% confidence interval: 0.06‐0.70; P = .01; corrected P = .03). SOD2 genotype was not associated with RP.

CONCLUSIONS:

This study showed an association between MTHFR genotype and risk of clinically significant RP. Further study of MTHFR‐related pathways may provide insight into the mechanisms behind RP. Cancer 2012;3654–3665. © 2011 American Cancer Society.     

非小细胞肺癌术后适形放疗肺损伤相关因素研究

目的 分析非小细胞肺癌(NSCLC)术后接受三维适形放疗(3DCRT)肺损伤的相关因素.方法 对2002年11月至2006年3月符合入组条件的90例患者进行回顾性分析,其中Ⅰ～Ⅱ期12例(切缘阳性),ⅢA期53例,ⅢB期25例.术后均接受了中位剂量60 Gy的3DCRT,38例接受了中位3周期术后化疗.观察指标为CTC 3.0 2级以上放射性肺炎(RP).应用ROC曲线分析健侧、患侧和双肺接受x Gy剂量的相对体积(Vx)和绝对体积与RP的关系.结果 全组共9例患者出现有症状的RP,RP发生率为10%.接受全肺切除的20例患者中无RP发生.RP中位发生时间在放疗开始后101 d,其中2级7例,3级2例.双肺V30、V35在RP组明显高于未发生RP组(19%∶14%,U=-2.16,P=0.030;15%:11%,U=-2.65,P=0.007).以患侧肺接受30 Gy照射的绝对体积作为分界点进行ROC曲线分析结果 显示曲线下面积为0.757,对RP预测的敏感性为88%、特异性为70%.患肺接受30 Gy照射的绝对体积>340 cm3的RP发生率明显高于体积<340 cm3的(29%∶3%,x2=9.75,P=0.003).结论 对于肺叶切除的NSCLC患者接受术后放疗,患肺接受30 Gy照射的绝对体积与RP相关.对全肺切除患者,单肺V20限制在10%以下,接受术后放疗是安全可行的.     

肺低剂量区体积预测急性放射性肺炎价值探讨

目的 观察胸部肿瘤三维适形放疗患者放射性肺炎发生情况,分析其与各临床、剂量学因素关系,探讨低剂量区体积对放射性肺炎的预测价值.方法 2005-2008年本科收治的中晚期非小细胞肺癌(NSCLC)及食管癌患者共161例接受了三维适形放疗,其中局部晚期NSCLC患者53例,处方剂量60 Gy分30～34次,均行长春瑞滨+顺铂同期化疗;食管癌患者108例,处方剂量58～70 Gy分29～35次,单纯放疗46例,余62例接受亚叶酸钙+氟尿嘧啶+顺铂同期化疗.对急性放射性肺炎进行Spearman等级相关分析、Logistic因素分析及受试者工作特征(ROC)曲线分析.结果 随访率100%.全组急性放射性肺炎总发生率为57.8%(93例),其中NSCLC组为94%(50例,4、5级各1例),食管癌组为39.8%(43例,无≥4级病例).等级相关分析结果显示患者性别(r=0.19,P=0.016)、大体肿瘤体积(r=0.52,P=0.000))、平均肺剂量(r=0.33,P=0.000)、肺正常组织并发症概率(r=0.30,P=0.000)、接受5、10、15、20、25、30 Gy照射的肺体积百分比(肺V5～V30,r=0.21～0.29,P=0.000～0.027)均与放射性肺炎发生相关.Logistic因素分析结果显示肺V5(X2=7.07,P=0.008)、大体肿瘤体积(X2=10.21,P=0.001)是预测≥2级放射性肺炎最有价值指标.ROC曲线分析结果显示曲线下面积为0.684,P=0.000;曲线界值为V5=55%.肺V5≥55%组与<55%组≥2级放射性肺炎发生率分别为43%(36/84)和18%(14/77).结论 平均肺剂量、正常组织并发症概率、V5～V30可较好预测放射性肺炎的发生,其中V5可能是最有价值的预测性指标.当V5>55%时≥2级的急性放射性肺炎的发生率可能会明显增加,制定治疗计划时除平均肺剂量、V20、V30外,还应将低剂量区体积限制在适当范围内.     

Clinical and Dosimetric Predictors of Radiation Pneumonitis in Patients With Non-Small Cell Lung Cancer Undergoing Postoperative Radiation Therapy

PurposeRadiation pneumonitis (RP) is a common and potentially life-threatening toxicity from lung cancer radiation therapy. Data sets reporting RP rates after postoperative radiation therapy (PORT) have historically been small and with predominantly outdated field designs and radiation techniques. We examined a large cohort of patients in this context to assess the incidence and causes of RP in the modern era.Methods and MaterialsWe reviewed 285 patients with non-small cell lung cancer treated with PORT at our institution from May 2004 to January 2017. Complete dosimetric data and clinical records were reviewed and analyzed with grade 2 or higher RP as the endpoint (RP2+) (Common Terminology Criteria for Adverse Events v4.0). Patients were a median of 67 years old (range, 28-87), and most had pathologic stage III non-small cell lung cancer (91%) and received trimodality therapy (90%). Systematic dosimetric analyses using Dx increments of 5% and Vx increments of 2 Gy were performed to robustly evaluate dosimetric variables. Lung V₅ was also evaluated.ResultsThe incidence of RP2+ after PORT was 12.6%. Dosimetric factors most associated with RP2+ were total lungV₄ (hazard ratio [HR] 1.04, P < .001) and heart V₁₆ (HR 1.03, P = .001). On univariate analysis, the clinical factors of age (HR 1.05, P = .006) and carboplatin chemotherapy (HR 2.32, P = .012) were correlated with RP2+. On step-up multivariate analysis, only bivariate models remained significant, including lungV₅ (HR 1.037, P < .001) and age (HR 1.052, P = .011).ConclusionsThe incidence of RP after PORT is consistent with the literature. Factors correlated with RP include lung and heart doses, age, and carboplatin chemotherapy. These data also suggest that elderly patients may be more susceptible to lower doses of radiation to the lung. Based on these data, dose constraints to limit the risk of RP2+ to <5% in the setting of PORT include lungV₅ ≤65% in patients <65 years old and lungV₅ ≤36% in patients 65 years or older.     

Effect of Tumor Location and Dosimetric Predictors for Chest Wall Toxicity in Single-Fraction Stereotactic Body Radiation Therapy for Stage I Non-Small Cell Lung Cancer

Purpose

Dosimetric parameters to limit chest wall toxicity (CWT) are not well defined in single-fraction (SF) stereotactic body radiation therapy (SBRT) phase 2 trials. We sought to determine the relationship of tumor location and dosimetric parameters with CWT for SF-SBRT.

Symptomatic Radiation Pneumonitis in Elderly Patients Receiving Thoracic Irradiation

PurposeAdvanced age has been associated with increased risk of radiation pneumonitis. The purpose of this study was to examine the clinical and dosimetric predictors of radiation pneumonitis in elderly patients relative to younger patients treated with thoracic radiation therapy for lung cancer.MethodsTwo hundred fifty-six consecutive patients with stage I-III small cell and non–small-cell lung cancer treated with definitive radiation with or without concurrent chemotherapy, between 2004 and 2009, were reviewed. Pneumonitis was graded by using the Common Terminology Criteria for Adverse Events version 4. Clinical parameters and dosimetric variables were assessed in univariate and multivariate analysis to evaluate predictors of grade ≥2 pneumonitis in patients age ≥70 years and age <70 years.ResultsThere were 99 patients age ≥70 and 157 patients age <70 years old. Pneumonitis occurred in 32 patients (grade 2 [22], grade 3 [7], grade 4 [3], grade 5 [1]). On multivariate analysis, the V₅ Gy (P = .005) and age ≥70 years (P = .001) predicted for grade ≥2 pneumonitis, whereas angiotensin converting enzyme inhibitor use was associated with decreased risk (P = .02). Pneumonitis grade ≥3 occurred in 10% (n = 10/99) of patients age ≥70 years and in 1% (n = 1/157) of patients <70 years (P = .001). In patients with a V₂₀ Gy >31%, the incidence of grade ≥3 pneumonitis was 33% (n = 4/12) in elderly patients compared with 2% (n = 1/44) in younger patients (P = .005).ConclusionsElderly patients were observed to have an increased risk of symptomatic pneumonitis. Radiation dose parameters remain useful in this population; however, the threshold for clinically acceptable pneumonitis may be lower than in younger patients. angiotensin converting enzyme inhibitors use may mitigate radiation pneumonitis.     

Dosimetric and Clinical Predictors for Acute and Late Gastrointestinal Toxicity Following Chemoradiotherapy of Locally Advanced Anal Cancer

AimsTo analyse dosimetric and clinical predictors for acute and late gastrointestinal toxicity following chemoradiotherapy of anal cancer.Materials and methodsConsecutive patients with locally advanced (T2 ≥4 cm – T4 or N+) anal cancer were selected from an institutional database (n = 114). All received intensity-modulated radiotherapy with concomitant 5-fluorouracil and mitomycin C. Gastrointestinal toxicity was retrospectively graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 5.0 and bowel cavity, small bowel and large bowel were contoured. Dosimetric and clinical variables were tested for associations with acute grade ≥3 gastrointestinal toxicity and late grade ≥2 gastrointestinal toxicity using the Mann–Whitney test, area under receiver operating characteristic curve (AUC) and logistic regression.ResultsThe median follow-up was 40 months. Acute grade ≥3 gastrointestinal toxicity was seen in 51 (44.7%) of the patients; late grade ≥2 gastrointestinal toxicity was seen in 36 of the patients (39.6% of 91 patients with >1 year recurrence-free follow-up). Bowel cavity V30Gy was the best dosimetric predictor for acute gastrointestinal toxicity (AUC 0.633; P = 0.02). Large bowel V20Gy was the best dosimetric predictor for late gastrointestinal toxicity (AUC 0.698; P = 0.001) but showed no association with acute gastrointestinal toxicity. In multivariate logistic regression, increasing age was significantly associated with acute gastrointestinal toxicity; smoking and large bowel V20Gy were significantly associated with late gastrointestinal toxicity. Patients who experienced acute grade ≥3 gastrointestinal toxicity were not at an increased risk of late grade ≥2 gastrointestinal toxicity (odds ratio 1.3; P = 0.55).ConclusionsFactors of importance for acute and late gastrointestinal toxicity were not the same. Bowel cavity V30Gy is a good metric to use for the prediction of acute gastrointestinal toxicity, but the results of our study indicate that individual large and small bowel loops need to be contoured for better prediction of late gastrointestinal toxicity. The role of the large bowel as an important organ at risk for late gastrointestinal toxicity merits further research.     

FDG PET-CT标准摄取值在预测放射性肺炎发生中的作用

目的 探讨肺癌患者放射治疗前后FDG PET-CT标准摄取值(SUV)及其变化在预测放射性肺炎发生中的作用.方法 40例未经手术的非小细胞肺癌(NSCLC)患者在放射治疗前后均行PET-CT检查,分别测量出受照≤5 Gy、5.1～15 Gy、15.1～35 Gy、35.1～60 Gy以及>60 Gy肺组织放射治疗前后的平均SUV,比较发生放射性肺炎组与未发生放射性肺炎组SUV的变化情况,以及受照肺组织的SUV与未受照射肺组织SUV值之比(L/B).结果 40例患者中,有8例在治疗后发生放射性肺炎,其中2级6例,3级2例.受照剂量35.1～60 Gy肺组织的SUV与放射性肺炎的发生明显相关,当SUV≥1时,放射性肺炎的发生率为41.7%,明显高于全组放射性肺炎的发生率(20.0%;X2=3.96,P<0.05),SUV预测放射性肺炎的敏感度和特异度分别为62.5%和78.1%.L/B≥2.5时,放射性肺炎的发生率为40.7%,亦明显高于全组放射性肺炎的发生率(20.0%;X2=4.92,P<0.05).以L/B≥2.5为标准预测放射性肺炎的敏感度和特异度分别为72.7%和90.9%.SUV≥1与L/B≥2.5在预测放射性肺炎发生率之间的差异无统计学意义(X2=0.002,P>0.05).结论 SUV和L/B的大小与放射性肺炎的发生呈正相关,临床医生可根据FDG PET-CT提供的SUV和L/B来预测放射性肺炎的发生.     

肺癌与食管癌螺旋断层放疗致放射性肺炎的临床观察

目的 探讨螺旋断层放疗（HT）治疗肺癌与食管癌致放射性肺炎的发生情况及与双肺剂量体积（DVH）和临床病理特征的关系。方法 回顾性分析HT 治疗的19例肺癌和14食管癌患者的临床资料。全组患者中13例仅行HT治疗,20例联合化疗。放疗剂量：小细胞肺癌54～61.8Gy／27～28次,非小细胞肺癌54～66Gy／25～31次,食管癌60～66Gy／28～30次。结果 全组33例患者中,发生0级放射性肺炎8例（24.2％）,1级15例（45.4％）,2级1例（3.0％）,3级5例（15.2％）,5级4例（12.1％）。DVH参数分析显示,发生≥2级放射性肺炎与V30～V45有关,与V5～V25、双肺平均剂量（MLD）、计划靶区（PTV）无关。临床病理特征中,发生≥2级放射性肺炎与ECOG评分有关,与病种、性别、年龄、吸烟、慢性阻塞性肺病和化疗情况无关。结论 HT治疗肺癌与食管癌未明显增加放射性肺炎的发生率,一般状态差、分期晚的患者应严格限制DVH。     

Evaluation of the Radiation Pneumonia Development Risk in Lung Cancer Cases

Background: Concurrent chemo-radiotherapy is the recommended standard treatment modality for patients with locally advanced lung cancer. The purpose of three-dimensional conformal radiotherapy (3DCRT) is to minimize normal tissue damage while a high dose can be delivered to the tumor. The most common dose limiting side effect of thoracic RT is radiation pneumonia (RP). In this study we evaluated the relationship between dose-volume histogram parameters and radiation pneumonitis. This study targeted prediction of the possible development of RP and evaluation of the relationship between dose-volume histogram (DVH) parameters and RP in patients undergoing 3DCRT. Materials and Methods: DVHs of 41 lung cancer patients treated with 3DCRT were evaluated with respect to the development of grade ≥ 2 RP by excluding gross tumor volume (GTV) and planned target volume (PTV) from total (TL) and ipsilateral (IPSI) lung volume. Results: Were admitted statistically significant for p<0.05. Conclusions: The cut-off values for V5, V13, V20, V30, V45 and the mean dose of TL-GTV; and V13, V20,V30 and the mean dose of TL-PTV were statistically significant for the development of Grade ≥2 RP. No statistically significant results related to the development of Grade ≥2 RP were observed for the ipsilateral lung and the evaluation of PTV volume. A controlled and careful evaluation of the dose-volumehistograms is important to assess Grade ≥2 RP development of the lung cancer patients treated with concurrent chemo-radiotherapy. In the light of the obtained data it can be said that RP development may be avoided by the proper analysis of the dose volume histograms and the application of optimal treatment plans.     

Heart Dose Is an Independent Dosimetric Predictor of Overall Survival in Locally Advanced Non–Small Cell Lung Cancer

IntroductionIn the randomized trial of standard- versus high-dose chemoradiotherapy for locally advanced (LA) NSCLC (Radiation Therapy Oncology Group 0617), overall survival (OS) was worse in the high-dose arm. Although heart dose was suggested as a contributing factor, actionable parameters have not been established. We present an analysis of clinical and dosimetric parameters affecting OS in this patient population, focusing on heart dose.MethodsClinical data were collected on 416 patients with LA NSCLC treated at a single institution, with a subset of 333 available treatment plans recontoured using Radiation Therapy Oncology Group 0617 normal tissue guidelines. Toxicity and dosimetry data were analyzed for 322 patients; multivariate analysis was performed on 251 patients. Dosimetric parameters of radiation to tumor and organs at risk were analyzed with clinical data pertaining to OS, disease-free survival, and toxicity.ResultsPatients were treated with radiation therapy to prescribed doses of 50.0 to 84.9 Gy (median 66.0 Gy). Median follow-up was 14.5 months. Median OS was 16.8 months. The 1- and 2-year OS rates were 61.4% and 38.8%, respectively. On multivariate analysis, factors independently associated with worse OS were increasing heart V₅₀ (volume receiving ≥50 Gy), heart volume, lung V₅ (proportion of the lung structure [excluding the target volume]) receiving at least 5 Gy), bilateral mediastinal lymph node involvement, and lack of concurrent chemotherapy. When stratified by heart V₅₀ less than 25% versus 25% or greater, the 1-year OS rates were 70.2% versus 46.8% and the 2-year OS rates were 45.9% versus 26.7% (p < 0.0001). Median heart V₅₀ was significantly higher (20.8% versus 13.9%, p < 0.0001) for patients with cardiac toxicity with a Common Terminology Criteria for Adverse Events grade of 1 or higher.ConclusionsHeart dose is associated with OS and cardiac toxicity for patients with LA NSCLC treated with chemoradiotherapy.     

Comparison of risk and predictors for early radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with radiotherapy with or without surgery

ObjectivesTo investigate risk and predictors for radiation pneumonitis (RP) and tolerance of lung to radiation in patients treated with thoracic radiotherapy (RT) with or without surgery.Methods and materialsA total of 433 consecutive patients with locally advanced non-small cell lung cancer were followed after three-dimensional conformal radiotherapy. Among them 284 received RT without surgical intervention and 149 received postoperative radiotherapy (PORT). RP was graded according to Common Terminology Criteria for Adverse Events version 4.0.ResultsThe rate of grade ≥2 and grade ≥3 RP was 50 and 16% in the PORT group compared with 38 and 9% in the non-surgical group (p < 0.05 for each comparison). The lung volume was significantly smaller in PORT group than in no-surgical group (3181 ± 915 cm³ vs. 4010 ± 1120 cm³, p < 0.05). Age, chemotherapy, mean lung dose (MLD) and planning target volume (PTV) were predictors of RP for both non-surgical group and PORT group. Mean heart dose (MHD) predicted RP in PORT group only (OR = 1.28, p = 0.003). Among patients who developed RP, V20, MLD, and MHD were significantly lower in PORT group than in no-surgical group (p < 0.05 for each comparison).ConclusionsExcept MHD predicting RP in PORT group only, most of predictors for RP were consistent in patients treated with RT with or without surgery. Patients receiving PORT had a higher risk of RP than patients receiving RT without surgery did, possibly due to decreased lung volume and lower tolerance of lung to chemoradiotherapy.     

Clinical Outcomes and Predictors of Lung Toxicity After Multiple Courses of Lung Stereotactic Body Radiotherapy for Early-Stage Non–Small Cell Lung Cancer

BackgroundThe clinical outcomes of multicourse lung stereotactic body radiotherapy (SBRT) have yet to be validated in a prospective study, and there are a lack of data on allowable composite dosimetry.Patients and MethodsForty-four patients underwent multicourse lung SBRT for recurrent or metachronous NSCLC. The median biologically effective dose (BED₁₀) for the first course and subsequent courses were 132 and 100 Gy, respectively. Patient and treatment characteristics were evaluated to determine the correlation with the development of radiation pneumonitis (RP).ResultsThe local control rate was 91%. A total of 13.6% developed a grade 2+ RP, and 4.5% developed a grade 3+ RP, including one grade 5. On univariable analysis, multiple composite dosimetric factors (V₅ [proportion of lung structure receiving at least 5 Gy], V₁₀, V₂₀, V₄₀, and mean lung dose) were correlated with the development of RP. When comprised of the first and second course of SBRT, a composite lung V₅ of < 30% and > 50% was associated with a 0 and 75% incidence of grade 2+ RP, respectively. We identified no significant correlation on multivariable analysis but observed a strong trend between composite lung V₅ and the development of grade 2+ RP (hazard ratio, 1.157; P = .058). Evaluation of multiple clinical factors also identified a significant correlation between the timing of repeat lung SBRT and the development of grade 2+ RP after the second course (P = .0028).ConclusionSubsequent courses of lung SBRT, prescribed to a median BED₁₀ of 100 Gy, can provide a high rate of local control with a 4.5% incidence of grade 3+ toxicity. Composite lung V₅ and the timing of the second course of lung SBRT may be correlated to the development of RP.