ABSTRACT
Indoleamine 2, 3-dioxygenase (IDO) is one of the rate-limiting enzymes that degrade tryptophan (Trp) into kynurenine (Kyn). Inflammatory factor IFN-γ mediates tumor′s immune escape by activating the IDO signaling pathway, upregulating theKyn/Trp (K/T ratio) and suppressing the activity of both CD 8+T and regulatory T cells. Radiotherapy plays a major role in treating non-small cell lung cancer. It not only bi-directionally regulates immune response of the host, but also collaborates with immunosuppressive agents to kill tumors. Meanwhile, immune status of the host can affect the therapeutic effect of radiotherapy. In recent years, studies have shown that IDO activity levels change before and after radiotherapy and is related to clinical prognosis. Nevertheless, relevant mechanism remains unclear. This article aims to elucidate the application of IDO signaling pathway in radiotherapy for non-small cell lung cancer.
ABSTRACT
Radiotherapy is the common traditional treatment for non-small cell lung cancer (NSCLC).In recent years,remarkable advances have been made in immunotherapy,especially the use of immune checkpoint inhibitors.How to effectively combine radiotherapy and immunotherapy to maximize the benefit for patients has become a hot topic in clinical research.This article expounds recent research progress in immunotherapy for NSCLC,the effect of radiotherapy on tumor immunology,and the advances and challenges in radiotherapy combined with immunotherapy for NSCLC.
ABSTRACT
Currently,lung cancer is the most common malignant tumor in the world.The local control (LC) rate is only 20％-40％ for patients with local advanced non-small cell lung cancer (NSCLC).Hence,reducing the LC rate and enhancing the overall survival (OS) are pivotal research objectives.However,postoperative adjuvant treatment for patients with early NSCLC with chest wall invasion is still controversial.In this article,the research progress on T3 N0-1M0 NSCLC with chest wall invasion was reviewed from the perspectives including anatomical features,types of resection,patterns of failure and postoperative radiotherapy,etc.
ABSTRACT
Objective To compare the clinical efficacy and safety between stereotactic ablative radiotherapy (SABR) and surgery in the treatment of early-stage non-small cell lung cancer (NSCLC).Methods A total of 227 patients who were initially diagnosed with early-stage NSCLC and with complete clinical data admitted to Henan Cancer Hospital between June 2012 and December 2016 were recruited and assigned into the SABR (n=73) and surgery groups (n=154).Kaplan-Meier method was used to calculate survival rate and survival comparison was performed using the log-rank test.Chi-square test was adopted to compare the baseline data between two groups.Results All patients completed corresponding treatment.The samples of SABR group and operation group were 74 and 155 cases respectively.The 1-year and 3-year overall survival (OS) rates in the SABR and surgery groups were 97.2％,81.9％ and 96.5％,78.2％ (P=0.603),respectively.The 1-year and 3-year progression-free survival (PFS) rates in the SABR and surgery groups were 90.1％,66.9％ and 89.2％,66.9％ (P=0.565),respectively.The 1-year and 3-year locoregional recurrence free survival rates in the SABR and surgery groups were 92.8％,84.0％ and 96.5％,90.8％ (P=0.133),respectively.The 1-year and 3-year distant metastasis-free survival rates in the SABR and surgery groups were 97.2％,75.4％ and 89.2％,69.8％ (P=0.095),respectively.Conclusions SABR and surgery yield similar OS,PFS,locoregional recurrence-free and distant metastasis-free survival rates in the treatment of early-stage NSCLC.Therefore,SABR is an alternative treatment for patients with early-stage NSCLC.
ABSTRACT
Objective To investigate the consensus and controversies on the delineation of radiotherapy target volume for patients with locally advanced non-small cell lung cancer (LA-NSCLC).Methods Questionnaires including 15 questions on the delineation of radiotherapy target volume of NSCLC were sent to 12 radiation departments in China in November 2015.A patient with LA-NSCLC was selected by Fudan University Shanghai Cancer Center, and simulation CT images and medical history data were sent to the 12 radiation departments.Twelve radiation oncologists from the 12 radiation departments showed and explained the delineation of radiotherapy target volume of their own, and the patient was discussed by all experts in the sixth multidisciplinary summit forum of precise radiotherapy and chemotherapy for tumor and lung cancer.Results All receivers of the questionnaire answered the questions.The standard lung window width/level for the delineation of lung cancer was 800-1600/-600 to-750 HU, and the mediastinum window was 350-400/20-40 HU.Respiratory movement was measured by stimulator, 4D-CT, and stimulator+4D-CT with 2-5 mm expansion based on experience.The primary clinical target volume (CTV) was defined as gross target volume (GTV) plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma.The metastatic lesion of mediastinal lymph nodes was delineated as 5 mm plus primary lesion in 6 departments and as primary lesion in another 6 departments.Of the 12 departments, 10 applied 5 mm of set-up error, 1 applied 3 mm, and 1 applied 4-6 mm.For V20 of the lungs, 10 departments defined it as<30%, 1 as<35%, and 1 as 28%.Nine departments defined the radiation dose of concurrent chemoradiotherapy (CCRT) for LA-NSCLC as 60 Gy in 30 fractions, 62.7 Gy in 33 fractions in 1 department, 50-60 Gy in 25-30 fractions in 1 department, and 60-70 Gy in 25-30 fractions in 1 department.For the delineation of target volume for the LA-NSCLC patient treated with CCRT, the primary planning target volume (PTV) was defined as GTV plus organ movement (IGTV) and set-up error (GTV→IGTV→PTV) in 3 departments, as CTV plus organ movement (ITV) and set-up error (GTV→CTV→ITV→PTV) in 8 departments, and as CTV plus set-up error/IGTV plus 5-6 mm for squamous carcinoma/5-8 mm for adenocarcinoma (CTV) and set-up error (GTV→CTV→PTV/GTV→IGTV→CTV→PTV) in 1 department.For the delineation of PTV in the mediastinal lymph node, GTV→IGTV→PTV was performed in 3 departments, GTV→CTV→ITV→PTV in 8 departments, and GTV→CTV→PTV in 1 department.For 10%-100% patients with LA-NSCLC, the radiation field needed to be replanned when 38-50 Gy was completed.There was no unified standard for the optimal standardized uptake value (SUV) of positron emission tomography (PET)-computed tomography (CT) simulation and delineation.Seven departments had applied magnetic resonance imaging (MRI) simulation and 10 departments had applied stereotactic body radiation therapy (SBRT) for the treatment of early-stage NSCLC.For the delineation of PTV for early-stage NSCLC (T1-2N0M0), GTV→IGTV→PTV was performed in 5 departments, IGTV→PTV in 3 departments, and GTV→CTV→ITV→PTV in 2 departments.In all the 12 departments, peripheral early-stage NSCLC was given 6.0-12.5 Gy/fraction, 3-12 fractions and central early-stage NSCLC was given 4.6-10.0 Gy/fraction, 5-10 fractions.The results of discussion on the delineation of target volume for the patient were as follows:respiratory movements should be measured by 4D-CT or simulator;the lung window width/level is 1600/-600 HU and the mediastinal window width/level is 400/20 HU;the primary controversy is whether the involved-field irradiation or elective nodal irradiation should be used for the delineation of CTVnd in the mediastinal lymph node.Conclusions Basic consensus is reached for the delineation of target volume in LANSCLC in these aspects:lung window width/level, respiratory movements and set-up error, primary lesion delineation, the radiation dose in CCRT, and the optimal time for replanning the radiation field.There are controversies on the optimal SUV in the delineation of target volume based on PET-CT simulation, the optimal dose fractionation in SBRT for early-stage NSCLC, and the delineation of CTVnd.
ABSTRACT
Stage Ⅲ A non-small cell lung cancer (NSCLC) has high heterogeneity and there are some controversies over the treatment of this disease,especially for patients with stage ⅢA-N2 NSCLC.This article investigates whether preoperative or postoperative radiotherapy can improve the survival of patients with stage ⅢA-N2 NSCLC and evaluates the effect of surgical treatment.
ABSTRACT
Epidermal growth factor receptor ( EGFR) is most popular in targeted therapy for non-small cell lung cancer ( NSCLC ) . In recent years, there have been a great number of molecular biology studies of EGFR. Radiotherapy is well-known as a traditional and important treatment for NSCLC, and the treatment outcome is associated with EGFR mutation and overexpression. Phase Ⅲ trials are needed to evaluate the effect of a combination of radiotherapy and EGFR-tyrosine kinase inhibitor ( EGFR-TKI) in the treatment of NSCLC. MicroRNAs ( miRNAs) can modulate tumor-associated gene expression and influence the biological process of tumor. Recent studies have demonstrated that miRNAs play a positive or negative role in EGFR mutation, EGFR-TKI treatment, and radiotherapy, which mechanism has been partially clarified. In this article, we review the research advances in the association of miRNAs with EGFR mutation, EGFR-TKI, and radiotherapy, so as to provide the latest evidence for the application of miRNAs in the combination of radiotherapy and EGFR-TKI for the treatment of NSCLC.
ABSTRACT
Epidermal growth factor receptor ( EGFR) is most popular in targeted therapy for non-small cell lung cancer ( NSCLC ) . In recent years, there have been a great number of molecular biology studies of EGFR. Radiotherapy is well-known as a traditional and important treatment for NSCLC, and the treatment outcome is associated with EGFR mutation and overexpression. Phase Ⅲ trials are needed to evaluate the effect of a combination of radiotherapy and EGFR-tyrosine kinase inhibitor ( EGFR-TKI) in the treatment of NSCLC. MicroRNAs ( miRNAs) can modulate tumor-associated gene expression and influence the biological process of tumor. Recent studies have demonstrated that miRNAs play a positive or negative role in EGFR mutation, EGFR-TKI treatment, and radiotherapy, which mechanism has been partially clarified. In this article, we review the research advances in the association of miRNAs with EGFR mutation, EGFR-TKI, and radiotherapy, so as to provide the latest evidence for the application of miRNAs in the combination of radiotherapy and EGFR-TKI for the treatment of NSCLC.
ABSTRACT
Conventional CT plays an important role in the diagnosis, staging, radiotherapy target delineation, and prognosis of NSCLC, but it still has many limitations.PET/CT has been widely used in the diagnosis and treamtent of lung cancer.In particular, PET/CT metabolic parameters have great guiding significance in the prognosis of NSCLC patients undergoing radiotherapy, and may be superior to many clinical indices.This review summarizes the advances in the application of PET/CT in the prognostic evaluation of NSCLC patients undergoing radiotherapy.
ABSTRACT
ObjectiveTo evaluate the efficacy, feasibility and safety of CT guided percutaneous 125Ⅰ seeds implantation in elderly patients of stage Ⅰperipheral non-small cell lung cancer ( NSCLC ).MethodsClinical data of 16 elderly peripheral stage Ⅰ NSCLC patients ( 10 squamous carcinoma and 6adenocarcinoma;13 stage ⅠA and 3 stage ⅠB ) who received radioactive 125Ⅰ seeds implantation because of refusal or being unsuited to operation or external radiotherapy were retrospectively analyzed. Prescribed dose was 140 - 160 Gy. Under CT guidance, 125Ⅰ seeds were implanted percutaneously into tumors for interstitial radiotherapy according to treatment plan system. ResultsMean number of 125Ⅰ seeds each patient received was21.1. 12 complete response (CR) and 4 partial response (PR) were achieved. Total response rate ( CR + PR) was 100％. 100％ patients completed 10 to 56 months of follow-up, 15, 13, 8 and 6 patients completed 1-, 2-, 3-and 4-years'follow-up, respectively. The median local progression free time was 14months. The 1-,2-,3-and 4-year overall survival rate were 60％, 54％, 50％ and 33％, respectively (median:14 months). 7 cases died of non-tumor disease and 5 died of metastasis. No severe complications were observed. ConclusionsCT guided 125Ⅰ seeds implantation is a safe, reliable and effective radical treatment method for elderly stage Ⅰ peripheral NSCLC patients, who refuse to or are unsuitable to operation or external radiotherapy.
ABSTRACT
ObjectiveTo investigate prognostic factors in Stage Ⅲ non-small cell lung cancer (NSCLC)treated with definitive radiation therapy (RT) with PET-CT-based radiotherapy planning. MethodsFifty nine patients with Stage Ⅲ NSCLC treated with radiation therapy of 60 Gy or more were enrolled into this study.The impact of prognostic factors on survival was evaluated by univariate and multivariate analyses. Results The following-up rate was 98％.Nineteen patients completed 2 years' followed-up. The overall l-year and 2-year survival rate was 66％ and 37％, respectively, with a median survival time of 17 months. At a univariate analysis, cigarette smoking status, T stage, radiation dose, the standardized uptake value, the gross tumor volume and clinical stage were significant prognostic factors ( x2 =7.46,7. 52,8.37,4. 97,5.82,4. 37, P =0. 006,0. 006,0. 004,0. 026,0. 016,0. 037, respectively ).At multivariate analyses, cigarette smoking status, radiation dose, gross tumor volume and clinical stage were significant prognostic factors ( x2 =6. 20, 9. 69, 6. 39, 10. 09, P =0. 013,0. 002, 0. 011,0. 001,respectively). Conclusions Cigarette smoking status, radiation dose, gross tumor volume and clinical stage are significant prognostic factors on survival in patients with Stage Ⅲ NSCLC treated with RT based on PET-CT radiotherapy planning.
ABSTRACT
Objective To compare positional and volumetric differences of internal gross tumor volume (IGTV) delineated separately by three approaches based on four-dimensional CT (4DCT) for the primary tumor of non-small cell lung cancer (NLCLC). Methods Twenty-one patients with NLCLC underwent big bore 4DCT simulation scan of the thorax. IGTVs of the primary tumor of NSCLC were tumor on the MIP images were delineated to produce IGTVMIP. The position of the target center, the volume of target, the degree of inclusion (DI) and the matching index (MI) were compared reciprocally between IGTV10, IGTVEI+EE and IGTVMIP. Results Average differences between the position of the center of IGTVs on direction of x,y and z axes were less than 1 mm, with no statistically significant difference. The volume of IGTV10 was larger than that of IGTVEI+EE, the difference was statistically significant (t=2.37,P=0.028);the volume of IGTV10 was larger than that of IGTVMIP, but the difference was not statistically significant(t=1.95 ,P=0.065). The ratio of IGTVEI+EE with IGTV10, IGTVMIP with IGTV10 were 0.85±0.08 and 0.92±0.11, respectively. DI of IGTVEI+EE in IGTV10, IGTVMIP in IGTV10 were 84.78% ± 8. 95% and 88.47% ±9.04%. MI between IGTV10 and IGTVEI+EE, IGTV10 and IGTVMIP were 0.85 ±0.09, 0.86±0. 09, respectively. Conclusions The center displacement of the IGTVs delineated separately by the three different techniques based on 4DCT images are not obvious; IGTVEI+EE and IGTVMIP can not replace IGTV10 , however , IGTVMIP is more close to IGTV10 comparing to IGTVEI+EE . The ratio of GTVEI+EE with IGTV10 is correlated to the tumor motion vector. As the vector increases, the ratio of GTVEI+EE with IGTV10decreases, especially for small tumors.
ABSTRACT
Objective To evaluate the therapeutic efficacy and treatment-related toxicity of stereotactic body radiation therapy(SBRT)in patients with medically inoperable stage Ⅰ/Ⅱ non-small cell lung cancer(NSCLC). Methods SBRT was applied to 30 patients, including clinically staged T1 ,T2(≤5cm)or T3(chest wall primary tumors only), N0, M0 ,biopsy-confirmed NSCLC. All patients were precluded from lobotomy because of physical condition or comorbidity. No patients developed tumors of any T-stage in the proximal zone. SBRT was performed with the total dose of 50 Gy to 70 Gy in 10 - 11 fractions during 12 - 15 days. prescription line was set onthe edge of the PTV. Results The follow-up rate was 100%. The number of patients who completed the 1-, and 2-year follow-up were 15, and 10, respectively. All 30 patients completed therapy as planned. The complete response(CR), partial response(PR)and stable disease(SD)rates were 37%, 53% and 3%, respectively. With a median follow-up of 16 months(range,4-36 months), Kaplan-Meier local control at 2 years was 94%. The 2-year overall survival was 84% and the 2-year cancer specific survival was 90%. Seven patients(23%)developed Grade 2 pneumonitis, no grade ＞ 2 acute or late lung toxicity was observed. No one developed chest wall pain. Conclusions It is feasible to deliver 50 Gy to 70 Gy of SBRT in 10 - 11 fractions for medically inoperable patients with stage Ⅰ / Ⅱ NSCLC. It was associated with low incidence of toxicities and provided sustained local tumor control.The preliminary investigation indicated the cancer specific survival probability of SBRT was high. It is necessary to perform similar investigation in a larger number of patients with long-term follow-up.
ABSTRACT
Objective To analyze the factors affecting the efficacy of postoperative radiotherapy (PORT) in node-positive non-small cell lung cancer (NSCLC). Methods 480 patients with stage N_1-N_2 NSCLC after radical surgery were retrospectively reviewed. Of them, 267 patients received adjuvant chemotherapy and 121 received PORT. All patients were grouped based on the N stage, tumor size and lymph node positive ratio (the percentage of positive lymph nodes from the detected lymph nodes, LNPR). Group 1 included patients with tumor size ≤3 cm and LNPR ≤33%, group 2 was tumor size > 3 cm or LNPR > 33%, and group 3 was tumor size > 3 cm and LNPR > 33%. The endpoints were the local recurrence free survival (LRFS) and overall survival (OS). Kaplan-Meier method and Cox's proportional hazards regression model were used for the statistic analyses. Results PORT improved the overall survival only in patients with N_2 disease. Both tumor size and LNPR significantly influenced the efficacy of PORT. The 5-year LRFS for patients with vs. without PORT in the group 1, 2 and 3 were 55% vs. 60% (χ~2 = 0.03,P-0.869), 42% vs. 50% (χ~2 =0.31,P=0.547),and 62% vs. 52% (χ~2=4.25,P=0.036), respectively;and the corresponding OS were 22% vs. 50% (χ~2 = 1.65 ,P =0. 199), 26% vs. 22% (χ~2= 0. 13,P=0.786) and 42% vs. 16% (χ~2= 15.33,P=0.000), respectively. Conclusions Tumor size and LNPR significantly impact the efficacy of PORT . For patients with stage N_2 NSCLC , PORT could improve local recurrence free survival and overall survival when tumor size > 3 cm and LNPR >33%.
ABSTRACT
Objective To evaluate the feasibility of active breathing control (ABC) in conformal radiotherapy (CRT) for patients with non-small cell lung cancer (NSCLC). Methods From Feb 2005 to Mar 2008, 29 patients with inoperable NSCLC (stage Ⅱ-Ⅳ) were evaluated. For each patient, two series of CT scans were obtained with free breathing (FB) and ABC system during simulation, respectively. Then two confonnal radiotherapy (CRT) plans were finished based on the two sets of reconstructed images. The pattern of post-inspiratory breath-hold was triggered at 80% of the peak of inspiration curve. The margin of clinical target volume (CTV) to planning target volume (PTV) was 0. 6 cm for lesions of the superior lobe, and 1.0 cm for the lesions of middle and inferior lobes. Three to five coplanar fields were performed in conformal radiotherapy. The gross tumor volume (GTV), CTV, PTV, volume of the bilateral lungs (Volume_(lung)), V_(20) and mean lung dose (MLD) of two plans were evaluated by dose-volume histogram (DVH). The World Health Organization criteria and National Cancer Institute Common Toxicity Criteria 3.0 (NCI-CTC3.0) scale were used to assess the immediate response and acute side-effect, respectively. Results Significant differences of GTV, CTV, FIN, Volum_(lung), V_(20) and MDL were observed between the two plans (36. 35 cm~3 vs. 31.40 cm~3, t = 9. 70, P <0. 001 ;82. 33 cm~3 vs. 70. 83 cm~3, t = 8. 19, P < 0. 001 ; 230. 73 cm~3 vs. 197.59 cm~3 ,t=5.72,P <0. 001 ;21.66% vs. 18. 76% ,t = 11.16,P <0. 001 ;1329. 07 Gy vs. 1143. 14 Gy, t = 13. 24, P < 0. 001). With ABC, all patients completed their treatment successfully except one patient for financial problems. The median radiation dose to the GTV was 64 Gy (60 -64 Gy). The overall immediate response rate was 64% (18/28). According to the NCI-CTC 3.0, grade 1 and 2 acute radiation-related toxicities occurred in 68% (19/28) and 18% (5/28) of patients for esophagitis, 82% (23/28) and 7% (2/28) for pneumonitis, respectively. Grade 1, 2 and 3 bone marrow suppression occurred in 57% (16/28), 25% (7/28) and 14% (4/28) of patients, respectively. Grade 1 and 2 acute cardiac injuries occurred in 86% (24/28) and 14% (4/28) of patients. Conclusions During CRT for patients with NSCLC, the use of ABC can decrease the radiation dose and acute complications of normal tissues.
ABSTRACT
Objective To analyze relation of comprehensive parameters of the dose-volume V5,V10 and V20 with radiation pneumonitis (RP) in patients with advanced stage non-small-cell lung cancer (NSCLC) treated with three-dimensional conformal (3DCRT) or intensity-modulated radiation therapy (IMRT).Methods Data of 90 patients with histologically proved NSCLC treated with 3DCRT or IMRT between November 2006 and July 2009 were collected.The median radiation dose of 70 Gy (range, 61 - 80 Gy) was delivered with late-course accelerated hyperfractionated radiotherapy (LAHRT).The V5 ,V10 ,V20,V30 and mean lung dose (MLD) were calculated from the dose-volume histogram system.The RP was evaluated according to the common toxicity criteria 3.0(CTC 3.0).Results The range of V5 ,V10 and V20 was 36% - 98%, 27% - 78% and 19% - 54%, respectively, with a median value of 66%, 48% and 31%, respectively.The RP of grade 1,2,3,4 and 5 was observed in 29,23,5,1 and 1 patients.The V5,V10 ,V20, contralateral V10, GTV,PTV, and numbers of fields were all significantly associated with RP of ≥grade 1 (χ2=2.04, 2.05, 2.01, 4.62, 6.50, 5.61, 5.61, and P= 0.044, 0.043, 0.047, 0.030,0.010,0.020,0.020).The V5, V10, V20, V30, and MLD were all significantly associated with RP of ≥ grade 2 (χ2= 2.05,2.20,2.96,4.96,5.20, and P = 0.040,0.030,0.000,0.030,0.020).In Logistic regression analysis, GTV was the only factor significantly associated with RP of ≥ grade 1 (χ2= 4.06, P =0.044).The V20 was the only factor significantly associated with RP of ≥grade 2(χ2=9.61,P=0.002).The RP of ≥grade 2 was significantly increased when V20 was more than 31%.The RP of ≥grade 2 was significantly increased when V20, V10 and V5 were more than 31%, 48% and 66%, respectively.The RP of ≥ grade 2 was significantly increased when V20 was more than 31% and V5 was more than 66%.Conclusions The comprehensive parameters combined with V5, V10 and V20 are effective in predicting RP.
ABSTRACT
Objective To retrospectively analyze treatment results of radiotherapy for medically inoperable stage Ⅰ/Ⅱ non-small cell lung cancer. Methods Between Jan.2000 and Dec.2005,fifty-eight such patients were enrolled into the database analysis,including 37 with clinical stage Ⅰ and 21 with stage Ⅱ disease.Fifty patients received radiotherapy alone and eight with radiotherapy and chemotherapy.Fortythree patients were treated with 3-D conformal radiotherapy(3D-CRT)and 15 with conventional radiotherapy.Results The 1-,2-and 3- year overall survival rates were 85%,54%and 30%,and the median survival time was 26.2 months for the whole group.The corresponding figures were 88%,60%,36%and 30.8 months for cancer-specific survival:84%,64%,31%and 30.8 months for Stage Ⅰ disease;81%,47%,28%and 18.8 months for Stage Ⅱ disease;95%,57%,33%and 30.8 months for 3D-CRT group and 53%,44%,24%and 15.3 months for conventional radiotherapy group.By logrank test,tumor volume,pneumonitis of Grade Ⅱ or higher and weight loSS more than 5%showed statistically significant impact on overall survival.Tumor volume was the only independent prognostic factor in Cox muhivariable regression.Pneumonitis and esophagitis of Grade Ⅱ or higher were 16%and 2%,respectively.Age and lung function before treatment had a significant relationship with pneumonitis.Failure included the local recurrence(33%)and distant metastasis(21%).There was no difference between the treatment modalities and failure sites. Conclusions For medically inoperable early stage non-small cell lung cancer patients,tumor volume is the most important prognostic factor for overall survival.The conformal radiotherapy marginally improves the survival.The age and pulmonary function are related to the incidence of treatment induced pneumonitis.
ABSTRACT
Objective To evaluate the accuracy, of different threshold segmentation of 18FDG PET for target volume delineation of non-small cell lung cancer(NSCLC) and the potential influence on radiotherapy treatment planning. Methods Eight NSCLC patients who had tumor with clear margin on CT scan and the amplitude of tumor movements not more than 5 mm were enrolled. PET scans were carried out at 1 h after intravenous injection of 18FDG with CT image for attenuation revisement. Gross target volume (GTV) delineated on CT image ( GTVCT ) was used as the standard. Then, GTVs were delineated on PET image with three different threshold segmentation of 42% Imax(total) (42% of maximum voxel intensity within the tumor) ,Iback + 20% Imax-back(max) (mean background intensity + 20% of normalized background-subtracted maximum voxel intensity within the tumor) and Iback -20% Imax-back(slice) (mean background intensity + 20% of normalized background-subtracted maximum voxel intensity of each slice within the tumor) ,the corresponding GTV was named as GTV42%, GTV20%max and GTV20%slice. Both the size of GTV42%, GTV20%max, GTV20%slice and GTVCT,and the coverage over GTVCT for each GTV were compared. A three dimensional margin of 1 cm were added to GTVCT, GTV42%, GTV20%max and GTV20%slice to form corresponding PTVCT, PTV42%, PTV20%max and PTV20%slic e. Three dimensional conformal radiotherapy treatment plans were designed based on PTVCT,PTV42% , PTV20%max and PTV20%slice respectively for each patient. The prescription dose of all PTVs was 66 Gy in 33 fractions in 6.6 weeks. Both the volume accepting dose less than 95% of prescription dose within PTVCT ( VPTV ) and the lung V20 were compared among the four plans based on different PTVs. Tumor control probability(TCP) as well as lung normal tissue complication probability (NTCP) were also compared. Resuits Eight patients were enrolled in this study. Median deviation of volume between GTVPET and GTVCT were -54.1% , -21.5 % and 5.3 % for GTV42% , GTV20%max and GTV20%slice, respectively. Median coverage over GTVCT of GTV42% , GTV20%max and GTV20%slice was 45.9% ,78.0% and 95.3% respectively( F = 57.50,P＜0.01). Median 7.5% of VPTV was observed for radiotherapy treatment plan based on PTV42% ,which meant that it might induce median 1% decrease of TCP comparing with that of radiotherapy treatment plan based on PTVCT. Whereas,there were only 1.3% and 0.0% of VPTV for treatment plans based on PTV20%max and PTV20%slice respectively. As far as TCP was concemed, both PTV20%max group and PTV20%slice group were superior to PTV42% group,there was no significant difference among PTV20%max group, PTV20%slice group and PTVCT group. Lung V20 and lung NTCP showed no significant difference among all groups. Conclusions The threshold segmentation of Iback + 20% Imax-back(slice) , being slice specialized, might be an optimal threshold segmentation for target volume delineation of lung caner. Independent of information of target volume provided by CT scan in advance,it is recommended to use for the target volume delineation of NSCLC with atelectasis.
ABSTRACT
Objective To evaluate the toxicity and efficacy of induction chemotherapy(ICT)followed by three-dimensional conformal radiotherapy(3 DCRT)plus concurrent weekly paclitaxel for inoperable non-small cell lung cancer(NSCLC). Methods Patients with stage Ⅲ NSCLC in favorable conditions were treated with 2 to 4 cycles of carboplatin(AUC=5-6,d1)combined with paclitaxel(175 mg/m2,d1),then followed by weekly paclitaxel(40 mg/m2)and concurrent 3DCRT within 3-4 weeks.The prescription dose of radiotherapy was given as high as possible while total lung V20≤31% and total dose of the spinal cord ≤50 Gy. Results ICT was well tolerated.During the concurrent chemoradiotherapy,the treatment of 4 patients was ended ahead of the schedule because of severe pulmonary and cardiac toxicities:the treatment of 2 patients was delayed for 7 and 12 days because of fatigue.Leucopenia(33/56)was in grade 1-2 except 1 patient in grade 3.Lymphocytopenia was severe(54/56,42 in grade 3).Three patients developed grade 3 acute radiation-induced esophagitis.and 3 developed grade 3-4 radiation-induced pneumonitis.There was one patients each who developed grade 2,3,and 4 late esophagealdamage,respectively.Nine developed grade 2 pulmonary fibrosis.The overall response rate was 69.7%.The 1-year overall survival rate was 72.3%.The 1-year local progression-free survival rate was 62.7%. Conclusions The schedule of ICT followed by weekly paclitaxel and concurrent 3DCRT can be well tolerated by most of the favorable patients with stageⅢ NSCLC.and the toxicity is tolerable. Results of this study are encouraging, though long-term results should be followed up.