Background: Tumor motion may compromise the accuracy of liver stereotactic radiotherapy. In order to carry out a precise planning, estimating liver tumor motion during radiotherapy has received a lot of attention. Previous approach may have difficult to deal with image data corrupted by noise. The iterative closest point (ICP) algorithm is widely used for estimating the rigid registration of three-dimensional point sets when these data were dense or corrupted. In the light of this, our study estimated the three-dimensional (3D) rigid motion of liver tumors during stereotactic liver radiotherapy using reconstructed 3D coordinates of fiducials based on the ICP algorithm. Methods: Four hundred ninety-five pairs of orthogonal kilovoltage (KV) images from the CyberKnife stereo imaging system for 12 patients were used in this study. For each pair of images, the 3D coordinates of fiducial markers inside the liver were calculated via geometric derivations. The 3D coordinates were used to calculate the real-time translational and rotational motion of liver tumors around three axes via an ICP algorithm. The residual error was also investigated both with and without rotational correction. Results: The translational shifts of liver tumors in left-right (LR), anterior-posterior (AP),and superior-inferior (SI) directions were 2.92 +/- 1.98 mm, 5.54 +/- 3.12 mm, and 16.22 +/- 5.86 mm, respectively; the rotational angles in left-right (LR), anterior-posterior (AP), and superior-inferior (SI) directions were 3.95 degrees +/- 3.08 degrees, 4.93 degrees +/- 2.90 degrees, and 4.09 degrees +/- 1.99 degrees, respectively. Rotational correction decreased 3D fiducial displacement from 1.19 +/- 0.35 mm to 0.65 +/- 0.24 mm (P<0.001). Conclusions: The maximum translational movement occurred in the SI direction. Rotational correction decreased fiducial displacements and increased tumor tracking accuracy.
Background Re-irradiation (re-RT) has the active effect of relieving clinical symptoms and prolonging the survival of patients with recurrent esophageal squamous cell carcinoma (ESCC). However, the optimal re-RT dose is still uncertain. Here, we analyzed the prognostic factors associated with survival and explored the optimal re-RT dose for patients with recurrent ESCC following definitive radiotherapy. Patients and methods The data of 47 patients with recurrent ESCC who were retreated between 2010 and 2014 were retrospectively analyzed. All patients received a radiation dose > 50 Gy during the primary treatment. The median time to recurrence after primary radiotherapy was 26 months (range 6-120 months). All patients had in-field recurrence in the esophagus. Recurrence within the local site was observed in 37 patients (78.7%), and recurrence in both the local site and regional nodes were observed in 10 patients (21.3%). All patients received 3D conformal re-RT with a median dose of 58 Gy (range 26-64 Gy). Chemotherapy was sequentially used in 27.7% of the patients. Survival curves were constructed according to the Kaplan-Meier method and were compared by log-rank tests. The factors predictive of survival were identified with univariate and multivariate analyses. Results Dysphagia relief after re-RT was achieved in 20 of the 35 symptomatic patients (57.1%). The median survival time (MST) of all patients was 17 months, and the 1-, 2-, 3- and 5-year overall survival (OS) rates were 72.3, 25.5, 17.0 and 2.1%, respectively. In the univariate analysis, an Eastern Cooperative Oncology Group Performance Status (ECOG-PS) of 0-1 (P = 0.014), recurrence at the local site (P = 0.048), time to recurrence >= 24 months (P = 0.006) and re-RT dose >= 50 Gy (P < 0.001) were associated with favorable OS. In the multivariate analysis, only re-RT dose was an independent factor for OS (P = 0.007). Severe complications were observed in 7 patients, two of whom received a re-RT dose > 60 Gy. Conclusion Our results demonstrated that patients with recurrent ESCC following definitive radiotherapy had unfavorable OS. Re-RT could be considered a feasible and effective treatment modality. A re-RT dose > 50 Gy could improve the survival outcomes, and a dose > 60 Gy should be administered with caution due to the risk of severe complications.
Background We aimed to ascertain population-based practice patterns and survival outcomes of postoperative radiotherapy following breast conserving-surgery (BCS) in elderly women (aged >= 65 years) with early-stage pure mucinous breast carcinoma (PMBC). Methods Patients aged >= 65 years diagnosed with T1-2N0 and hormone receptor-positive PMBC between 1990 and 2010 were identified from the Surveillance, Epidemiology, and End Results database. Binomial logistic regression, Kaplan-Meier method, Multivariate Cox proportional hazards models, and propensity score matching (PSM) were used for statistical analysis. Results We enrolled 3416 patients, including 1225 (35.9%) and 2191 (64.1%) in the no-radiotherapy and radiotherapy cohorts, respectively. The percentage of patients receiving postoperative radiotherapy following BCS was significantly lower after 2004 (59.5% between 2004 and 2010), relative to that before 2004 (71.1% between 1990 and 2003; P < 0.001). Before PSM, the 10-year breast cancer-specific survival (BCSS) rates were 98.1 and 93.2% for patients with and without postoperative radiotherapy (log-rank test, P < 0.001), respectively. In the PSM cohort, receiving postoperative radiotherapy was associated with better BCSS rates, with 10-year BCSS rates of 97.6 and 94.5% in patients with and without postoperative radiotherapy, respectively (log-rank test, P = 0.001). Multivariate Cox proportional analysis indicated that receiving postoperative radiotherapy was an independent factor associated with better BCSS before (P < 0.001) and after PSM (P = 0.001), relative to those not receiving postoperative radiotherapy. Conclusions This study shows a decreasing utilization of postoperative radiotherapy following BCS of elderly PMBC patients over time. However, postoperative radiotherapy following BCS should be administered for elderly women with PMBC owing to independent association with better survival.
Aims To determine the biological correlation between apparent diffusion coefficient (ADC) values and Sirtuin1 (SIRT1) levels of tumour tissues in patients with esophageal carcinoma (EC), and to ascertain the treatment biomarker of ADC in predicting the early response of patients undergoing definitive chemoradiotherapy (CRT). Methods A total of 66 patients were enrolled, and the specimens of tumour tissues were collected before treatment to perform immunohistochemical (IHC) examinations and quantify the levels of SIRT1. Then all patients were given two esophageal magnetic resonance imaging (MRI) examinations with diffused weighed imaging (DWI) including pretreatment and intra-treatment (1 similar to 2 weeks after the start of radiotherapy). The regions of interest (ROIs) were contoured according to the stipulated rules in advance using off-line software, and the values of the ADC in the ROIs were generated automatically. Then, the values of the ADC at baseline and intra-treatment were labeled as pre-ADC and intra-ADC respectively, and Delta ADC, ADC(ratio) were calculated. Pearson's correlation coefficients were acquired to estimate the correlation between each of ADC values and SIRT1 levels. Spearman's rank correlation coefficients were acquired to estimate the correlation between early response and the values of each ADC. Receptor operation characteristics (ROC) curves were constructed to estimate the accuracy of the ADC in predicting the early response of CRT. Results The findings of this study showed different correlations between ADC values and the levels of SIRT1 (Delta ADC: r = - 0.943, P = 0.002; ADC(ratio): r = - 0.911, P = 0.000; intra-ADC: r = - 0.748, P = 0.002; pre-ADC: r = 0.109, P = 0.558). There was a positive correlation between Delta ADC and early response to treatment (rho = 0.615, P = 0.023), and multivariable logistic regression revealed that Delta ADC was significantly associated with short-term response of CRT in esophageal carcinoma patients. Conclusions In summary, early increases in ADC may facilitate the predication of early CRT response in patients with esophageal squamous cell carcinoma (ESCC), which may be attributed to the different correlation between ADC changes and SIRT1 expression.
Background The optimal treatment for elderly patients with early-stage non-small cell lung cancer (NSCLC) remains inconclusive. Previous studies have shown that stereotactic body radiotherapy (SBRT) provides encouraging local control though higher incidence of toxicity in elderly than younger populations. The objective of this study was to compare the outcomes of SBRT and surgical treatment in elderly patients with clinical stage I-II NSCLC. Methods This retrospective analysis included 205 patients aged >= 70 years with clinical stage I NSCLC who underwent SBRT or surgery at Zhejiang Cancer Hospital (Hangzhou, China) from January 2012 to December 2017. A propensity score matching analysis was performed between the two groups. In addition, we compared outcomes and related toxicity in both study arms. Results Each group included 35 patients who met the inclusion criteria. Median follow-up was 50.1 (0.8-74.4) months for surgery and 35.5 (11.5-71.4) months for SBRT. The rate of cancer-specific survival was similar between the two treatment arms (p = 0.958). In patients who underwent surgery, the corresponding 3- and 5-year cancer-specific survival rates were 85.3 and 81.7%, respectively. In those who received radiotherapy, these rates were 91.3 and 74.9%, respectively. Moreover, the 3- and 5-year locoregional control in patients who underwent surgery were 90.0 and 80.0%, respectively. In those who received radiotherapy, these rates were 91.1 and 84.1%, respectively. Notably, the observed differences in progression-free survival were not statistically significant (p = 0.934). In the surgery group, grade 1-2 complications were observed in eleven patients (31%). One patient died due to perioperative infection within 30 days following surgery. There was no grade 3-5 toxicity observed in the SBRT group. Conclusions The outcomes of surgery and SBRT in elderly patients with early-stage NSCLC were similar.
Background The appropriate timing of radiotherapy (RT) for patients after radical prostatectomy (RP) with adverse pathological features (APFs) remains controversial. This systematic review was conducted to compare the efficacy of adjuvant radiotherapy (ART) and salvage radiotherapy (SRT). Methods PubMed, EMBASE, Web of Science and the Cochrane Library electronic databases were searched to retrieve the required. The hazard ratio (HR) and corresponding 95% confidence interval (CI) of overall survival (OS), biochemical recurrence-free survival (BRFS) and distant metastases-free survival (DMFS) were extracted. The survival benefits of ART with SRT (including early salvage radiotherapy (ESRT)) were analyzed. The process of the meta-analysis was performed with RevMan version 5.3. Results A total of fifteen retrospective studies were finally included in the final analysis including 5586 patients. The pooled analysis indicated that ART could achieve better control of prostate cancer and improve OS (p = 0.0006), BRFS (p < 0.0001) and DMFS (p < 0.0001), when compared to SRT. The subgroup analysis of the 5-year OS rate demonstrated that the ART group still had survival advantages compared to the SRT group (p = 0.0006). However, ART and SRT were comparable in 10-year OS rate (p = 0.07). ART had advantages over SRT in both 5-year (p = 0.0003) and 10-year BRFS (p = 0.0003). The subgroup analysis with different follow-up starting points from RP or RT was essentially consistent with the above results. The pooled analysis also showed that ART was superior to ESRT on OS (p = 0.008) and DMFS (p = 0.03), and comparable to ESRT on BRFS (p = 0.1). Conclusions According to this meta-analysis, ART could be served as a preferential treatment for patients with APFs after RP to improve prognosis. Certainly, high-quality, multicenter randomized controlled trials (RCTs) are expecting to confirm the outcomes of our meta-analysis in the future.
Objective To determine the prognostic effect of adjuvant radiation and clinicopathological variables in surgically treated patients with small cell carcinoma of the cervix (SCCC). Methods Clinical data of SCCC patients with International Federation of Gynaecology and Obstetrics (FIGO) stage I-II underwent radical surgery from May 2000 to August 2014 at Sun Yat-sen Memorial Hospital were retrospectively reviewed. Forty-three patients with SCCC were included to this study. Chi-square test or Fisher's exact test, Student's t test or Mann-Whitney U test, Kaplan-Meier method and multivariate analysis of Cox proportional hazards regression were used for statistical analysis. P < 0.05 was considered to be statistically significant. Results Among 43 patients (median age, 49 years old) recruited, 25(58.1%) had stage I, 18(41.9%) had stage II disease. The 5-year overall survival (OS) rate was 39.54%, and the 5-year disease free survival (DFS) was 27.91%. Distant metastasis was the main cause of treatment failure (71.9%). Patients with adjuvant chemoradiation displayed lower rate of local recurrence than those with adjuvant chemotherapy (10.7% vs 60.0%, P < 0.0001). Multivariable analysis identified lymph node metastasis as a significant prognostic factor for both DFS and OS (P = 0.001, 0.004 respectively). Age was also an independent predictor of OS (P = 0.004). Adjuvant radiation appeared to significantly improve DFS (HR = 0.383, 95% CI, 0.185-0.791), but not OS. Conclusions Adjuvant radiotherapy could improve the local control and prolong DFS in surgically treated SCCC. However, a large prospective clinical trial is needed to confirm this.
BackgroundRadiation caries is a complication of radiotherapy characterized by enamel erosion and dentin exposure. The mechanisms of characteristic radiation caries formation are not well-understood. The aim of this study was to evaluate the direct radiation-induced effects on dental hard tissue and investigate their role in the formation of radiation caries.MethodsSixty non-carious third molars were divided into three groups (n=20), which would be exposed to 0Gy, 30Gy, and 60Gy radiation, respectively. After radiation, microhardness and elastic modulus were measured at four depths by means of a Vickers microhardness tester and atomic force microscopy (AFM). The microstructure was observed by scanning electron microscopy (SEM). X-ray diffraction and Raman microspectroscopy were used to determine crystal properties and protein/mineral (2931/960cm(-1)) ratios.ResultsA statistically significant decrease in microhardness and elastic modulus values 50m from the dentino-enamel junction (DEJ) in enamel was revealed in the 30-Gy and 60-Gy groups. With the increasing dose, destruction of interprismatic substance and fissures at the DEJ-adjacent region were found. A greater reduction of crystallinity was revealed in enamel compared with dentin. Raman spectroscopic analysis showed a slight increase of the protein/mineral ratio for enamel following accumulated radiation, while the protein/mineral ratio for dentin was decreased.ConclusionsRadiation could directly alter the mechanical properties, micro-morphology, crystal properties, and chemical composition of dental hard tissue. The early destruction of DEJ-adjacent enamel, combined with decreased crystallinity of enamel under radiation exposure, may be related to the formation of characteristic radiation caries.
BackgroundThe optimal care for pT3N0 rectal cancer remains controversial. And whether tumor location can be used to guide the administration of adjuvant radiotherapy for pT3N0 rectal cancer is not fully confirmed. The current study was designed to identify the benefit of adjuvant radiotherapy for pT3N0 rectal cancer.MethodsWe performed a retrospective study of 265 pT3N0 rectal cancer patients who were treated by surgery and adjuvant therapy from Mar. 2005 to Sept. 2015. All patients were divided into two groups according to receiving adjuvant radiotherapy or not. Overall survival (OS), disease-free survival (DFS) were compare between patients who did and did not receive adjuvant radiotherapy. Multivariate analysis was performed to explore clinical factors significantly associated with DFS, local recurrence-free survival (LRFS) and distant metastasis-free survival (DMFS).ResultsFor patients with lower tumor, DFS in adjuvant chemo-radiotherapy group was higher than that in adjuvant chemotherapy group. Besides, the rates of local recurrence and distant metastasis were found lower in patients who did receive adjuvant radiotherapy than those who did not. For patients with upper tumor, the 5-year OS and DFS were similar between groups of adjuvant chemotherapy and adjuvant chemo-radiotherapy. Multivariable analysis indicated both the CEA and tumor location were independent predictors of LRFS. And adjuvant radiotherapy predicted the DFS, LRFS and DMFS in lower rectal cancer patients.ConclusionTumor location can serve as an indication for the administration of adjuvant radiotherapy in pT3N0 rectal cancer patients.
ObjectivesInduction chemotherapy (IC) now is gaining recognition for the treatment of nasopharyngeal carcinoma (NPC). The current study was conducted to examine the association between prognosis and the interval between IC and radiotherapy (RT) in NPC patients.MethodsPatients with newly diagnosed, non-metastatic NPC who were treated with IC followed by RT from 2009 to 2012 were identified from an inpatient database. Overall survival (OS), disease-free survival (DFS), distant metastasis-free survival (DMFS) and locoregional recurrence-free survival (LRFS) were compared between those with interval30 and>30days by Kaplan-Meier and log-rank analyses; Cox modeling was used for multivariable analysis.ResultsA total of 668 patients met inclusion criteria with median follow-up of 64.4months. Patients were categorized by interval: 608 patients with interval30days, and 60 with interval>30days. The 5-year OS, DFS, DMFS and LRFS rates were 86.6, 78.2, 88.0 and 89.8% for patients with interval30days, respectively, and 69.2, 64.5, 71.2 and 85.1% for patients with interval>30days, respectively. The prolonged interval was a risk factor for OS, DFS and DMFS with adjusted hazard ratios (95% confidence intervals) were 2.44 (1.48-4.01), 1.99 (1.27-3.11) and 2.62 (1.54-4.47), respectively.ConclusionsProlonged interval>30days was associated with a significantly higher risk of distant metastasis and death in NPC patients. Efforts should be made to avoid prolonged interval between IC and RT to minimize the risk of treatment failure.
BackgroundThe aim of this study is to evaluate the prognostic value of grading MRI-detected skull-base invasion in nasopharyngeal carcinoma (NPC) with skull-base invasion after intensity-modulated radiotherapy (IMRT).MethodsThis study is a retrospective chart review of 469 non-metastatic NPC patients with skull-base invasion. Patients were classified as extensive skull-base invasion (ESBI) group and limited skull-base invasion (LSBI) group.ResultsMultivariate analysis showed that the skull-base invasion (LSBI vs. ESBI) was an independent prognostic predictor of progression free survival (PFS). The estimated 5-year local failure free survival (LFFS), distant metastasis free survival (DMFS), PFS, and overall survival (OS) rates for patients in the T3-LSBI and T3-ESBI group were 92.9% versus 93.5, 89.8% versus 86.1, 81.6% versus 76.4, and 93.5% versus 86.3%, respectively (P>0.05).ConclusionGrading of MRI-detected skull-base invasion is an independent prognostic factor of NPC with skull-base invasion. It is scientific and reasonable for skull-base invasion as a single entity to be classified as T3 classification.
BackgroundTo evaluate the safety and efficacy of particle therapy (PT) using pencil beam scanning (PBS) technique for early stage non-small cell lung cancer (NSCLC).MethodsFrom 08/2014 to 03/2018, 31 consecutive patients with sum of the longest diameters of primary tumor and hilar lymph node <5cm, N0-1, M0 NSCLC treated with PT were retrospectively analyzed. Gating/active breathing control techniques were used to control tumor motion in 20 and 7 patients. PBS-based proton radiotherapy (PRT) or carbon ion radiotherapy (CIRT) plans were designed via Syngo (R) planningsystem. PRT, PRT+CIRT boost, and CIRT were used in 6, 6 and 19 patients, respectively. Prescriptions were categorized to 3 levels: 5-7.5 GyE * 8-10 Fx, 4-5 GyE * 15-16 Fx and 2.25-3.5 GyE * 20-31 Fx.ResultsThirty-one patients (20 males and 11 females) with a median age of 71 (50-80) years were enrolled with a median follow-up time of 12.1 (2.9-45.2) months. Fourteen were adenocarcinomas, 7 squamous cell carcinomas, 4 non-specified NSCLC and 6 had no histological diagnosis (4/6 had previous resected lung cancer). The median tumor size was 3.1 (1.1-4.7) cm. No grade 4-5 toxicities were observed. One patient experienced grade 3 (per the Common Terminology Criteria for Adverse Events version 4.03) radiation-induced lung injury (RILI) at 6.7months from radiation started. Grade 2 acute toxicities included hematological toxicities (5 cases), RILI (2), plural pain (1) and dermatitis (1). Grade 2 late toxicities included RILI (3) and asymptomatic rib fracture (1). Three patients had progressed disease at 4.0 similar to 10.6months after the initiation of PT. One experienced local failure withsimultaneous distant failure and died of brain metastasis at 10.8months; one developed regional and distant failure and died of lung infection at 8.7months; the other experienced isolated distant failure only and his disease was well controlled after salvage systemic therapy. The estimated rates of progression-free survival, local control, cause-specific survival and overall survival at 1, 2years were 85.5% and 85.5%, 95.2% and 95.2%, 95.0% and 95.0%, 90.7% and 90.7%, respectively.ConclusionsPBS-based PT appears safe and effective for early stage NSCLC. Further follow-up and investigation is warranted.Trial registrationISRCTN, ISRCTN78973763. Registered 14 August 2018- Retrospectively registered, http://www.isrctn.com/ISRCTN78973763.
BackgroundThree-dimensional ultrasound (3DUS) is an attractive option in image-guided radiotherapy (IGRT) for prostate cancer (PCa) patients. However, the potential factors influencing the accuracy of 3DUS in comparison with cone-beam CT (CBCT) in IGRT for PCa patients haven't been clearly identified.MethodsThe differences between US/US and CBCT/CT registrations were analyzed over 586 and 580 sessions for 24 and 25 PCa patients treated with or without pelvic lymph node irradiation, respectively. The clinical factors that may influence registration differences were also evaluated.ResultsThe average discrepancies between US/US and CBCT/CT registrations were-0.285.28mm, -0.16 +/- 3.48mm, and-0.47 +/- 4.31mm in the superior-inferior (SI), left-right (LR), and anterior-posterior (AP) directions, respectively. The discrepancies were respectively less than 5mm longitudinally, laterally, and vertically in 64.4 and 70.1%, 84.9 and 89.2%, and 75.9 and 79.1% of the patients treated with or without pelvic lymph node irradiation, respectively. The registration differences were significantly smaller at least in one direction in patients younger than 70years, without pelvic lymph node irradiation, guided by transperineal ultrasonography and had a bladder volume smaller than 300mL.Conclusions p id=Par4 Age, irradiated regions, 3DUS modality, and bladder volume are important factors that may influence the differences between US/US and CBCT/CT registrations. 3DUS guidance is more feasible for younger PCa patients with a better control of bladder volume during the treatment and those who did not undergo pelvic lymph node irradiation.
ObjectiveThis study aimed to evaluate the role of postoperative radiotherapy (RT) in dermatofibrosarcoma protuberans (DFSP) and identify the prognostic factors influencing the disease-free survival (DFS).MethodsA total of 184 patients with DFSP were analyzed from 2000 to 2016. The regression model was used to examine the prognostic factors for DFS. Baseline covariates were balanced using a propensity score model. The role of RT was assessed by comparing the DFS of the surgery + RT group with that of the surgery group.ResultsThe median follow-up was 58months (range, 6-203months). The 5-year DFS rate was 89.8%. The univariate analysis showed that age50years, presence of fibrosarcoma, margins <2cm, and tumor size 5cm were associated with worse DFS (P=0.002, P<0.001, P=0.030, and P=0.032, respectively). The multivariate Cox regression model revealed that age, margin width, lesion number, and histological subtype independently affected DFS. The Ki-67 expression was related to age and histological subtype. Patients with Ki-6717% showed a worse DFS than those with Ki-67<17% (35.8% vs 87.8%, P=0.002). In the matched cohort, DFS was significantly higher in the S+RT group than in the S group (5-year DFS, 88.1% vs 56.2%, P=0.044).ConclusionsAge, margin width, lesion number, and histological subtype were independent risk factors for DFS in patients with DFSP. The high expression of Ki-67 could predict a poor prognosis. Postoperative RT could improve DFS for patients with DFSP.
BackgroundIn patients with T4 nasopharyngeal carcinoma (NPC), death may occur prior to the occurrence of temporal lobe injury (TLI). Because such competing risk death precludes the occurrence of TLI and thus the competing risk analysis should be applied to TLI research. The aim was to investigate the incidence and predictive factors of TLI after intensity-modulated radiotherapy (IMRT) among T4 NPC patients.MethodsFrom March 2008 to December 2014, T4 NPC patients treated with full-course radical IMRT at our center were reviewed retrospectively. A nested case-control study was designed for this cohort of patients. The cases were patients with TLI diagnosed by MRI during the follow-up period, and the controls were patients without TLI after IMRT matched 1:1 to each case by gender, age at diagnosis, intercranial involvement, and follow-up time. The end point was time to TLI or death without prior TLI. We analyzed the cumulative incidence function (CIF) and performed a competing risk regression model to identify the predictors of TLI.ResultsWith a median follow-up of 40.1months, 63 patients (63/506, 12.5%) developed TLI as diagnosed by MRI, and 136 deaths occurred during the period. The cumulative incidence of TLI at 5years was 13.2%, while 26.7% died without prior TLI. The univariate analysis showed that all selected dosimetric parameters were associated with the occurrence of TLI. On multivariate analysis, D1cc and V20 remained statistically significant. Based on the area-under-the-curve (AUC) values, D1cc was considered the most predictive. The patients with D1cc >71.14Gy had a 7.920-fold increased risk of TLI compared with those with D1cc 71.14Gy (P<0.05). Similarly, V20>42.22cc was found to result in a statistically significant higher risk of TLI (subdistribution hazard ratio [sHR] =3.123, P<0.05).ConclusionsTL D1cc and V20 were predictive of TLI after IMRT for T4 NPC. They should be considered as first and second priorities of dose constraints of the TL. D1cc 71.14Gy and V2042.22cc could be useful dose-volume constraints for reducing the occurrence of TLI during IMRT treatment planning without obviously compromising the tumor coverage.