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Purpose: Stereotactic body radiation therapy (SBRT) is a standard treatment for early primary lung cancer patients. However, there are few simple models for predicting the clinical outcomes of these patients. Our study analyzed the clinical outcomes, identified the prognostic factors, and developed prediction nomogram models for these patients. Materials and Methods: We retrospectively analyzed 114 patients with primary lung cancer treated with SBRT from 2012 to 2020 at our institutions and assessed patient's clinical outcomes and levels of toxicity. Kaplan–Meier analysis with a log-rank test was used to generate the survival curve. The cut-off values of continuous factors were calculated with the X-tile tool. Potential independent prognostic factors for clinical outcomes were explored using cox regression analysis. Nomograms for clinical outcomes prediction were established with identified factors and assessed by calibration curves. Results: The median overall survival (OS) was 40.6 months, with 3-year OS, local recurrence free survival (LRFS), distant disease-free survival (DDFS) and progression free survival (PFS) of 56.3%, 61.3%, 72.9% and 35.8%, respectively, with grade 3 or higher toxicity rate of 7%. The cox regression analysis revealed that the clinical stage, immobilization device, and the prescription dose covering 95% of the target area (D95) were independent prognostic factors associated with OS. Moreover, the clinical stage, and immobilization device were independent prognostic factors of LRFS and PFS. The smoking status, hemoglobin (Hb) and immobilization device were significant prognostic factors for DDFS. The nomograms and calibration curves incorporating the above factors indicated good predictive accuracy. Conclusions: SBRT is effective and safe for primary lung cancer. The prognostic factors associated with OS, LRFS, DDFS and PFS are proposed, and the nomograms we proposed are suitable for clinical outcomes prediction. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Hemoglobin dissociation is of great interest in protein process and clinical medicine as well as in artificial blood research. However, the pathway and mechanisms of pH-dependent human Hb dissociation are not clear, whether Hb would really dissociate into monomers is still a question. Therefore, we have conducted a multi-technique investigation on the structure and function of human Hb versus pH. Here we demonstrate that tetramer hemoglobin can easily dissociate into dimer in abnormal pH and the tetramer → dimer dissociation is reversible if pH returns to normal physiological value. When the environmental pH becomes more acidic (<6.5) or alkaline (>8.0), Hb can further dissociate from dimer to monomer. The proportion of monomers increases while the fraction of dimers decreases as pH declines from 6.2 to 5.4. The dimer → monomer dissociation is accompanied with series changes of protein structure thus it is an irreversible process. The structural changes in the dissociated Hbs result in some loss of their functions. Both the Hb dimer and monomer cannot adequately carry and release oxygen to the tissues in circulation. These findings provide a comprehensive understanding on the pH-dependent protein transitions of human Hb, give guideline to explain complex protein processes and the means to control protein dissociation or re-association reaction. They are also of practical value in clinical medicine, blood preservation and blood substitute development. [ABSTRACT FROM AUTHOR]

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 (d T ), 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 d T 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 d T 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 d T 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., Competing Interests: Competing Interests: The authors have declared that no competing interest exists.

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., Competing Interests: Disclosure The authors report no conflicts of interest in this work.

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 (ESO whole ); ESO whole within the treatment field (ESO infield ); ESO infield , excluding the tumor (ESO infield-tumor ) and ESO whole , excluding the tumor (ESO whole-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 ESO whole , ESO infield , ESO infield-tumor and ESO whole-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.

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., Competing Interests: No conflicts of interest from all participating authors.

We demonstrate that reactive oxygen species (ROS) plays an important role in the process of apoptosis in human peripheral blood mononuclear cell (PBMC) which is induced by the radiation of 900 MHz radiofrequency electromagnetic field (RFEMF) at a specific absorption rate (SAR) of ~0.4 W/kg when the exposure lasts longer than two hours. The apoptosis is induced through the mitochondrial pathway and mediated by activating ROS and caspase-3, and decreasing the mitochondrial potential. The activation of ROS is triggered by the conformation disturbance of lipids, protein, and DNA induced by the exposure of GSM RFEMF. Although human PBMC was found to have a self-protection mechanism of releasing carotenoid in response to oxidative stress to lessen the further increase of ROS, the imbalance between the antioxidant defenses and ROS formation still results in an increase of cell death with the exposure time and can cause about 37% human PBMC death in eight hours.