Comparison of Three Radiobiological Models in Stereotactic Body Radiotherapy for Non-Small Cell Lung Cancer.

Objective: The applicability of the linear quadratic (LQ) model to local control (LC) modeling after hypofractionated radiotherapy to treat lung cancer is highly debated. To date, the differences in predicted outcomes between the LQ model and other radiobiological models, which are characterized by additional dose modification beyond a certain transitional dose (dT), have not been well established. This study aims to compare the outcomes predicted by the LQ model with those predicted by two other radiobiological models in stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC). Methods: Computer tomography (CT) simulation data sets for 20 patients diagnosed with stage Ⅰ primary NSCLC were included in this study. Three radiobiological models, including the LQ, the universal survival curve (USC) and the modified linear quadratic and linear (mLQL) model were employed to predict the tumor control probability (TCP) data. First, the dT values for the USC and mLQL models were determined. Then, the biologically effective dose (BED) and the predicted TCP values from the LQ model were compared with those calculated from the USC and mLQL models. Results: The dT values from the USC model were 29.6 Gy, 33.8 Gy and 44.5 Gy, whereas the values were 90.2 Gy, 84.0 Gy and 57.3 Gy for the mLQL model for 1-year, 2-year and 3-year TCP prediction. The remarkable higher dT values obtained from the mLQL model revealed the same dose-response relationship as the LQ model in the low- and high-dose ranges. We also found that TCP prediction from the LQ and USC models differed by less than 3%, although the BED values for the two models were significantly different. Conclusion: Radiobiological analysis reveals small differences between the models and suggested that the LQ model is applicable for modeling LC using SBRT to treat lung cancer, even when an extremely high fractional dose is used.

Calculating the individualized fraction regime in stereotactic body radiotherapy for non-small cell lung cancer based on uncomplicated tumor control probability function.

BACKGROUND: To calculate the individualized fraction regime (IFR) in stereotactic body radiotherapy (SBRT) for non-small cell lung cancer (NSCLC) patients using the uncomplicated tumor control probability (UTCP, P+) function. METHODS: Thirty-three patients with peripheral lung cancer or lung metastases who had undergone SBRT were analyzed. Treatment planning was performed using the dose regime of 48 Gy in 4 fractions. Dose volume histogram (DVH) data for the gross tumor volume (GTV), lung, chest wall (CW) and rib were exported and the dose bin was multiplied by a certain percentage of the dose in that bin which ranged from 1 to 200% in steps of 1%. For each dose fraction, P+ values were calculated by considering the tumor control probability (TCP), radiation-induced pneumonitis (RIP), chest wall pain (CWP) and radiation-induced rib fracture (RIRF). UTCP values as a function of physical dose were plotted and the maximum P+ values corresponded to the optimal therapeutic gain. The IFR in 3 fractions was also calculated with the same method by converting the dose using the linear quadratic (LQ) model. RESULTS: Thirty-three patients attained an IFR using the introduced methods. All the patients achieved a TCP value higher than 92.0%. The IFR ranged from 3 × 10.8 Gy to 3 × 12.5 Gy for 3 fraction regimes and from 4 × 9.2 Gy to 4 × 10.7 Gy for 4 fraction regimes. Four patients with typical tumor characteristics demonstrated that the IFR was patient-specific and could maximize the therapeutic gain. Patients with a large tumor had a lower TCP and UTCP and a smaller fractional dose than patients with a small tumor. Patients with a tumor adjacent to the organ at risk (OAR) or at a high risk of RIP had a lower UTCP and a smaller fractional dose compared with patients with a tumor located distant from the OAR. CONCLUSIONS: The proposed method is capable of predicting the IFR for NSCLC patients undergoing SBRT. Further validation in clinical samples is required.

Comparative Analysis of Local Control Prediction Using Different Biophysical Models for Non-Small Cell Lung Cancer Patients Undergoing Stereotactic Body Radiotherapy.

PURPOSE: The consistency for predicting local control (LC) data using biophysical models for stereotactic body radiotherapy (SBRT) treatment of lung cancer is unclear. This study aims to compare the results calculated from different models using the treatment planning data. MATERIALS AND METHODS: Treatment plans were designed for 17 patients diagnosed with primary non-small cell lung cancer (NSCLC) using 5 different fraction schemes. The Martel model, Ohri model, and the Tai model were used to predict the 2-year LC value. The Gucken model, Santiago model, and the Tai model were employed to estimate the 3-year LC data. RESULTS: We found that the employed models resulted in completely different LC prediction except for the Gucken and the Santiago models which exhibited quite similar 3-year LC data. The predicted 2-year and 3-year LC values in different models were not only associated with the dose normalization but also associated with the employed fraction schemes. The greatest difference predicted by different models was up to 15.0%. CONCLUSIONS: Our results show that different biophysical models influence the LC prediction and the difference is not only correlated to the dose normalization but also correlated to the employed fraction schemes.

A dosimetric and treatment efficiency evaluation of stereotactic body radiation therapy for peripheral lung cancer using flattening filter free beams.

To investigate potential dosimetric benefits and treatment efficiency of dynamic conformal arc therapy (DCA), intensity modulated radiation therapy (IMRT), and double partial arcs Rapidarc (RA) techniques in the treatment of early-stage peripheral lung cancer using stereotactic body radiotherapy (SBRT) with flattening filter free (FFF) beams. Twenty early-stage peripheral lung cancer patients were selected. For each patient, DCA, IMRT and RA plans were created to meet Radiation Therapy Oncology Group (RTOG) 0915 objectives with 48 Gy covering 95% of the planning target volume (PTV) in 4 fractions. PTV coverage, organs at risk (OARs) doses, planning time, monitor units (MU) and treatment time were evaluated. RA was significantly better than DCA for PTV coverage. RA provided a lower V32Gy to chest wall and less V20Gy to lung over those of DCA and IMRT. For other OARs, there is no significant difference among all three techniques. DCA plans showed significantly less planning time, shorter treatment time and lower MU number than those of RA and IMRT. RA provides a superior dosimetric benefit to DCA and IMRT in the treatment of early-stage lung cancer using SBRT with FFF beams. Considering the MU number, planning time and treatment efficiency, DCA technique is an effective treatment strategy.

Effects of omitting elective neck irradiation to nodal Level IB in nasopharyngeal carcinoma patients with negative Level IB lymph nodes treated by intensity-modulated radiotherapy: a Phase 2 study.

OBJECTIVE: To investigate the need for elective neck irradiation (ENI) to nodal Level IB in patients with nasopharyngeal carcinoma (NPC) with negative Level IB lymph nodes (IB-negative) treated by intensity-modulated radiotherapy (IMRT). METHODS: We conducted a Phase 2 prospective study in 123 newly diagnosed IB-negative patients with NPC treated by IMRT, who met at least 1 of the following criteria: (1) unilateral or bilateral Level II involvement with 1 of the following: Level IIA involvement or any Level II node ≥2 cm/with extracapsular spread; (2) ≥2 unilateral node-positive regions. Bilateral Level IB nodes were not contoured as part of the treatment target and treated electively. Level IB regional recurrence rate; pattern of treatment failure; 3-year overall survival (3y-OS), 3-year local control (3y-LC) and 3-year regional control (3y-RC) rates; toxicities; and dosimetric data for planning target volumes, organs at risk, Level IB and submandibular glands (SMGs) were evaluated. RESULTS: Two patients developed failures at Level IB (1.6%). The 3y-LC, 3y-RC and 3y-OS rates were 93.5%, 93.5% and 78.0%, respectively. Bilateral Level IB received unplanned high-dose irradiation with a mean dose (Dmean) ≥50 Gy in 60% of patients. The average Dmean of bilateral SMGs was approximately 53 Gy. CONCLUSION: ENI to Level IB may be unnecessary in IB-negative patients with NPC treated by IMRT. A further Phase 3 study is warranted. ADVANCES IN KNOWLEDGE: Based on the results of this first Phase 2 study, we suggest omitting ENI to Level IB in Ib-negative patients with NPC with extensive nodal disease treated by IMRT.

Dosimetric analysis of isocentrically shielded volumetric modulated arc therapy for locally recurrent nasopharyngeal cancer.

This study aimed to investigate the dosimetric characteristics of an isocentrically shielded RapidArc (IS-RA) technique for treatment of locally recurrent nasopharyngeal cancer (lrNPC). In IS-RA, the isocenter was placed at the center of the pre-irradiated brainstem (BS)/spinal cord (SC) and the jaws were set to shield the BS/SC while ensuring the target coverage during the whole gantry rotation. For fifteen patients, the IS-RA plans were compared with the conventional RapidArc (C-RA) regarding target coverage, organ-at-risk (OAR) sparing and monitor units (MUs). The relationship between the dose reduction of BS/SC and some geometric parameters including the angle extended by the target with respect to the axis of BS/SC (Ang_BSSC), the minimum distance between the target and BS/SC (Dist_Min) and the target volume were evaluated. The IS-RA reduced the BS/SC doses by approximately 1-4 Gy on average over the C-RA, with more MUs. The IS-RA demonstrated similar target coverage and sparing of other OARs except for slightly improved sparing of optic structures. More dose reduction in the isocentric region was observed in the cases with larger Ang_BSSC or smaller Dist_Min. Our results indicated that the IS-RA significantly improves the sparing of BS/SC without compromising dosimetric requirements of other involved structures for lrNPC.

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.

Dosimetric evaluation of a simple planning method for improving intensity-modulated radiotherapy for stage III lung cancer.

This study aimed to evaluate the dosimetric outcomes of a base-dose-plan-compensation (BDPC) planning method for improving intensity-modulated radiotherapy (IMRT) for stage III lung cancer. For each of the thirteen included patients, three types of planning methods were applied to obtain clinically acceptable plans: (1) the conventional optimization method (CO); (2) a split-target optimization method (STO), in which the optimization objectives were set higher dose for the target with lung density; (3) the BDPC method, which compensated for the optimization-convergence error by further optimization based on the CO plan. The CO, STO and BDPC methods were then compared regarding conformity index (CI), homogeneity index (HI) of the target, organs at risk (OARs) sparing and monitor units (MUs). The BDPC method provided better HI/CI by 54%/7% on average compared to the CO method and by 38%/3% compared to the STO method. The BDPC method also spared most of the OARs by up to 9%. The average MUs of the CO, STO and BDPC plans were 890, 937 and 1023, respectively. Our results indicated that the BDPC method can effectively improve the dose distribution in IMRT for stage III lung cancer, at the expense of more MUs.

Flattening Filter-Free Beams in Intensity-Modulated Radiotherapy and Volumetric Modulated Arc Therapy for Sinonasal Cancer.

PURPOSE: To evaluate the dosimetric impacts of flattening filter-free (FFF) beams in intensity-modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) for sinonasal cancer. METHODS: For fourteen cases, IMRT and VMAT planning was performed using 6-MV photon beams with both conventional flattened and FFF modes. The four types of plans were compared in terms of target dose homogeneity and conformity, organ-at-risk (OAR) sparing, number of monitor units (MUs) per fraction, treatment time and pure beam-on time. RESULTS: FFF beams led to comparable target dose homogeneity, conformity, increased number of MUs and lower doses to the spinal cord, brainstem and normal tissue, compared with flattened beams in both IMRT and VMAT. FFF beams in IMRT resulted in improvements by up to 5.4% for sparing of the contralateral optic structures, with shortened treatment time by 9.5%. However, FFF beams provided comparable overall OAR sparing and treatment time in VMAT. With FFF mode, VMAT yielded inferior homogeneity and superior conformity compared with IMRT, with comparable overall OAR sparing and significantly shorter treatment time. CONCLUSIONS: Using FFF beams in IMRT and VMAT is feasible for the treatment of sinonasal cancer. Our results suggest that the delivery mode of FFF beams may play an encouraging role with better sparing of contralateral optic OARs and treatment efficiency in IMRT, but yield comparable results in VMAT.

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.

A simple optimization approach for improving target dose homogeneity in intensity-modulated radiotherapy for sinonasal cancer.

Homogeneous target dose distribution in intensity-modulated radiotherapy (IMRT) for sinonasal cancer (SNC) is challenging to achieve. To solve this problem, we established and evaluated a basal-dose-compensation (BDC) optimization approach, in which the treatment plan is further optimized based on the initial plans. Generally acceptable initial IMRT plans for thirteen patients were created and further optimized individually by (1) the BDC approach and (2) a local-dose-control (LDC) approach, in which the initial plan is further optimized by addressing hot and cold spots. We compared the plan qualities, total planning time and monitor units (MUs) among the initial, BDC, LDC IMRT plans and volumetric modulated arc therapy (VMAT) plans. The BDC approach provided significantly superior dose homogeneity/conformity by 23%-48%/6%-9% compared with both the initial and LDC IMRT plans, as well as reduced doses to the organs at risk (OARs) by up to 18%, with acceptable MU numbers. Compared with VMAT, BDC IMRT yielded superior homogeneity, inferior conformity and comparable overall OAR sparing. The planning of BDC, LDC IMRT and VMAT required 30, 59 and 58 minutes on average, respectively. Our results indicated that the BDC optimization approach can achieve significantly better dose distributions with shorter planning time in the IMRT for SNC.

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.

Dosimetric Evaluation of a Simple Planning Technique for Improving Intensity-Modulated Radiotherapy for Nasopharyngeal Cancer.

PURPOSE: To evaluate the dosimetric outcomes of a simple planning technique for improving intensity-modulated radiotherapy (IMRT) for nasopharyngeal cancer (NPC). METHODS: For 39 NPC cases, generally acceptable original plans were generated and were improved by the two planning techniques, respectively: (1) a basal-dose-compensation (BDC) technique, in which the treatment plans were re-optimized based on the original plans; (2) a local-dose-control (LDC) technique, in which the original plans were re-optimized with constraints for hot and cold spots. The BDC, original, and LDC plans were then compared regarding homogeneity index (HI) and conformity index (CI) of planning target volumes (PTVs), organ-at-risk (OAR) sparing and monitor units (MUs) per fraction. The whole planning times were also compared between the BDC and LDC plans. RESULTS: The BDC plans had superior HIs / CIs, by 13-24% / 3-243%, respectively, over the original plans. Compared to the LDC plans, the BDC plans provided better HIs only for PTVnx (the PTV of nasopharyngeal primary tumor) by 11% and better CIs for all PTVs by 2-134%. The BDC technique spared most OARs, by 1-9%. The average MUs of the BDC, original, and LDC plans were 2149, 2068 and 2179, respectively. The average whole planning times were 48 and 69 minutes for the BDC and LDC plans, respectively. CONCLUSIONS: For the IMRT of nasopharyngeal cancer, the BDC planning technique can improve target dose homogeneity, conformity and OAR sparing, with better planning efficiency.

Improving target coverage and organ-at-risk sparing in intensity-modulated radiotherapy for cervical oesophageal cancer using a simple optimisation method.

PURPOSE: To assess the performance of a simple optimisation method for improving target coverage and organ-at-risk (OAR) sparing in intensity-modulated radiotherapy (IMRT) for cervical oesophageal cancer. METHODS: For 20 selected patients, clinically acceptable original IMRT plans (Original plans) were created, and two optimisation methods were adopted to improve the plans: 1) a base dose function (BDF)-based method, in which the treatment plans were re-optimised based on the original plans, and 2) a dose-controlling structure (DCS)-based method, in which the original plans were re-optimised by assigning additional constraints for hot and cold spots. The Original, BDF-based and DCS-based plans were compared with regard to target dose homogeneity, conformity, OAR sparing, planning time and monitor units (MUs). Dosimetric verifications were performed and delivery times were recorded for the BDF-based and DCS-based plans. RESULTS: The BDF-based plans provided significantly superior dose homogeneity and conformity compared with both the DCS-based and Original plans. The BDF-based method further reduced the doses delivered to the OARs by approximately 1-3%. The re-optimisation time was reduced by approximately 28%, but the MUs and delivery time were slightly increased. All verification tests were passed and no significant differences were found. CONCLUSION: The BDF-based method for the optimisation of IMRT for cervical oesophageal cancer can achieve significantly better dose distributions with better planning efficiency at the expense of slightly more MUs.

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.

p54nrb/NONO regulates cyclic AMP-dependent glucocorticoid production by modulating phosphodiesterase mRNA splicing and degradation.

Glucocorticoid production in the adrenal cortex is activated in response to an increase in cyclic AMP (cAMP) signaling. The nuclear protein p54(nrb)/NONO belongs to the Drosophila behavior/human splicing (DBHS) family and has been implicated in several nuclear processes, including transcription, splicing, and RNA export. We previously identified p54(nrb)/NONO as a component of a protein complex that regulates the transcription of CYP17A1, a gene required for glucocorticoid production. Based on the multiple mechanisms by which p54(nrb)/NONO has been shown to control gene expression and the ability of the protein to be recruited to the CYP17A1 promoter, we sought to further define the molecular mechanism by which p54(nrb)/NONO confers optimal cortisol production. We show here that silencing p54(nrb)/NONO expression in H295R human adrenocortical cells decreases the ability of the cells to increase intracellular cAMP production and subsequent cortisol biosynthesis in response to adrenocorticotropin hormone (ACTH) stimulation. Interestingly, the expression of multiple phosphodiesterase (PDE) isoforms, including PDE2A, PDE3A, PDE3B, PDE4A, PDE4D, and PDE11A, was induced in p54(nrb)/NONO knockdown cells. Investigation of the mechanism by which silencing of p54(nrb)/NONO led to increased expression of select PDE isoforms revealed that p54(nrb)/NONO regulates the splicing of a subset of PDE isoforms. Importantly, we also identify a role for p54(nrb)/NONO in regulating the stability of PDE transcripts by facilitating the interaction between the exoribonuclease XRN2 and select PDE transcripts. In summary, we report that p54(nrb)/NONO modulates cAMP-dependent signaling, and ultimately cAMP-stimulated glucocorticoid biosynthesis by regulating the splicing and degradation of PDE transcripts.

More accurate definition of clinical target volume based on the measurement of microscopic extensions of the primary tumor toward the uterus body in international federation of gynecology and obstetrics Ib-IIa squamous cell carcinoma of the cervix.

PURPOSE: To more accurately define clinical target volume for cervical cancer radiation treatment planning by evaluating tumor microscopic extension toward the uterus body (METU) in International Federation of Gynecology and Obstetrics stage Ib-IIa squamous cell carcinoma of the cervix (SCCC). PATIENTS AND METHODS: In this multicenter study, surgical resection specimens from 318 cases of stage Ib-IIa SCCC that underwent radical hysterectomy were included. Patients who had undergone preoperative chemotherapy, radiation, or both were excluded from this study. Microscopic extension of primary tumor toward the uterus body was measured. The association between other pathologic factors and METU was analyzed. RESULTS: Microscopic extension toward the uterus body was not common, with only 12.3% of patients (39 of 318) demonstrating METU. The mean (±SD) distance of METU was 0.32 ± 1.079 mm (range, 0-10 mm). Lymphovascular space invasion was associated with METU distance and occurrence rate. A margin of 5 mm added to gross tumor would adequately cover 99.4% and 99% of the METU in the whole group and in patients with lymphovascular space invasion, respectively. CONCLUSION: According to our analysis of 318 SCCC specimens for METU, using a 5-mm gross tumor volume to clinical target volume margin in the direction of the uterus should be adequate for International Federation of Gynecology and Obstetrics stage Ib-IIa SCCC. Considering the discrepancy between imaging and pathologic methods in determining gross tumor volume extent, we recommend a safer 10-mm margin in the uterine direction as the standard for clinical practice when using MRI for contouring tumor volume.

[Uncertainty analysis of ecological risk assessment caused by heavy-metals deposition from MSWI emission].

The CALPUFF model was applied to simulate the ground-level atmospheric concentrations of Pb and Cd from municipal solid waste incineration (MSWI) plants, and the soil concentration model was used to estimate soil concentration increments after atmospheric deposition based on Monte Carlo simulation, then ecological risk assessment was conducted by the potential ecological risk index method. The results showed that the largest atmospheric concentrations of Pb and Cd were 5.59 x 109-3) microg x m(-3) and 5.57 x 10(-4) microg x m(-3), respectively, while the maxima of soil concentration incremental medium of Pb and Cd were 2.26 mg x kg(-1) and 0.21 mg x kg(-1), respectively; High risk areas were located next to the incinerators, Cd contributed the most to the ecological risk, and Pb was basically free of pollution risk; Higher ecological hazard level was predicted at the most polluted point in urban areas with a 55.30% probability, while in rural areas, the most polluted point was assessed to moderate ecological hazard level with a 72.92% probability. In addition, sensitivity analysis of calculation parameters in the soil concentration model was conducted, which showed the simulated results of urban and rural area were most sensitive to soil mix depth and dry deposition rate, respectively.