Acute Radiation Pneumonitis Research Articles

Severe acute radiation pneumonitis after concurrent chemoradiotherapy in non-small cell lung cancer

Objective The study is to investigate the predictive values of dosimetric parameters and patient related factors in severe acute radiation pneumonitis (SARP) after concurrent chemoradiotherapy in non-small cell lung cancer (NSCLC).Methods In all,147 NSCLC patients treated with concurrent chemotherapy and 3DCRT between 2006 and 2010 was collected.Independent sample t test was used to compare parameter values between patients with SARP and those without SARP.Logistic regression was used to identify significant determined factor.Predictive value of each parameter was tested by ROC analysis.Pearson correlation was used to analyze correlations between parameters.Represent factors were identified by factor analysis.Results The incidence of SARP was 9.5％ ( 14/147 ).The means lung dose (MLD),V20,V30,V40,and V50 ( x2 =4.87 -6.84,P =0.009 -0.025,respectively ) were determining factors for SARP.Our datasets shows that for SARP ＜5％,MLD,V20,V30,V40 and V50 should be ≤16.77 Gy,V20≤34.15％,.V30 ≤23.62％,.V40 ≤ 18.57％,V50 ≤ 13.02％.ROC analysis show that areas under MLD,V20,V30,V40 and V50 curves was corresponding to 0.678,0.661,0.667,0.677,and 0.651,respectively.In addition,the sensitivity and specificity of each parameter at cutoff values are:78.0％ and 48.1％ for MLD;42.9％ and 82.0％ for V2o ;78.6％ and 52.9％ for V30 ;71.4％ and 61.7％ for V40,and 57.1％ and 67.7％ for V50.Factor analysis suggest that we can choose 1 or 2 parameters from MLD,V20,or V30,and another from V40 or V50 for predicting.The incidence of SARP was greater in patients with tumorsin right lower lung than other locations ( 22.2％ vs 6.7％,x2 =6.19,P =0.0 2 3 ).Conclusions The MLD,V20,V30,V40 and V50 are determining factors for SARP.As predictive value of each parameter alone is relatively week,using two or more parameters to predict SARP is recommended. Key words: Lung neoplasms/radiotherapy; Radiotherapy,three-dimensional conformal; Radiation pneumonitis; Dose volume histogram

Cancers bronchiques non à petites cellules : facteurs prédictifs de survenue de pneumopathie radique

PurposeTo evaluate the predictors of acute radiation pneumonitis after conformal thoracic radiotherapy in the treatment of locally advanced non-small cell lung cancer. Patients and methodsForty-seven consecutive patients were treated with conformal thoracic irradiation for locally advanced non-small cell lung cancer and retrospectively analysed. The mean total dose of radiotherapy was 65Gy with respiratory gating in 19 cases. Neoadjuvant and concomitant chemotherapy was performed in 33 patients (70%) and 41 patients (87%) respectively. ResultsEleven patients (23%) had an acute radiation pneumonitis, resulting in death for one patient. In univariate analysis, age, sex, pretherapeutic value of forced expiratory volume, non-gated radiotherapy and type of concomitant chemotherapy did not appear as contributing factors in contrast to the administration of neoadjuvant gemcitabine (P=0.03). The occurrence of acute radiation pneumonitis was significantly associated with non-tumour lung volumes irradiated to 13Gy (V13, P=0.04), 20Gy (V20, P=0.02) and 25Gy (V25, P=0.006), the mean lung dose (P=0.008) and lung normal tissue complication probability (P=0.004). In multivariate logistic regression analysis, the occurrence of acute radiation pneumonitis was significantly associated with age above 75 years (odds ratio [OR]=16.72 ; P=0.02) and with administration of neoadjuvant gemcitabine (OR=18.08, P=0.04). ConclusionAcute radiation pneumonitis is a common acute side effect of the conformal thoracic radiotherapy of locally advanced non-small cell lung cancer, requiring close post-treatment follow-up, particularly for elderly patients. The use of gemcitabine before radiation should be avoided. The benefits and risks of conformal thoracic radiotherapy must be carefully analyzed in view of the dosimetric parameters obtained.

Clinical analysis of three-dimensional conformal radiotherapy plus chemotherapy for locally advanced non-small cell lung cancer:study of 56 patients

Objective To analyze the efficacy,complications and prognostic factors of three-dimensional conformal radiotherapy(3 DCRT)for locally advanced non-small cell lung cancer(NSCLC).Methods 56 patients who were treated either by radiotherapy alone(14 patients)or radiotherapy plus chemotherapy(42 patients)from Jan.2005 to Feb.2008 were enrolled.The patient cohort consisted of 36 men and 20 women,median age 62,median total dose 60 Gy.Results The following-up rate was 96%.The number of patients completed follow-up were 14 and 10,respectively at 3-year and 5-year.The response rate of 3DCRT was 70%.with complete mmission 9%and partial remission 61%.The 1-、3-、and 5-.year survival rates were 62%、25% and 17%,respectively,and the median survival time(MST)was 20 months.By logrank test,clinical stage,KPS perfomance,tumor volume,radiation dose,treatment regimen and response to treatment showed statistically dramatic impact on overall survival.By Cox muhivariable regression,the independent adverse prognostic factors by both univariate analysis and multivariate analysis were clinical stage,treatment type,and response to treatment.Grade 2 acute radiation pneumonitis was observed in 1 patient and grade 3 in 1 patient.Late grade 2 lung injury developed in 1 patient,and grade 3 in 1 patient.Acute grade 1 radiation esophagitis were observed in 20 patients.and above Grade 2 in 5patients.Acute grade 1+2 hematologic toxicity developed in 15 patients,and above Grade 2 developed in 4 patients.Conclusions 3 DCRT was feasible in the treatment of locally advanced NSCLC with acceptable normal tissue toxicity.Relative early stage.radio-chemotherapy with total radiation dosage≥60 Gy and good immediate tumor response are favorable prognostic factors for overall survival. Key words: Cancer,non-small cell lung/radiochemotherapy; Radiotherapy,three dimensional conformal; Chemotherapy,sequential; Chemotherapy,concurrent; Prognosis

Stereotactic body radiaton therapy for 15 patients with small lung neoplasms

背景与目的立体定向放疗在临床应用中取得了令人振奋的成果。本研究旨在评价直线加速器大分割立体定向放疗治疗肺部小肿瘤的可行性。方法纳入2005年9月-2009年8月本院收治的15例符合要求的非小细胞肺癌（non-small cell lung cancer, NSCLC）及肺部转移瘤患者。放疗前在模拟机下测定肺部病灶的左右、前后、头尾三个方向的呼吸运动幅度，采用CT模拟定位，选择三维适形立体定向放疗。放疗剂量如下：5 Gy×10次/12天生物有效剂量[（biological effective dose, BED）=75 Gy]2例，6 Gy×8次/10天（BED=76.8 Gy）3例，8 Gy×6次/8天（BED=86.4 Gy）2例，12 Gy×4次/4天（BED=132 Gy）8例，病变直径1.5 cm-4 cm，毒性评价标准按照NCI-CTCAE 3.0版本进行。结果15例患者患者近期疗效完全缓解（complete response, CR）率为60%，部分缓解（partial response, PR）率为20%，总有效率（CR+PR）为80%。1年局部控制率为100%，1年生存率为86.67%。肺的早期放射性反应0级2例，Ⅰ级9例，Ⅱ级4例，无Ⅲ级以上的副反应。结论利用直线加速器对肺部小病灶实施48 Gy/4次/4天的照射是可行的。

SIDE-EFFECTS OF HEAD AND NECK CANCER TREATMENT AND POTENTIAL STRATEGIES TO REDUCE THEM

not received. TARGETING ANGIOGENESIS OR VASCULOGENESIS IN CANCER THERAPY: ADVANTAGES AND POTENTIAL RISKS M. Brown, G. O. Ann, M. Kioi l , J. Williams 2 1 STANFORD UNIVERSITY SCHOOL OF MEDICINE, Department of Radiation Oncology, Stanford, USA 2 UNIVERSITY OF ROCHESTER CANCER CENTER, Department of Radiation Oncology, Rochester NY, USA Purpose/Objective: The objective of this talk is to discuss the concept that damage to blood vessels can be repaired by circulating proangiogenic cells (a process known as vasculogenesis) and that the response of tumors to irradiation can be increased by blocking angiogenesis. However, does this also increase the radiation damage to normal tissues? Material/Methods; We have tested the hypothesis that the radiation response of tumors can be increased by blocking vasculogenesis using two human tumors (FaDu and U251 glioma) transplanted into nude mice. We have also examined the response of normal skin and radiation-induced pneumonitis in mice. We have used a variety of bone marrow transplantation studies to identify bone marrow derived cells in tumors. Results: We show that an essential contributor to vasculogenesis in irradiated tumors are CD11b+ myelomonocytic cells expressing MMP-9, and circulating endothelial cells (ECs) or endothelial progenitor cells (EPCs). These are recruited to the irradiated tumors by stromal derived factor 1 (SDF-1) induced by increased levels of HIF-1 in the irradiated tumors. Importantly, a variety of ways of blocking this process (neutralizing antibodies to CD11b, inhibition of the interaction of SDF-1 with CXCR4 and with CXCR7, antibodies against CXCR4, and inhibition of HIF-1) render tumors less able to recur following irradiation. Thus, this is an important strategy for improving the cure rate of solid tumors by radiation. However, the exogenous transplantation of proangiogenic cells, including EPCs, has become an important strategy for accelerating the repair of normal tissue injury by vascular damage (such as in myocardial infarcts), so it is possible that inhibiting their accumulation in irradiated tissues might increase normal tissue damage by irradiation. We have tested this in two systems: acute skin reactions and radiation pneumonitis in mice. In neither case did the administration of neutralizing antibodies against CD11b+ monocytes following irradiation increase the radiation-induced injury. In fact in the case of the skin reactions we found a significant protection. We will discuss the evidence that inhibition of EPCs might increase normal tissue injury following irradiation. Conclusion: Blocking vasculogenesis can have a major positive impact on the response of solid tumors to irradiation. Much work remains to be done to determine if this is safe for normal tissues, but the initial evidence is that this strategy of blocking vasculogenesis does not increase radiation damage to normal tissues.

The predictive value of basic lung function and dosimetric parameters of acute radiation pneumonitis during the treatment of concurrent chemoradiotherapy

Objective To observe the incidence of RP in NSCLC and esophageal carcinoma treated with 3DCRT and investigate the relationship between acute RP and lung function and dosimetric parameters.Methods From October 2006 to August 2008, 3DCRT plus concurrent chemotherapy of NP or LFP were applied to 64 patients with locally advanced NSCLC or esophageal carcinoma. twenty-three patients suffered form NSCLC and 41 patients from esophageal carcinoma, the prescription doses were 60 Gy/30fx and 58 -64 Gy/29 -32fx, respectively. Results For patients with esophageal carcinoma, 34% developed RP(9 grade 1,3 grade 2 and 2 grade 3). For patients with NSCLC, 96% developed RP(9 grade 1, 8 grade 2 and 5 grade 3). There was significant difference between the two groups(t =5. 55,P=0. 000). The FEV1.0/FVC and DLCO of patients with NSCLC were significantly lower than those of esophageal carcinoma, the ratio were 75.6%:82.7%(t=2.75,P=0.008)and 71.7%:81.0%(t=2.50, P=0.015),respectively. For patients whose FEV1.0, FEV1.0/FVC%, DLCO ＜80% and ≥80% before irradiation,the incidence of ≥2grade ARP were 35% vs 25% ,31% vs 26% and 35% vs 19%, respectively(x2 = 1.81,0.15,2. 13,P =0.179,0.697,0.144). While for patients whose FEV1.0 ＜ 70% and ≥70%, the incidence of severe ARP were 67% and 22% ,respectively(x2 =5.64, P =0.018). Spearman correlated analysis indicated that all the dosimetric parameters had relation with ≥ 2 grade ARP . The V20 of lung and MLD were found independently associated with RP according to multivariate analysis(x2 = 4.61,6.97, P = 0.032,0.008).Conclusions Parameters of basic lung function can predict the incidence of ≥2 grade RP to some extent,especially when the value of FEV1.0, FEV1.0/FVC%, and DLCO was lower. However, the V20 of lung and MLD may be the most valuable predictors. Key words: Lung neoplasms/radiotherapy; Esophagus neoplasms/radiotherapy; Radiotherapy,three-dimensional conformal; Radiation pneumonitis; Lung function

The Development of Classically and Alternatively Activated Macrophages Has Different Effects on The Varied Stages of Radiation-induced Pulmonary Injury in Mice

The classical and alternative activation of macrophages has been proposed to play a role in radiation-induced pneumonitis and fibrosis, respectively. To test this hypothesis, the thoraces of C57BL/6 mice were irradiated with 12 Gy X-rays, and irradiated and control mice were euthanized at 1, 8, 12, 24 and 72 hours, and 2, 4, 8, 16 and 24 weeks after irradiation. The expression of inducible nitric oxide synthase (iNOS) and arginase type 1 (Arg-1) was evaluated at the mRNA and protein levels at different stages post-irradiation. We demonstrated that the enhanced mRNA and protein expression of iNOS occurred within the pneumonic stage, whereas the high levels of Arg-1 expression occurred within the fibrotic phase. Immunohistochemistry revealed that iNOS and Arg-1 were mainly expressed in macrophages. The expression of iNOS and Arg-1 may be associated with acute radiation pneumonitis and the development of radiation fibrosis, respectively. Although the function of macrophages cannot explain the whole process of radiation-induced pulmonary injury development, it may play an important regulatory role during this process.

Abstract P4-11-05: Acute and Late Toxicity Results from the SECRAB Trial: The Optimal SEquencing of Adjuvant Chemotherapy (CT) and RAdiotherapy (RT) in Early Breast Cancer (EBC)

Abstract Background: SECRAB is a large multicentre randomised controlled trial designed to determine the optimal sequence of CT and RT for women with EBC. The second objective of this trial was to determine if CT and RT treatment modalities could be given together without increased toxicity or compromising either modality. See abstract no 851519 for details of CT and RT scheduling. Methods: Data on acute skin reaction was collected on completion of RT and graded as mild, moderate or severe. Late toxicity data was collected annually and included lymphoedema, telangiectasia, severe subcutaneous fibrosis, brachial plexopathy, rib fracture, ischaemic heart disease, symptomatic lung fibrosis, and clinical radiation pneumonitis. Results: Between Jul 98 and Mar 04, 2296 women were randomised. Acute toxicity data was collected on 2267 patients who received RT. The distribution of RT schedules was balanced across treatment arms, with the majority of patients (67%) receiving 40Gy/15F (15F). Significantly more patients in the Syn arm experienced a delay of >10 days in CT delivery (11% vs 5%, p < 0.0001). Very few patients experienced a >7 days delay in RT in either arm (Syn n=12 vs Seq n=3). In a sub-set of 880 patients dose intensity of CT was not significantly different between the two arms. Percentage skin toxicities for the Syn and Seq arms respectively were: None 22.9 vs 36.3; Mild 52.4 vs 48.1; Moderate 20.2 vs 13.6; Severe 3.8 vs 1.1. A significantly (p < 0.001) higher proportion of patients on the Syn arm suffered a moderate or severe skin reaction compared to those on the Seq arm. An unplanned exploratory analysis by duration of RT showed that patients receiving >15F (45Gy/20F or 50Gy/25F) had a significantly worse acute skin reaction than those receiving 15F (25% vs 16%, p=<0.001). 5 patients on the Syn arm were admitted to hospital as a result of a severe RT reaction, 3 received >15F. Acute radiation pneumonitis was 0.3% in both arms (n=5 in total). Percentage late toxicities for the Syn and Seq arms respectively were not significantly different for: moderate/severe lymphoedema 6.1 (n=70) vs 5.5 (n=64); severe subcutaneous fibrosis 1.3 (n= 15) vs 0.6 (n=7); brachial plexopathy 0.2 (n=2) vs 0.1 (n=1); rib fracture 0.6 (n=7) vs 0.4 (n=5); ischaemic heart disease 0.4 (n=5) vs 0.4 (n=2); symptomatic lung fibrosis 0.3 (n=15) vs 0.3 (n=7); and late clinical radiation pneumonitis 0.1 (n=1) vs 0.1 (n=1). Howevermoderate/severe telangiectasia was 2.5% vs 1.3% in the Syn and Seq arms respectively (p =0.05). This difference was not seen in patients receiving 15F. Conclusions: The delivery of Syn CT-RT in the adjuvant treatment of EBC is associated with an increase in acute skin toxicity however the percentage of severe reactions is less than 5%. These skin reactions were seen predominantly in patients treated with concurrent RT (>15F). An increase in late skin telangiectasia was also seen in patients receiving >15F. There was no difference in other late toxicities recorded. Syn CT-RT is feasible in the adjuvant treatment of EBC and does not result in a reduction in dose intensity of delivered CT. The optimal schedule is 40Gy/15F which is now the standard regime used in the UK. Citation Information: Cancer Res 2010;70(24 Suppl):Abstract nr P4-11-05.

Treatment of large stage I–II lung tumors using stereotactic body radiotherapy (SBRT): Planning considerations and early toxicity

Purpose To study the dosimetric predictors of early clinical toxicity following SBRT in patients with lung tumors and planning target volumes (PTV) exceeding 80 cm 3. Methods Eighteen consecutive patients who were treated using volumetric modulated arc therapy (RapidArc™) were assessed. All were either unfit or refused to undergo surgery or chemoradiotherapy. PTV planning objectives were as used in the ROSEL study protocol. Clinical toxicity was scored using Common Toxicity Criteria AE4.0. Lung volumes receiving 5, 10, 15, and 20 Gy ( V 5, V 10, V 15 and V 20) and mean lung dose were assessed and correlated to symptomatic radiation pneumonitis (RP). Results Median age, age-adjusted Charlson-comorbidity score and PTV size were 74, 7.5 and 137 cm 3, respectively. At a median follow-up of 12.8 months, 8 deaths were recorded: 5 arising from comorbidity, 2 were potentially treatment-related and 1 had local recurrence. RP was reported in 5 patients (grade 2 in 3 and grade 3 in 2). All RP occurred in plans without a high priority optimization objective on contralateral lung. Acute RP was best predicted by contralateral lung V 5 ( p < 0.0001). Conclusion After SBRT using RapidArc in lung tumors >80 cm 3, the contralateral lung V 5 best predicts RP. Limiting contralateral lung V 5 to <26% may reduce acute toxicity.

The Predictive Value of Basic Lung Function and Dosimetric Parameters to Acute Radiation Pneumonitis (ARP) during the Treatment of Concurrent Chemoradiotherapy

Results: (1) For patients with esophageal carcinoma, 34.1% developed RP (9 grade 1, 3 grade 2 and 2 grade 3). For patients with NSCLC, 95.7% developed RP (9 grade 1, 8 grade 2 and 5 grade 3). There was no significant difference of FVC (forced vital capacity) and FEV1.0 (forced expiratory volume in 1s) between esophageal carcinoma and NSCLC patients, but the DLCO (diffusion capacity of carbon monoxide) of NSCLC was significantly lower than that of esophageal carcinoma. (2) The volume of GTV, FEV1.0, DLCO and all dosimetric parameters (MLD, NTCP, and V5-30) could predict RP according to univariate analysis. For patients whose FVC\80% and $80%, DLCO #80% and .80%, FEV1.0\70% and $70% before irradiation, the incidence of $2 grade RP was 38.1%vs23.3%, 35.1%vs18.5% and 66.7%vs21.8%, respectively. For patients whose chemotherapy cycles #2 and.2, the incidence of severe RP was 14.3% and 38.9%, respectively.(3)The volume of GTV, cycles of chemotherapy, MLD and V20 were found independently associated with RP according to multivariate analysis.

The Predictive Value of Low Dose Volume of Lung to Acute Radiation Pneumonitis in Thoracic Carcinoma Treatment using Three Dimensional Conformal Radiotherapy

The Predictive Value of Low Dose Volume of Lung to Acute Radiation Pneumonitis in Thoracic Carcinoma Treatment using Three Dimensional Conformal Radiotherapy

Low dose volume of the lung in prediction of acute radiation pneumonitis

Objective To observe the incidence of radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) or esophageal carcinoma treated by three-dimensional conformal radiation therapy (3DCRT), and investigate the predictive value of low dose volume of the lung on RP.Methods From Mar 2005 to Aug 2008, 161 patients with locally advanced NSCLC or esophageal carcinoma received 3DCRT. Fifty-three patients with NSCLC received radiotherapy of 60 Gy/30 -34 fx and concurrent chemotherapy of navelbine plus cisplatin (NP). Among the 108 patients with esophageal carcinoma with prescription doses ranging from 58 Gy/29 fx to 70 Gy/35 fx, 46 and 62 received 3DCRT alone or 3DCRT with concurrent chemotherapy of calcium folinate, 5-Fu and cisplatin (LFP), respectively. Univariate and multivariate analysis and receiver operating characteristics (ROC) curves were performed to assess the correlated factors of RP. Results The follow-up rate was 100%. The rate of RP was 57. 8% (93/161) for all patients, 94% (50/53,including 1 with Grade 4 and 1 with Grade 5) for patients with NSCLC, and 39.8% (43/108, none with Grade 4 and 5) for patients with esophageal carcinoma. The correlative factors included the sex, volume of gross tumor volume (GTV), mean lung dose (MLD), V5, V10, V15, V20, V25 and V30 of normal lung according to Spearman correlative analysis. Univariate analysis showed that all the 9 factors could predict RP. Only V5 and the volume of GTV were found independently associated with Grade 2 or more RP in multivariate analysis. ROC analysis indicated that the cut-off point of the curve was 55% with the area under ROC curve of 0. 684 (P = 0. 000). For the patients with lung V5 ≥ 55% and < 55% ,43% (36/84) and 18% (14/77) developed RP of Grade 2 or more, respectively. Conclusions Dosimetric parameters including MLD, normal tissue complication probability, and V5-V30 could predict RP. V5 may be the most valuable predictor. When V5 exceeds 55%, the probability of RP of grade 2 or more may increase notably. Besides the limitation of MLD, V20 and V30, the volume of low dose region should be also limited to a lower range during treatment planning. Key words: Lung neoplasms/radiotherapy; Esophagus neoplasms/radiotherapy; Radiotherapy,three-dimensional conformal; Radiation pneumonitis

Clinical outcomes of concurrent three-dimensional conformal radiotherapy and chemotherapy for limited-stage small cell lung cancer

Objective To evaluate therapeutic effects and complications of concurrent three-dimensional conformal radiotherapy (3DCRT) and chemotherapy in patients with limited-stage small cell lung cancer (LSCLC).Methods From June 2000 to August 2005, 93 histologically proved LSCLC patients were randomized into two groups:3DCRT group (n =46) and conventional group (n =47).In both groups, patients received one cycle chemotherapy, followed by concurrent chemoradiotherapy and then received consolidate chemotherapy.Chemotherapy was four to six cycles of PE regimen.Conventional irradiation field was setup in conventional group, while in 3 DCRT group clinical target volume (CTV) only involved visible tumor and adjacent lymphatic region.Radiotherapy was delivered at 2 Gy per fraction, 5 fractions per week to a median total dose of 60 -64 Gy.Those who achieved a complete response were treated with prophylactic cranial irradiation (PCI) with 30 Gy in 10 fractions.Results The follow-up rate was 100% in both groups.The number of patients completed 1-, 2-and 3-year follow-up were 36, 34 and 16 in 3DCRT group, 14, 7 and 8 in conventional group, respectively.The complete and overall response rate were 52% and 89% in 3DCRT group, while 47% and 85% in conventional group, respectively.The 1-, 2-and 3-year survival rates were 78%, 35% and 15% in 3DCRT group, 72%, 30% and 17% in conventional group, respectively.The median survival time was 23.2 and 22.8 months, respectively.There was no statistical difference in short-term (Χ~2 = 0.34 ,P = O.759) and long-term outcomes (Χ~2 = 0.18 ,P = 0.92).In 3DCRT group, the incidence of grade 1 +2 acute radiation pneumonitis and esophagitis, grade 1 +2 and grade 3 chronic radiation pneumonitis were lower than those in conventional group.There was no grade 3 or 4 acute radiation pneumonitis or esophagitis, or grade 4 chronic radiation pneumonitis in both groups.There was no difference in grade 1 + 2, grade 3 or grade 4 acute myelo-suppression between the two groups.Conclusions In the treatment of LSCLC, concurrent 3DCRT and chemotherapy can achieve satisfactory short-term and long-term outcomes with acceptable complications. Key words: Carcinoma, small cell lung/radiochemotherapy; Radiochemotherapy, concurrant; Radiotherapy,there-dimensional conformal; Prognosis

Analysis of clinical and dosimetric factors associated with severe acute radiation pneumonitis in patients with locally advanced non-small cell lung cancer treated with concurrent chemotherapy and intensity-modulated radiotherapy

BackgroundTo evaluate the association between the clinical, dosimetric factors and severe acute radiation pneumonitis (SARP) in patients with locally advanced non-small cell lung cancer (LANSCLC) treated with concurrent chemotherapy and intensity-modulated radiotherapy (IMRT).MethodsWe analyzed 94 LANSCLC patients treated with concurrent chemotherapy and IMRT between May 2005 and September 2006. SARP was defined as greater than or equal 3 side effects and graded according to Common Terminology Criteria for Adverse Events (CTCAE) version 3.0.The clinical and dosimetric factors were analyzed. Univariate and multivariate logistic regression analyses were performed to evaluate the relationship between clinical, dosimetric factors and SARP.ResultsMedian follow-up was 10.5 months (range 6.5-24). Of 94 patients, 11 (11.7%) developed SARP. Univariate analyses showed that the normal tissue complication probability (NTCP), mean lung dose (MLD), relative volumes of lung receiving more than a threshold dose of 5-60 Gy at increments of 5 Gy (V5-V60), chronic obstructive pulmonary disease (COPD) and Forced Expiratory Volume in the first second (FEV1) were associated with SARP (p < 0.05). In multivariate analysis, NTCP value (p = 0.001) and V10 (p = 0.015) were the most significant factors associated with SARP. The incidences of SARP in the group with NTCP > 4.2% and NTCP ≤4.2% were 43.5% and 1.4%, respectively (p < 0.01). The incidences of SARP in the group with V10 ≤50% and V10 >50% were 5.7% and 29.2%, respectively (p < 0.01).ConclusionsNTCP value and V10 are the useful indicators for predicting SARP in NSCLC patients treated with concurrent chemotherapy and IMRT.

Three-dimensional conformal radiotherapy for loco-regionally recurrent esophageal cancer after initial radiotherapy

Objective To evaluate the feasibility, therapeutic effects and normal tissue complications of three-dimensional conformal radiotherapy (3DCRT) for loco-regionally recurrent esophageal cancer after initial radiotherapy. Methods Between March 2001 and May 2007, 42 patients with loco-reigonal recurrent esophageal cancer after initial radiotherapy were treated with 3DCRT, including 27 male and 15 female with a median age of 67.5 years. Radiotherapy was delivered at 1.8 -2.0 Gy per fraction, 5 fractions per week, with a median total dose of 54 Gy. Treatment outcomes and normal tissue complications were assessed with WHO and RTOG/EORTC criteria. Results By December 31,2008, the follow-up rate was 100%. Twenty patients had follow-up time of 1 year and the remaining 22 had 2 years. The clinical symptom relief rate was 60%, and the response rate was 90.5% with a complete remission rate of 17% and partial remission rate of 74%. The overall 1- and 2-year survival (OS) rates were 60% and 24%. Grade 2 and grade 3 acute radiation esophagitis developed in 31% and 5% of the patients, respectively. Grade 2 and grade 3 acute radiation pneumonitis developed in 19% and 2% , respectively. Grade 2 and grade 3 acute radiation hematology toxicities developed in 5% and 2%, respectively. Conclusions For patients with loco-regional recurrences of esophageal cancer after initial radiotherapy, 3DCRT is feasible, with a good clinical symptom relief rate and immediate tumor response. However,the complication rate was high and the clinical indications should be strictly controlled. Key words: Esophageal neoplasms/radiotherapy; Radiotherapy, three-dimensional conformal; Prognosis

Predictive Factors of Late Radiation Fibrosis: A Prospective Study in Non–Small Cell Lung Cancer

To determine predictive factors of late radiation fibrosis (RF) after conformal radiotherapy (3D-RT) in non-small cell lung cancer (NSCLC). Ninety-six patients with Stage IA-IIIB NSCLC were included in a prospective trial. Clinical evaluation, chest X-ray, and pulmonary functional tests including diffusion parameters were performed before and 6 months after radiotherapy. An independent panel of experts prospectively analyzed RF, using Late Effects in Normal Tissues-Subjective, Objective, Management and Analytic scales classification. Logistic regression analysis was performed to identify relationships between clinical, functional, or treatment parameters and incidence of RF. Variations of circulating serum levels of pro-inflammatory (interleukin-6, tumor necrosis factor alpha, tumor growth factor beta1) and anti-inflammatory (interleukin-10) cytokines during 3D-RT were examined to identify correlations with RF. Of the 96 patients included, 72 were evaluable for RF at 6 months. Thirty-seven (51.4%) developed RF (Grade >or=1), including six severe RF (Grades 2-3; 8.3%). In univariate analysis, only poor Karnofsky Performance Status and previous acute radiation pneumonitis were associated with RF (p < 0.05). Dosimetric factors (mean lung dose, percentage of lung volume receiving more than 10, 20, 30, 40, and 50 Gy) were highly correlated with RF (p < 0.001). In multivariate analysis, previous acute radiation pneumonitis and dosimetric parameters were significantly correlated with RF occurrence. It was not significantly correlated either with cytokines at baseline or with their variation during 3D-RT. This study confirms the importance of dosimetric parameters to limit the risk of RF. Contrary to acute radiation pneumonitis, RF was not correlated to cytokine variations during 3D-RT.

Late course acceleratedthree-dimensional conformal radiotherapy for esophageal carcinoma

：Objective To investigatethe result and side effect of late course accelerated three-di-mensional conformalradiotherapy (3DCRT) for esophageal carcinoma. Methods From July 2003 to March 2006, 55patients with esophageal carcinoma receiving 3DCRT were randomly divided into late courseaccel-erated radiation group (group A, 27 patients) and conventional fractionation group(group B, 28 patients). The prescribed dose in group B was 64 -66 Gy, 2 Gy per fraction, 1fraction per day, 5 fractions per week for about 6.5 weeks. Patients in group A receivedconventional fractionation irradiation for the first 4 weeks. Then the dose was increasedto 3 Gy per fraction to a total dose of 67 -70 Gy. The treatment course in group A wasabout 6 weeks. The treatment response, acute site effects, 1-, 3-and 5-year local controlrates and o-verall survival rates of the two groups were observed. Results In group A, 23patients (85%) achievedcomplete response (CR) and 4(15%) achieved partial response (PR).While in group B, 16 patients (57%) achieved CR and 12(43%) achieved PR. The CR rate wassignificant higher in group A (χ~2 = 5.24,P=0.022). The 1-,3-, 5-year local control rates were 85%, 54%, 54% in group A, and 70%, 56%, 33 % in groupB (χ~2 = 0.68, P = 0.409), respectively. The 1 -,3-,5-year overallsurvival rates of the two groups were 81%, 37%, 29% and 61%, 39%, 23% (χ~2 =0.06, P = O. 804), respectively. Both lo-cal control and overall survival were similarbetween the two groups. The incidences of acute radiation esoph-agitis in the two groupswere similar (85% vs. 89% ;χ~2 =0. 00,P=0. 959), and theincidence of radiation pneumonitis was slightly higher in group A than in group B (67% vs43% ;χ~2=3.14,P =0.076). By the last follow up, 19 patients in group A and 21 in group B died.Among them, 10 in group A and 15 in group B died of local failure, while 7 in group A and5 in group B died of metastasis. Conclusions When com-pared with conventionalfractionation 3DCRT, late course accelerated 3DCRT for esophageal carcinoma can achievebetter results in clinical response, though not in long-term local control or survival.The incidence of acute radiation esophagitis and pneumonitis is clinically acceptable. Key words: Esophageal neoplasms/radiotherapy; Radiotherapy,three-dimensional conformal; Radiotherapy,late course accelerated; Prognosis

Toxicity risk of non-target organs at risk receiving low-dose radiation: case report

The spine is the most common site for bone metastases. Radiation therapy is a common treatment for palliation of pain and for prevention or treatment of spinal cord compression. Helical tomotherapy (HT), a new image-guided intensity modulated radiotherapy (IMRT), delivers highly conformal dose distributions and provides an impressive ability to spare adjacent organs at risk, thus increasing the local control of spinal column metastases and decreasing the potential risk of critical organs under treatment. However, there are a lot of non-target organs at risk (OARs) occupied by low dose with underestimate in this modern rotational IMRT treatment. Herein, we report a case of a pathologic compression fracture of the T9 vertebra in a 55-year-old patient with cholangiocarcinoma. The patient underwent HT at a dose of 30 Gy/10 fractions delivered to T8-T10 for symptom relief. Two weeks after the radiotherapy had been completed, the first course of chemotherapy comprising gemcitabine, fluorouracil, and leucovorin was administered. After two weeks of chemotherapy, however, the patient developed progressive dyspnea. A computed tomography scan of the chest revealed an interstitial pattern with traction bronchiectasis, diffuse ground-glass opacities, and cystic change with fibrosis. Acute radiation pneumonitis was diagnosed. Oncologists should be alert to the potential risk of radiation toxicities caused by low dose off-targets and abscopal effects even with highly conformal radiotherapy.

Risk factors of acute radiation pneumonitis in patients with non-small cell lung cancer after concur-rent three-dimensional conformal radiotherapy and chemotherapy

Objective To analyze the incidence and related factors of acute radiation pneumonitis (RP) in patients with non-small cell lung cancer (NSCLC) who underwent three-dimensional conformal ra-diotherapy with concurrent chemotherapy. Methods From January 2006 to October 2008, 90 NSCLC pa-tients treated with concurrent chemoradiotherapy were retrospectively reviewed. The clinical characteristics and treatment plan parameters from dose-volume histogram (DVH) were analyzed. Results Grade 1, 2,3, 4 and 5 RP was found in 32.2%, 30.0%, 5.6%, 0% and 1.1% of the patients. Primary tumor loca-tion was the only significant clinical factor in univariate analysis. And significant differences were found when the groups was divided by the mean lung dose (MLD) of 17 Gy, V5 of 47% ,V10 of 36% ,V20 of 24%,V30 of 23% and V40 of 22%, respectively. Multivariate analysis showed the MLD was the only independent predictive factor of RP. Conclusions Some factors may contribute to the RP. MLD should be set below 17 Gy in three-dimensional conformal radiation, especially when the tumor locates in the lower lobe. Key words: Lung neoplasms/radiotherapy; Radiotherapy, three-dimensional conformal; Lung neoplasms/chemotherapy; Chemotherapy,concurrent; Radiation pneumonitis; Factor analysis

Facteurs prédictifs de la pneumopathie radique aiguë

Thoracic irradiation is a major weapon in the treatment of nonmetastatic primary lung cancer, in particular in patients presenting a locally advanced disease of the mediastinium. Acute radiation pneumonitis (ARP) is one of the main limiting toxicities. The purpose of this work is to sum up the current state of knowledge of the factors of risk of developing ARP. The incidence after conventional irradiation, in patients with non small cell lung cancer (NSCLC) is about 7 to 10% in the moderate although symptomatic forms of ARP and about 1 to 3% in the severe forms. The factors related to the patient, the tumour or treatments prior to the irradiation do not determine any specific risk of ARP besides an age of over 65 years that remains debatable. The validated predictive factors of ARP are mainly related to the irradiation factors (healthy lung volumes irradiated, average dose of irradiation, etc.). Nevertheless, in spite of the adjustment of these parameters, the individual susceptibility to the toxicity of thoracic radiotherapy remains significant, directing current research to the biological markers intrinsic to the patient. In particular, the involvement of early variations of certain cytokines (IL-6, IL-10, TGF-ss) in the occurrence of ARP during irradiation has been suggested and studies are under way to confirm their involvement and determine their role.