A Combined Model to Improve the Prediction of Local Control for Lung Cancer Patients Undergoing Stereotactic Body Radiotherapy Based on Radiomic Signature Plus Clinical and Dosimetric Parameters.

PURPOSE: Stereotactic body radiotherapy (SBRT) is an important treatment modality for lung cancer patients, however, tumor local recurrence rate remains some challenge and there is no reliable prediction tool. This study aims to develop a prediction model of local control for lung cancer patients undergoing SBRT based on radiomics signature combining with clinical and dosimetric parameters. METHODS: The radiomics model, clinical model and combined model were developed by radiomics features, incorporating clinical and dosimetric parameters and radiomics signatures plus clinical and dosimetric parameters, respectively. Three models were established by logistic regression (LR), decision tree (DT) or support vector machine (SVM). The performance of models was assessed by receiver operating characteristic curve (ROC) and DeLong test. Furthermore, a nomogram was built and was assessed by calibration curve, Hosmer-Lemeshow and decision curve. RESULTS: The LR method was selected for model establishment. The radiomics model, clinical model and combined model showed favorite performance and calibration (Area under the ROC curve (AUC) 0.811, 0.845 and 0.911 in the training group, 0.702, 0.786 and 0.818 in the validation group, respectively). The performance of combined model was significantly superior than the other two models. In addition, Calibration curve and Hosmer-Lemeshow (training group: P = 0.898, validation group: P = 0.891) showed good calibration of combined nomogram and decision curve proved its clinical utility. CONCLUSIONS: The combined model based on radiomics features plus clinical and dosimetric parameters can improve the prediction of 1-year local control for lung cancer patients undergoing SBRT.

Radiobiological evaluation of simultaneously dose-escalated versus non-escalated intensity-modulated radiation therapy for patients with upper thoracic esophageal cancer.

OBJECTIVE: To compare the radiobiological response between simultaneously dose-escalated and non-escalated intensity-modulated radiation therapy (DE-IMRT and NE-IMRT) for patients with upper thoracic esophageal cancer (UTEC) using radiobiological evaluation. METHODS: Computed tomography simulation data sets for 25 patients pathologically diagnosed with primary UTEC were used in this study. DE-IMRT plan with an escalated dose of 64.8 Gy/28 fractions to the gross tumor volume (GTV) and involved lymph nodes from 25 patients pathologically diagnosed with primary UTEC, was compared to an NE-IMRT plan of 50.4 Gy/28 fractions. Dose-volume metrics, tumor control probability (TCP), and normal tissue complication probability for the lung and spinal cord were compared. In addition, the risk of acute esophageal toxicity (AET) and late esophageal toxicity (LET) were also analyzed. RESULTS: Compared with NE-IMRT plan, we found the DE-IMRT plan resulted in a 14.6 Gy dose escalation to the GTV. The tumor control was predicted to increase by 31.8%, 39.1%, and 40.9% for three independent TCP models. The predicted incidence of radiation pneumonitis was similar (3.9% versus 3.6%), and the estimated risk of radiation-induced spinal cord injury was extremely low (<0.13%) in both groups. Regarding the esophageal toxicities, the estimated grade ≥2 and grade ≥3 AET predicted by the Kwint model were increased by 2.5% and 3.8%. Grade ≥2 AET predicted using the Wijsman model was increased by 14.9%. The predicted incidence of LET was low (<0.51%) in both groups. CONCLUSION: Radiobiological evaluation reveals that the DE-IMRT dosing strategy is feasible for patients with UTEC, with significant gains in tumor control and minor or clinically acceptable increases in radiation-induced toxicities.

Different definitions of esophagus influence esophageal toxicity prediction for esophageal cancer patients administered simultaneous integrated boost versus standard-dose radiation therapy.

We aim to evaluate whether different definitions of esophagus (DEs) impact on the esophageal toxicity prediction for esophageal cancer (EC) patients administered intensity-modulated radiation therapy with simultaneous integrated boost (SIB-IMRT) vs. standard-dose IMRT (SD-IMRT). The esophagus for 21 patients diagnosed with primary EC were defined in the following four ways: the whole esophagus, including the tumor (ESOwhole); ESOwhole within the treatment field (ESOinfield); ESOinfield, excluding the tumor (ESOinfield-tumor) and ESOwhole, excluding the tumor (ESOwhole-tumor). The difference in the dose variation, acute esophageal toxicity (AET) and late esophageal toxicity (LET) of four DEs were compared. We found that the mean esophageal dose for ESOwhole, ESOinfield, ESOinfield-tumor and ESOwhole-tumor were increased by 7.2 Gy, 10.9 Gy, 4.6 Gy and 2.0 Gy, respectively, in the SIB-IMRT plans. Radiobiological models indicated that a grade ≥ 2 AET was 2.9%, 3.1%, 2.2% and 1.6% higher on average with the Kwint model and 14.6%, 13.2%, 7.2% and 3.4% higher with the Wijsman model for the four DEs. A grade ≥ 3 AET increased by 4.3%, 7.2%, 4.2% and 1.2%, respectively. Additionally, the predicted LET increased by 0.15%, 0.39%, 1.2 × 10-2% and 1.5 × 10-3%. Our study demonstrates that different DEs influence the esophageal toxicity prediction for EC patients administered SIB-IMRT vs. SD-IMRT treatment.

A Dosimetric Study of Using Fixed-Jaw Volumetric Modulated Arc Therapy for the Treatment of Nasopharyngeal Carcinoma with Cervical Lymph Node Metastasis.

PURPOSE: To study the dosimetric difference between fixed-jaw volumetric modulated radiotherapy (FJ-VMAT) and large-field volumetric modulated radiotherapy (LF-VMAT) for nasopharyngeal carcinoma (NPC) with cervical lymph node metastasis. METHODS: Computed tomography (CT) datasets of 10 NPC patients undergoing chemoradiotherapy were used to generate LF-VMAT and FJ-VMAT plans in the Eclipse version 10.0 treatment planning system. These two kinds of plans were then compared with respect to planning-target-volume (PTV) coverage, conformity index (CI), homogeneity index (HI), organ-at-risk sparing, monitor units (MUs) and treatment time (TT). RESULTS: The FJ-VMAT plans provided lower D2% of PGTVnd (PTV of lymph nodes), PTV1 (high-risk PTV) and PTV2 (low-risk PTV) than did the LF-VMAT plans, whereas no significant differences were observed in PGTVnx (PTV of primary nasopharyngeal tumor). The FJ-VMAT plans provided lower doses delivered to the planning organ at risk (OAR) volumes (PRVs) of both brainstem and spinal cord, both parotid glands and normal tissue than did the LF-VMAT plans, whereas no significant differences were observed with respect to the oral cavity and larynx. The MUs of the FJ-VMAT plans (683 ± 87) were increased by 22% ± 12% compared with the LF-VMAT plans (559 ± 62). In terms of the TT, no significant difference was found between the two kinds of plans. CONCLUSIONS: FJ-VMAT was similar or slightly superior to LF-VMAT in terms of PTV coverage and was significantly superior in terms of OAR sparing, at the expense of increased MUs.

Radiobiological modeling of two stereotactic body radiotherapy schedules in patients with stage I peripheral non-small cell lung cancer.

This study aims to compare the radiobiological response of two stereotactic body radiotherapy (SBRT) schedules for patients with stage I peripheral non-small cell lung cancer (NSCLC) using radiobiological modeling methods. Volumetric modulated arc therapy (VMAT)-based SBRT plans were designed using two dose schedules of 1 × 34 Gy (34 Gy in 1 fraction) and 4 × 12 Gy (48 Gy in 4 fractions) for 19 patients diagnosed with primary stage I NSCLC. Dose to the gross target volume (GTV), planning target volume (PTV), lung and chest wall (CW) were converted to biologically equivalent dose in 2 Gy fraction (EQD2) for comparison. Five different radiobiological models were employed to predict the tumor control probability (TCP) value. Three additional models were utilized to estimate the normal tissue complication probability (NTCP) value for the lung and the modified equivalent uniform dose (mEUD) value to the CW. Our result indicates that the 1 × 34 Gy dose schedule provided a higher EQD2 dose to the tumor, lung and CW. Radiobiological modeling revealed that the TCP value for the tumor, NTCP value for the lung and mEUD value for the CW were 7.4% (in absolute value), 7.2% (in absolute value) and 71.8% (in relative value) higher on average, respectively, using the 1 × 34 Gy dose schedule.

Monitor unit optimization in stereotactic body radiotherapy for small peripheral non-small cell lung cancer patients.

The increasingly attractive stereotactic body radiotherapy (SBRT) treatment for stage I lung cancer is concomitant with a large amount of monitor units (MU), leading to excessive out-of-field dose and prolonged beam-on time. The study aims to reduce the MU number and shorten the beam-on time by optimizing the planning parameters. Clinically acceptable treatment plans from fourteen patients suffered from peripheral stage I non-small cell lung cancer (NSCLC) were created in the study. Priority for the upper objective of the target (PUOT), strength and Max MU setting in the MU objective function (MUOF) were adjusted respectively to investigate their effect on MU number, organs at risk (OARs) sparing and beam-on time. We found that the planning parameters influenced the MU number in a PUOT, strength and Max MU dependent manner. Combined with high priority for the UOT (HPUOT) and MUOF, the MU number was reduced from 443 ± 25 to 228 ± 22 MU/Gy without compromising the target coverage and OARs sparing. We also found beam-on time was proportional to MU number and it could be shortened from 7.9 ± 0.5 to 4.1 ± 0.4 minutes.

Radiobiological modeling analysis of the optimal fraction scheme in patients with peripheral non-small cell lung cancer undergoing stereotactic body radiotherapy.

This study aimed to determine the optimal fraction scheme (FS) in patients with small peripheral non-small cell lung cancer (NSCLC) undergoing stereotactic body radiotherapy (SBRT) with the 4 × 12 Gy scheme as the reference. CT simulation data for sixteen patients diagnosed with primary NSCLC or metastatic tumor with a single peripheral lesion ≤3 cm were used in this study. Volumetric modulated arc therapy (VMAT) plans were designed based on ten different FS of 1 × 25 Gy, 1 × 30 Gy, 1 × 34 Gy, 3 × 15 Gy, 3 × 18 Gy, 3 × 20 Gy, 4 × 12 Gy, 5 × 12 Gy, 6 × 10 Gy and 10 × 7 Gy. Five different radiobiological models were employed to predict the tumor control probability (TCP) value. Three other models were utilized to estimate the normal tissue complication probability (NTCP) value to the lung and the modified equivalent uniform dose (mEUD) value to the chest wall (CW). The 1 × 30 Gy regimen is recommended to achieve 4.2% higher TCP and slightly higher NTCP and mEUD values to the lung and CW compared with the 4 × 12 Gy schedule, respectively. This regimen also greatly shortens the treatment duration. However, the 3 × 15 Gy schedule is suggested in patients where the lung-to-tumor volume ratio is small or where the tumor is adjacent to the CW.

Comparison of Two RapidArc Delivery Strategies in Stereotactic Body Radiotherapy of Peripheral Lung Cancer with Flattening Filter Free Beams.

PURPOSE: To investigate the performance of using partial arc (PA) and full arc with avoidance sectors (FAAS) in stereotactic body radiotherapy (SBRT) of peripheral lung cancer with flattening filter free (FFF) beams. METHODS: Eighteen patients with primary (T1 or T2) non-small-cell lung cancer (NSCLC) or lung metastatic were selected for this study. Nine patients with a gross tumor volume (GTV) <= 10 cc were designated as the small tumor group. The other nine patients with a GTV between 10 cc and 44 cc were assigned to the large tumor group. The treatment plans were generated in eighteen patients using PA and FAAS techniques, respectively, and delivered with a Varian TrueBeam Linac. Dosimetry of the target and organs at risk (OARs), monitor unit (MU), out-of-field dose, and delivery time were statistically analyzed. Delta4 and portal dosimetry were employed to evaluate the delivery accuracy. RESULTS: For the small tumor group, compared with the PA plans, the FAAS plans significantly achieved a lower MU/fraction, out-of-field dose and a shorter treatment time (p<0.05), but the target dose was slightly higher than that delivered by PA plans (p<0.05). For the large tumor group, the PA plans significantly attained a shorter treatment time (p<0.05), whereas MU/fraction, out-of-field dose and dose to OARs were comparable between the two plans (p>0.05). Furthermore, all plans generated from the eighteen patients achieved a high pass rate in patient-specific quality assurance, with all the gamma indices greater than 97% at the Γ3mm, 3% threshold. CONCLUSION: This study suggests that the FAAS technique is more beneficial for the small tumor patients undergoing lung SBRT with FFF beams because of its higher treatment efficiency and MU reduction. However, for the large tumor patients, the PA technique is recommended due to its higher treatment efficiency.

Volumetric modulated arc therapy vs. c-IMRT for the treatment of upper thoracic esophageal cancer.

OBJECTIVE: To compare plans using volumetric-modulated arc therapy (VMAT) with conventional sliding window intensity-modulated radiation therapy (c-IMRT) to treat upper thoracic esophageal cancer (EC). METHODS: CT datasets of 11 patients with upper thoracic EC were identified. Four plans were generated for each patient: c-IMRT with 5 fields (5F) and VMAT with a single arc (1A), two arcs (2A), or three arcs (3A). The prescribed doses were 64 Gy/32 F for the primary tumor (PTV64). The dose-volume histogram data, the number of monitoring units (MUs) and the treatment time (TT) for the different plans were compared. RESULTS: All of the plans generated similar dose distributions for PTVs and organs at risk (OARs), except that the 2A- and 3A-VMAT plans yielded a significantly higher conformity index (CI) than the c-IMRT plan. The CI of the PTV64 was improved by increasing the number of arcs in the VMAT plans. The maximum spinal cord dose and the planning risk volume of the spinal cord dose for the two techniques were similar. The 2A- and 3A-VMAT plans yielded lower mean lung doses and heart V50 values than the c-IMRT. The V20 and V30 for the lungs in all of the VMAT plans were lower than those in the c-IMRT plan, at the expense of increasing V5, V10 and V13. The VMAT plan resulted in significant reductions in MUs and TT. CONCLUSION: The 2A-VMAT plan appeared to spare the lungs from moderate-dose irradiation most effectively of all plans, at the expense of increasing the low-dose irradiation volume, and also significantly reduced the number of required MUs and the TT. The CI of the PTVs and the OARs was improved by increasing the arc-number from 1 to 2; however, no significant improvement was observed using the 3A-VMAT, except for an increase in the TT.

Simultaneous modulated accelerated radiation therapy for esophageal cancer: a feasibility study.

AIM: To establish the feasibility of simultaneous modulated accelerated radiation therapy (SMART) in esophageal cancer (EC). METHODS: Computed tomography (CT) datasets of 10 patients with upper or middle thoracic squamous cell EC undergoing chemoradiotherapy were used to generate SMART, conventionally-fractionated three-dimensional conformal radiotherapy (3DCRT) and intensity-modulated radiation therapy (cf-IMRT) plans, respectively. The gross target volume (GTV) of the esophagus, positive regional lymph nodes (LN), and suspected lymph nodes (LN ±) were contoured for each patient. The clinical target volume (CTV) was delineated with 2-cm longitudinal and 0.5- to 1.0-cm radial margins with respect to the GTV and with 0.5-cm uniform margins for LN and LN(±). For the SMART plans, there were two planning target volumes (PTVs): PTV66 = (GTV + LN) + 0.5 cm and PTV54 = CTV + 0.5 cm. For the 3DCRT and cf-IMRT plans, there was only a single PTV: PTV60 = CTV + 0.5 cm. The prescribed dose for the SMART plans was 66 Gy/30 F to PTV66 and 54 Gy/30 F to PTV54. The dose prescription to the PTV60 for both the 3DCRT and cf-IMRT plans was set to 60 Gy/30 F. All the plans were generated on the Eclipse 10.0 treatment planning system. Fulfillment of the dose criteria for the PTVs received the highest priority, followed by the spinal cord, heart, and lungs. The dose-volume histograms were compared. RESULTS: Clinically acceptable plans were achieved for all the SMART, cf-IMRT, and 3DCRT plans. Compared with the 3DCRT plans, the SMART plans increased the dose delivered to the primary tumor (66 Gy vs 60 Gy), with improved sparing of normal tissues in all patients. The Dmax of the spinal cord, V20 of the lungs, and Dmean and V50 of the heart for the SMART and 3DCRT plans were as follows: 38.5 ± 2.0 vs 44.7 ± 0.8 (P = 0.002), 17.1 ± 4.0 vs 25.8 ± 5.0 (P = 0.000), 14.4 ± 7.5 vs 21.4 ± 11.1 (P = 0.000), and 4.9 ± 3.4 vs 12.9 ± 7.6 (P = 0.000), respectively. In contrast to the cf-IMRT plans, the SMART plans permitted a simultaneous dose escalation (6 Gy) to the primary tumor while demonstrating a significant trend of a lower irradiation dose to all organs at risk except the spinal cord, for which no significant difference was found. CONCLUSION: SMART offers the potential for a 6 Gy simultaneous escalation in the irradiation dose delivered to the primary tumor of EC and improves the sparing of normal tissues.

Long-term outcomes and prognostic factors for patients with esophageal cancer following radiotherapy.

AIM: To evaluate long-term outcomes and prognostic factors for esophageal squamous cell carcinoma (SCC) treated with three dimensional conformal radiotherapy (3D-CRT). METHODS: Between January 2005 and December 2006, 153 patients (120 males, 33 females) with pathologically confirmed esophageal SCC and treated with 3D-CRT in Cancer Hospital of Shantou University were included in this retrospective analysis. Median age was 60 years (range: 37-84 years). The proportion of tumor location was as follows: upper thorax (including the cervical region), 73 (48%); middle thorax, 73 (48%); lower thorax, 7 (5%), respectively. The median radiation dose was 64 Gy (range: 50-74 Gy). Fifty four cases (35%) received cisplatin-based concurrent chemotherapy. Univariate and multivariate analysis were performed to determine the association between the correlative factors and prognosis. RESULTS: The five-year overall survival rate was 26.3%, with a median follow-up of 49 mo (range: 3-66 mo) for patients who were still alive. On univariate analysis, lesion location, lesion length by barium esophagogram, computed tomography imaging characteristics including Y diameter (anterior-posterior, AP, extent of tumor), gross tumor volume of primary lesion (GTV-E), volume of positive lymph nodes (GTV-LN), and the total target volume (GTV-T = GTV-E + GTV-LN) were prognostic for overall survival. By multivariate analysis, only the Y diameter [hazard ratio (HR) 2.219, 95%CI 1.141-4.316, P = 0.019] and the GTV-T (HR 1.372, 95%CI 1.044-1.803, P = 0.023) were independent prognostic factors for survival. CONCLUSION: The overall survival of esophageal carcinoma patients undergoing 3D-CRT was promising. The best predictors for survival were GTV-T and Y diameter.

Long term outcomes and prognostic factors of n0 stage nasopharyngeal carcinoma: a single institutional experience with 610 patients.

Treatment responses of N0 stage nasopharyngeal carcinoma were firstly analyzed comprehensively to evaluate long term outcomes of patients and identify prognostic factors. A total of 610 patients with N0 NPC, undergoing definitive radiotherapy to their primary lesion and prophylactic radiation to upper neck, were reviewed retrospectively. Concomitant chemotherapy was administrated to 65 out of the 610. Survival rates of the patients were calculated using the Kaplan-Meier method and compared by log-rank test. Prognostic factors were identified by the Cox regression model. The study revealed the 5-year and 10-year overall, disease-free, disease-specific, local failure-free, regional failure-free, locoregional failure-free and distant metastasis-free survival rates to be 78.7% and 66.8%, 68.8% and 55.8%, 79.9% and 70.4%, 81.2% and 72.5%, 95.8% and 91.8%, 78.3% and 68.5%, 88.5% and 85.5%, respectively. There were 192 patients experiencing failure (31.5%) after radiotherapy or chemoradiotherapy. Of these, local recurrence, regional relapse and distant metastases as the first event of failure occurred in 100 (100/610, 16.4%), 15(15/610, 2.5%) and 52 (52/610, 8.5%), respectively. Multivariate analysis showed that T stage was the only independent prognostic factor for patients with N0 NPC (P=0.000). Late T stage (P=0.000), male (P=0.039) and anemia (P=0.007) were independently unfavorable factors predicting disease-free survival. After treatment, satisfactory outcome wasgenerally achieved in patients with N0 NPC. Local recurrence represented the predominant mode of treatment failure, while T stage was the only independent prognostic factor for overall survival. Late T stage, male gender, and anemia independently predicted lower possibility of the disease-free survival.

[Dosimetric comparison between intensity-modulated radiotherapy and conformal radiotherapy for upper thoracic esophageal carcinoma].

BACKGROUND AND OBJECTIVE: Treatment planning for radiotherapy of upper thoracic esophageal carcinoma is challenging due to the anatomical features. The difficulty may be resolved by intensity-modulated radiotherapy (IMRT). This study was to compare the dosimetric advantages of IMRT to that of conformal radiotherapy (CRT) for upper thoracic esophageal carcinoma, and to explore the clinical application of IMRT. METHODS: Eleven patients with upper thoracic esophageal carcinoma were enrolled. In addition to the actually used CRT plan, a five-field IMRT plan was generated for each case. The parameters of dose volume histogram for targets and organs at risk were compared between two techniques. RESULTS: For the planning target volume (PTV) of tumor and para-tumor tissues, the mean dose, maximal dose, doses covering 99% and 95% volume were similar in IMRT and CRT plans (P>0.05). However, IMRT plan had a higher conformity index than CRT plan (0.68+/-0.04 vs. 0.46+/-0.11, P<0.01). For the PTV of supraclavicular region, IMRT plan showed a better dose heterogeneity index than CRT plan (1.17+/-0.05 vs. 1.33+/-0.15, P=0.01). IMRT plan had lower maximal dose to the planning risk volume of the spinal cord (44.4 Gy vs. 52.5 Gy, P<0.05) and lower lung volume received dose of 10 Gy or higher [(32+/-6)% vs. (35+/-9)%, P<0.05] than CRT plan. CONCLUSION: For the upper thoracic esophageal carcinoma, IMRT has more conformal distribution of dose and better spinal cord sparing than CRT, and can reduce the volume of lung that received dose of 10 Gy or higher.

[Long-term efficacy of prophylactic upper neck irradiation for stage N0 nasopharyngeal carcinoma].

BACKGROUND & OBJECTIVE: Whether prophylactic irradiation should cover the whole neck or just the upper neck for nasopharyngeal carcinoma (NPC) patients, without neck lymph node metastasis (N0), remains controversial. This study was to assess the rationality of prophylactic upper neck irradiation for stage N0 NPC patients. METHODS: Clinical data of 432 stage N0 NPC patients were analyzed. All patients were treated with radical radiotherapy alone. The extent of prophylactic irradiation was limited to the upper neck of the patients. Median radiation doses were 70 Gy for the primary tumors, and 50 Gy for the upper necks. Kaplan-Meier method was used to analyze survival rates and neck recurrence rates. Log-rank test was used to compare neck recurrence rates in patients with or without nasopharyngeal recurrence. Cox proportional hazards model was used to evaluate the prognostic factors for neck control. RESULTS: Seventeen out of 432 patients had neck recurrence. The 5-year control rate of the neck was 96.06%. Among the 17 patients with neck recurrence, 6 had concurrent nasopharyngeal relapse. The occurrence rates of neck recurrence alone were 0.93%(4/432) in the upper necks and 1.62% (7/432) in the lower necks (P=0.937). The neck recurrence rates were 9.52% (6/63) and 2.98% (11/369) in patients with and without nasopharyngeal recurrence, respectively (P=0.002). Nasopharyngeal recurrence was the only independent prognostic factor for neck control. CONCLUSION: The overall neck recurrence rate is low for stage N0 NPC patients after receiving irradiation. Prophylactic upper neck irradiation is reasonable for stage N0 NPC patients.