Radiation-Induced Lymphopenia and Its Impact on Survival in Patients with Brain Metastasis.

BACKGROUND: Differences in radiation-induced lymphopenia and prognosis between methods of radiotherapy (RT) for brain metastases remain unclear. METHODS: In this retrospective analysis of patients who underwent whole-brain radiotherapy (WBRT) or stereotactic radiosurgery/radiotherapy (SRS/SRT) for brain metastases, baseline total lymphocyte count (TLC) data were obtained within 2 weeks before RT initiation. Follow-up TLC data were evaluated at 0-2, 2-4, and 4-8 weeks after RT completion. Persistent lymphopenia was defined as <800/µL at any time point. RESULTS: Overall, 138 RT courses in 128 patients were eligible (94 WBRT; 44 SRS/SRT). In the WBRT courses, the median baseline TLC was 1325/µL (IQR: 923-1799). Follow-up TLC decreased significantly to 946/µL (626-1316), 992/µL (675-1291), and 1075/µL (762-1435) (p < 0.001). SRS/SRT courses showed no significant TLC decrease. Multivariate analysis revealed female sex, prior RT, baseline TLC < 800/µL, and WBRT use were significantly associated with persistent lymphopenia. In the WBRT group, overall survival was significantly different between those with and without persistent lymphopenia (median, 2.6 and 6.1 months; p < 0.001). However, there was no significant difference in survival in the SRS/SRT group (p = 0.60). CONCLUSION: This study suggests SRS/SRT might be preferable for lymphocyte preservation in brain metastasis patients.

Cone-beam computed tomography-guided online adaptive radiotherapy for pharyngeal cancer with whole neck irradiation: dose-volume histogram analysis between adapted and scheduled plans.

The present study aimed to evaluate whether an adapted plan with Ethos™ could be used for pharyngeal cancer. Ten patients with pharyngeal cancer who underwent chemoradiotherapy with available daily cone-beam computed tomography (CBCT) data were included. Simulated treatments were generated on the Ethos™ treatment emulator using CBCTs every four to five fractions for two plans: adapted and scheduled. The simulated treatments were divided into three groups: early (first-second week), middle (third-fourth week), and late (fifth-seventh week) periods. Dose-volume histogram parameters were compared for each period between the adapted and scheduled plans in terms of the planning target volume (PTV) (D98%, D95%, D50% and D2%), spinal cord (Dmax and D1cc), brainstem (Dmax) and ipsilateral and contralateral parotid glands (Dmedian and Dmean). The PTV D98%, D95% and D2% of the adapted plan were significantly higher than those of the scheduled plans in all periods, except for D98% in the late period. The adapted plan significantly reduced the spinal cord Dmax and D1cc compared with the scheduled plan in all periods. Ipsilateral and contralateral parotid glands Dmean of the adapted plan were lower than those of scheduled plan in the late period. In conclusion, the present study revealed that the adapted plans could maintain PTV coverage while reducing the doses to organs at risk in each period compared with scheduled plans.

Clinical outcomes and failure patterns after postoperative radiotherapy for oral cavity squamous cell carcinoma.

PURPOSE: This study aimed to assess recurrence patterns and identify the optimal dose and target volumes of postoperative radiotherapy (PORT) in patients with oral cavity squamous cell carcinoma (OSCC). METHODS: Data of 111 patients who received PORT for OSCC between January 2010 and April 2020 were retrospectively reviewed. The median age was 68 years (range 19-88). PORT was administered as initial treatment to 63 patients and as salvage treatment for recurrent tumors to 48 patients. The median prescribed dose was 60 Gy (range 50-66) administered in 30 fractions (range 25-33). RESULTS: Median follow-up time was 73 months (range 24-147). Overall survival (OS), progression-free survival (PFS), local control (LC), and locoregional control (LRC) at 3 years were 55.6%, 45.6%, 74.6%, and 63.1%, respectively. There were no significant differences in OS, PFS, LC, and LRC between the initially diagnosed and postoperative recurrent cases. Of 22 patients (20%) who developed regional nodal recurrences, 17 (15%) and 11 (10%) had in-field and out-of-field recurrences, respectively. Of 105 patients who received irradiation to the primary tumor bed, 24 (23%) developed recurrence at the primary site. The PFS and LC rates were significantly worse in patients receiving ≤ 56 Gy to the primary site than those receiving > 56 Gy (p = 0.016 and p = 0.032, respectively). CONCLUSION: PORT was effective for postoperative recurrences as well as for initially diagnosed oral cavity cancer. Doses greater than 56 Gy to the primary site may be required in PORT for OSCC.

Dose difference between anisotropic analytical algorithm (AAA) and Acuros XB (AXB) caused by target's air content for volumetric modulated arc therapy of head and neck cancer.

Background: We clarified the dose difference between the anisotropic analytical algorithm (AAA) and Acuros XB (AXB) with increasing target's air content using a virtual phantom and clinical cases. Materials and methods: Whole neck volumetric modulated arc therapy (VMAT) plan was transferred into a virtual phantom with a cylindrical air structure at the center. The diameter of the air structure was changed from 0 to 6 cm, and the target's air content defined as the air/planning target volume (PTV) in percent (air/PTV) was varied. VMAT plans were recalculated by AAA and AXB with the same monitor unit (MU) and multi-leaf collimator (MLC) motions. The dose at each air/PTV (5%-30%) was compared between each algorithm with D98%, D95%, D50% and D2% for the PTV. In addition, MUs were also compared with the same MLC motions between the D95% prescription with AAA (AAA_D95%), AXB_D95%, and the prescription to 100% minus air/PTV (AXB_D100%-air/PTV) in clinical cases of head and neck (HNC). Results: When air/PTV increased (5-30%), the dose differences between AAA and AXB for D98%, D95%, D50% and D2% were 3.08-15.72%, 2.35-13.92%, 0.63-4.59%, and 0.14-6.44%, respectively. At clinical cases with air/PTV of 5.61% and 28.19%, compared to AAA_D95%, the MUs differences were, respectively, 2.03% and 6.74% for AXB_D95% and 1.80% and 0.50% for AXB_D100%-air/PTV. Conclusion: The dose difference between AAA and AXB increased as the target's air content increased, and AXB_D95% resulted in a dose escalation over AAA_D95% when the target's air content was ≥ 5%. The D100%-air/PTV of PTV using AXB was comparable to the D95% of PTV using AAA.

Clinical course of longer than five years after definitive radiotherapy for nasopharyngeal carcinoma.

BACKGROUND: This study aimed to reveal the long-term outcomes and late toxicities (> 5 years) after definitive intensity-modulated radiation therapy (IMRT) in patients with nasopharyngeal carcinoma (NPC). METHODS: Data from 43 patients (median age, 55 years; range, 17-72 years) with NPC who underwent definitive IMRT between 2001 and 2018 were analyzed. All patients were alive and disease-free 5 years after IMRT. A total dose of 70 (range, 66-70) Gy was delivered in 35 (33-35) fractions with concurrent cisplatin chemotherapy. RESULTS: The median follow-up duration was 119 (range, 61.5-242.1) months. Three patients developed locoregional failure at 79, 92, and 149 months after IMRT, respectively. Of these, 2 patients died of disease progression at 136 and 153 months after IMRT. One patient died of aspiration pneumonia 141 months after IMRT, despite salvage of the recurrent tumor by re-irradiation. In addition, one patient died of aspiration pneumonia 62 months after the IMRT. Thus, the 10-year overall survival, progression-free survival, and locoregional control rates were 98%, 92%, and 94%, respectively. Grade ≥ 2 and ≥ 3 late toxicities were observed in 28 (65%) and 9 (21%) patients, respectively. Nine second primary cancers, including five tongue cancers and two external auditory canal carcinomas, were observed in seven (16%) patients. CONCLUSION: Late recurrences, severe late toxicities, and second primary cancers were observed > 5 years after IMRT. A long-term follow-up of > 5 years is needed in patients with NPC.

Impact of rectal gas on the planning target volume margin for pelvic bone and prostate matching in prostate cancer patients receiving volumetric-modulated arc therapy.

We performed daily cone-beam computed tomography (CBCT) to determine the impact of rectal gas on the movements of prostate and seminal vesicles (SVs). We aimed to determine the relationship between planning target volume (PTV) margins and rectal gas. In 30 treatments of 15 prostate cancer patients, excessive rectal gas was removed and CBCT images were analyzed. Image registration between planning CT and daily CBCT images before and after rectal gas removal was performed for pelvic bone and prostate matching. The couch movement distance between each matching was considered the prostate movement. In addition, we measured SV tip movement between each matching. The anterior-posterior movement of the prostate before rectal gas removal (3.1 ± 2.9 mm) was significantly greater than that after rectal gas removal (1.2 ± 1.2 mm; p < 0.01). The left-right and superior-inferior movements were similar regardless of the presence or absence of rectal gas. The SV movement distances before and after rectal gas removal were 11.0 ± 5.8 mm and 4.6 ± 3.8 mm, respectively (p < 0.01), in pelvic bone matching, and 8.0 ± 4.2 mm and 3.8 ± 3.2 mm, respectively (p < 0.01), in prostate matching. After rectal gas removal, the SV position did not differ significantly between each matching. In 26 of the 30 treatments, SV movement distance in the presence of rectal gas was >6 mm, which is the minimum PTV margin at our institution. In comparison, after rectal gas removal and prostate matching, only 6 treatments demonstrated an SV movement distance of >6 mm. In the presence of rectal gas, the SVs require greater PTV margins than the prostate. Rectal gas removal should be considered if the movement distance on prostate matching is greater than the minimum PTV margin at treating institution.

External beam radiotherapy combination is a risk factor for bladder cancer in patients with prostate cancer treated with brachytherapy.

PURPOSE: To investigate the risk of bladder cancer (BCa) in patients treated with brachytherapy for prostate cancer (PCa). METHODS: We retrospectively analyzed 583 patients with PCa who underwent brachytherapy with or without external beam radiotherapy (EBRT). We analyzed the disease-free survival (DFS) of BCa in patients with PCa who underwent brachytherapy with or without EBRT. We performed multivariate Cox regression analyses of DFS using age, EBRT, and Brinkman index (BI) score (number of cigarettes smoked per day × number of years smoking) ≥ 200 as variables for BCa after brachytherapy. RESULTS: Fourteen patients (2.4%) developed BCa after brachytherapy with or without EBRT. The percentage of high-grade urothelial carcinoma (UC) was 63.6%. A total of 85.7% of patients had non-muscle invasive BCa, and 14.3% of patients had muscle invasive BCa. DFS was longer in brachytherapy monotherapy than in combination therapy (brachytherapy + EBRT). Multivariate Cox regression analysis showed that a BI score ≥ 200 (Hazard Ratio (HR 8.61; 95% Confidence Interval (CI) 1.12-65.98) and EBRT combination (HR 3.29; 95% CI 1.03-10.52) were significantly associated with BCa development in patients with PCa treated with brachytherapy. Furthermore, patients with BI score ≥ 200 and EBRT combination had a significantly higher risk of BCa compared with patients with BI score < 200 (HR Log-rank test P = 0.010). CONCLUSION: Most cases of BCa after brachytherapy with or without EBRT are high grade and invasive. We hypothesized that the EBRT combination might be a risk factor for BCa in patients with PCa who underwent brachytherapy.

Visualization of tumor hypoxia and re-oxygenation after stereotactic body radiation therapy in early peripheral lung cancer: A prospective study.

BACKGROUND AND PURPOSE: In this study, fluoromisonidazole positron emission tomography (F-MISO PET/CT) was used to evaluate tumor hypoxia and re-oxygenation in patients with lung tumors treated with stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: Patients with T1-2 N0 lung cancer were included in this study. The prescribed dose was 48-52 Gy in four fractions. F-MISO PET/CT was performed twice, before SBRT and 1-3 days after the first irradiation. The maximum standardized uptake value (SUVmax) and tumor/muscle ratio (TMR) were evaluated as indicators of hypoxia. The threshold for hypoxia was defined as a TMR of 1.30 or more. RESULTS: Between 2016 and 2021, 15 patients were included. Pre-treatment tumor hypoxia was observed in nine tumors (60 %). TMR in all six tumors without pre-treatment hypoxia rose after single high-dose irradiation. In contrast, TMR in six of nine tumors with pre-treatment hypoxia dropped after irradiation, suggesting re-oxygenation. Although no local recurrence was noted, regional and/or distant relapses were seen in four patients (27 %). Of these, three had tumors with abnormal F-MISO uptake. The remaining patient had a tumor without signs of hypoxia on pre-treatment PET/CT. The 2-year progression free survival of patients with tumors with and without pre-treatment hypoxia were 30 % and 63 %, respectively (p = 0.319). CONCLUSION: Tumor hypoxia reduced after single high-dose irradiation. Tumor with F-MISO uptake seems to be an unfavorable prognostic factor in lung SBRT.

Difference in failure patterns after stereotactic body radiotherapy for lung cancer according to clinical T stage based on 4D computed tomography.

PURPOSE: Stereotactic body radiotherapy (SBRT) is a treatment option for early-stage lung cancer. We aimed to examine the differences in failure patterns after SBRT according to the clinical T stage. METHODS: A total of 120 patients with early-stage lung cancer (T1-3N0M0) who underwent SBRT were analysed. The clinical stage in patients whose tumours were in contact with the chest wall was confirmed using four-dimensional computed tomography (4D-CT). Local failure, regional node metastasis, and distant metastasis were confirmed from clinical charts. RESULTS: Median follow-up time was 27.5 months (range 7-122) after SBRT. Thirteen patients were restaged from clinical T2 with visceral pleural invasion to T3 with chest wall invasion using 4D-CT analysis. Thirty-seven patients developed recurrences. The median progression-free survival (PFS) and overall survival (OS) were 38.1 and 53.8 months, respectively. The 3­year PFS and OS rates were 50.7% and 60.3%, respectively. A significant difference was observed in PFS according to the clinical T stage (p = 0.001). No significant differences were observed in OS according to the clinical T stage (p = 0.213). The proportion of locoregional failures relative to distant metastasis decreased with progression from T1 to T3. The pleural dissemination rate was significantly higher in T3 tumours than in T1 and T2 tumours (p = 0.010). CONCLUSION: Clinical T stage is associated with PFS after SBRT for lung cancer. There were differences in the failure patterns according to T stage. 4D-CT might provide significant information for assessing chest wall invasion associated with unfavourable PFS.

Organs-at-risk dose constraints in head and neck intensity-modulated radiation therapy using a dataset from a multi-institutional clinical trial (JCOG1015A1).

BACKGROUND: JCOG1015A1 is an ancillary research study to determine the organ-specific dose constraints in head and neck carcinoma treated with intensity-modulated radiation therapy (IMRT) using data from JCOG1015. METHODS: Individual patient data and dose-volume histograms of organs at risk (OAR) were collected from 74 patients with nasopharyngeal carcinoma treated with IMRT who enrolled in JCOG1015. The incidence of late toxicities was evaluated using the cumulative incidence method or prevalence proportion. ROC analysis was used to estimate the optimal DVH cut-off value that predicted toxicities. RESULTS: The 5-year cumulative incidences of Grade (G) 1 myelitis, ≥ G1 central nervous system (CNS) necrosis, G2 optic nerve disorder, ≥ G2 dysphagia, ≥ G2 laryngeal edema, ≥ G2 hearing impaired, ≥ G2 middle ear inflammation, and ≥ G1 hypothyroidism were 10%, 5%, 2%, 11%, 5%, 26%, 34%, and 34%, respectively. Significant associations between DVH parameters and incidences of toxicities were observed in the brainstem for myelitis (D1cc ≥ 55.8 Gy), in the brain for CNS necrosis (D1cc ≥ 72.1 Gy), in the eyeball for optic nerve disorder (Dmax ≥ 36.6 Gy), and in the ipsilateral inner ear for hearing impaired (Dmean ≥ 44 Gy). The optic nerve, pharyngeal constrictor muscle (PCM), and thyroid showed tendencies between DVH parameters and toxicity incidence. The prevalence proportion of G2 xerostomia at 2 years was 17 versus 6% (contralateral parotid gland Dmean ≥ 25.8 Gy vs less). CONCLUSIONS: The dose constraint criteria were appropriate for most OAR in this study, although more strict dose constraints might be necessary for the inner ear, PCM, and brainstem.

Escalated Maximum Dose in the Planning Target Volume Improves Local Control in Stereotactic Body Radiation Therapy for T1-2 Lung Cancer.

Stereotactic body radiotherapy (SBRT) is a treatment option for early-stage lung cancer. The purpose of this study was to investigate the optimal dose distribution and prognostic factors for local control (LC) after SBRT for lung cancer. A total of 104 lung tumors from 100 patients who underwent SBRT using various treatment regimens were analyzed. Dose distributions were corrected to the biologically effective dose (BED). Clinical and dosimetric factors were tested for association with LC after SBRT. The median follow-up time was 23.8 months (range, 3.4-109.8 months) after SBRT. The 1- and 3-year LC rates were 95.7% and 87.7%, respectively. In univariate and multivariate analyses, pathologically confirmed squamous cell carcinoma (SQ), T2 tumor stage, and a Dmax < 125 Gy (BED10) were associated with worse LC. The LC rate was significantly lower in SQ than in non-SQ among tumors that received a Dmax < 125 Gy (BED10) (p = 0.016). However, there were no significant differences in LC rate between SQ and non-SQ among tumors receiving a Dmax ≥ 125 Gy (BED10) (p = 0.198). To conclude, SQ, T2 stage, and a Dmax < 125 Gy (BED10) were associated with poorer LC. LC may be improved by a higher Dmax of the planning target volume.

Feasibility study of volumetric modulated arc therapy with Halcyon™ linac for total body irradiation.

BACKGROUND: The use of total body irradiation (TBI) with linac-based volumetric modulated arc therapy (VMAT) has been steadily increasing. Helical tomotherapy has been applied in TBI and total marrow irradiation to reduce the dose to critical organs, especially the lungs. However, the methodology of TBI with Halcyon™ linac remains unclear. This study aimed to evaluate whether VMAT with Halcyon™ linac can be clinically used for TBI. METHODS: VMAT planning with Halcyon™ linac was conducted using a whole-body computed tomography data set. The planning target volume (PTV) included the body cropped 3 mm from the source. A dose of 12 Gy in six fractions was prescribed for 50% of the PTV. The organs at risk (OARs) included the lens, lungs, kidneys, and testes. RESULTS: The PTV D98%, D95%, D50%, and D2% were 8.9 (74.2%), 10.1 (84.2%), 12.6 (105%), and 14.2 Gy (118%), respectively. The homogeneity index was 0.42. For OARs, the Dmean of the lungs, kidneys, lens, and testes were 9.6, 8.5, 8.9, and 4.4 Gy, respectively. The V12Gy of the lungs and kidneys were 4.5% and 0%, respectively. The Dmax of the testes was 5.8 Gy. Contouring took 1-2 h. Dose calculation and optimization was performed for 3-4 h. Quality assurance (QA) took 2-3 h. The treatment duration was 23 min. CONCLUSIONS: A planning study of TBI with Halcyon™ to set up VMAT-TBI, dosimetric evaluation, and pretreatment QA, was established.

Dosimetric Evaluation of Simplified Knowledge-Based Plan with an Extensive Stepping Validation Approach in Volumetric-Modulated Arc Therapy-Stereotactic Body Radiotherapy for Lung Cancer.

PURPOSE: We investigated the performance of the simplified knowledge-based plans (KBPs) in stereotactic body radiotherapy (SBRT) with volumetric-modulated arc therapy (VMAT) for lung cancer. MATERIALS AND METHODS: For 50 cases who underwent SBRT, only three structures were registered into knowledge-based model: total lung, spinal cord, and planning target volume. We performed single auto-optimization on VMAT plans in two steps: 19 cases used for the model training (closed-loop validation) and 16 new cases outside of training set (open-loop validation) for TrueBeam (TB) and Halcyon (Hal) linacs. The dosimetric parameters were compared between clinical plans (CLPs) and KBPs: CLPclosed, KBPclosed-TB and KBPclosed-Hal in closed-loop validation, CLPopen, KBPopen-TB and KBPopen-Hal in open-loop validation. RESULTS: All organs at risk were comparable between CLPs and KBPs except for contralateral lung: V5 of KBPs was approximately 3%-7% higher than that of CLPs. V20 of total lung for KBPs showed comparable to CLPs; CLPclosed vs. KBPclosed-TB and CLPclosed vs. KBPclosed-Hal: 4.36% ± 2.87% vs. 3.54% ± 1.95% and 4.36 ± 2.87% vs. 3.54% ± 1.94% (P = 0.54 and 0.54); CLPopen vs. KBPopen-TB and CLPopen vs. KBPopen-Hal: 4.18% ± 1.57% vs. 3.55% ± 1.27% and 4.18% ± 1.57% vs. 3.67% ± 1.26% (P = 0.19 and 0.27). CI95 of KBPs with both linacs was superior to that of the CLP in closed-loop validation: CLPclosed vs. KBPclosed-TB vs. KBPclosed-Hal: 1.32% ± 0.12% vs. 1.18% ± 0.09% vs. 1.17% ± 0.06% (P < 0.01); and open-loop validation: CLPopen vs. KBPopen-TB vs. KBPopen-Hal: 1.22% ± 0.09% vs. 1.14% ± 0.04% vs. 1.16% ± 0.05% (P ≤ 0.01). CONCLUSIONS: The simplified KBPs with limited number of structures and without planner intervention were clinically acceptable in the dosimetric parameters for lung VMAT-SBRT planning.

Serum lactate dehydrogenase is a predictive biomarker in patients with oropharyngeal cancer undergoing radiotherapy: Retrospective study on predictive factors.

BACKGROUND: The present study aimed to evaluate the prognostic factors in human papillomavirus (HPV)-positive and HPV-negative oropharyngeal cancer (OPC) treated with definitive radiotherapy. METHODS: We retrospectively evaluated 101 patients with OPC who underwent definitive radiotherapy between 2008 and 2018. RESULTS: The median follow-up period of the surviving patients was 68 months (range, 8-164 months). The 5-year overall survival rate was 69.8%. Univariate analyses revealed that poor survival was associated with male sex, smoking ≥30 pack-years, Eastern Cooperative Oncology Group performance status ≥1, tumor-node-metastasis (TNM) stage III-IV (8th edition), HPV-negativity, serum lactate dehydrogenase (LDH) ≥202, C-reactive protein/albumin ratio ≥0.15, and lymphocyte-to-monocyte ratio <2.90. In multivariate analyses, poor survival was independently correlated with smoking ≥30 pack-years (p < 0.01) and LDH ≥202 (p = 0.02). CONCLUSIONS: The present study suggested that high LDH levels predicted poor survival after definitive radiotherapy for patients with both HPV-positive and HPV-negative OPC.

Outcome of chemoradiotherapy using intensity-modulated radiation therapy for cervical esophageal cancer: a single institute experience.

BACKGROUND: The role of intensity-modulated radiation therapy in the treatment of cervical esophageal cancer remains unclear. The outcome of concurrent chemoradiotherapy for cervical esophageal squamous cell carcinoma using intensity-modulated radiation therapy was retrospectively evaluated. METHODS: Between 2004 and 2017, 36 patients with cervical esophageal cancer treated with intensity-modulated radiation therapy were included. Among these patients, one had stage II disease, three stage III, 19 stage IVA, and 13 stage IVB. All patients received radiotherapy at a dose of 60 Gy and concurrent platinum-based doublet chemotherapy. RESULTS: The median follow-up period for surviving patients was 36 months. Three-year locoregional control, progression-free survival, and overall survival rates were 54, 40, and 46%, respectively. Disease progression was noted in 20 out of 36 patients (56%). Grade 3 late toxicities were observed in four patients (three esophageal stenoses and one carotid artery stenosis). There were no grade 4-5 toxicities. Univariate analysis identified the duration of radiotherapy as a prognostic factor for overall survival. CONCLUSIONS: Chemoradiotherapy using intensity-modulated radiation therapy for locally advanced cervical esophageal carcinoma achieved satisfactory locoregional control and survival with acceptable toxicities.

Influence of Cleaned-up Commercial Knowledge-Based Treatment Planning on Volumetric-Modulated Arc Therapy of Prostate Cancer.

PURPOSE: This study aimed to investigate the influence of cleaned-up knowledge-based treatment planning (KBP) models on the plan quality for volumetric-modulated arc therapy (VMAT) of prostate cancer. MATERIALS AND METHODS: Thirty prostate cancer VMAT plans were enrolled and evaluated according to four KBP modeling methods as follows: (1) model not cleaned - trained by fifty other clinical plans (KBPORIG); (2) cases cleaned by removing plans that did not meet all clinical goals of the dosimetric parameters, derived from dose-volume histogram (DVH) (KBPC-DVH); (3) cases cleaned outside the range of ±1 standard deviation through the principal component analysis regression plots (KBPC-REG); and (4) cases cleaned using both methods (2) and (3) (KBPC-ALL). Rectal and bladder structures in the training models numbered 34 and 48 for KBPC-DVH, 37 and 33 for KBPC-REG, and 26 and 33 for KBPC-ALL, respectively. The dosimetric parameters for each model with one-time auto-optimization were compared. RESULTS: All KBP models improved target dose coverage and conformity and provided comparable sparing of organs at risks (rectal and bladder walls). There were no significant differences in plan quality among the KBP models. Nevertheless, only the KBPC-ALL model generated no cases of >1% V78 Gy (prescribed dose) to the rectal wall, whereas the KBPORIG, KBPC-DVH, and KBPC-REG models included two, four, and three cases, respectively, which were difficult to overcome with KBP because the planning target volume (PTV) and rectum regions overlapped. CONCLUSIONS: The cleaned-up KBP model based on DVH and regression plots improved plan quality in the PTV-rectum overlap region.

Dose-volume Histogram Analysis of Knowledge-based Volumetric-modulated Arc Therapy Planning in Postoperative Breast Cancer Irradiation.

BACKGROUND/AIM: We evaluated the dosimetric profiles of manually generated volumetric-modulated arc therapy (VMAT) plans and performance of a commercial knowledge-based planning system (KBP) in treating breast cancer. MATERIALS AND METHODS: We defined the manually generated VMAT plan as the manual plan (MP). Twenty MPs were generated for left-sided breast cancer patients who underwent breast-conserving surgery and used to develop a KBP training set. The other five patients were used for validation. The dosimetric parameters among MPs, tangential irradiation plans (TPs), and KBP-VMAT plans (KBP-Ps) were compared. RESULTS: D95 and homogeneity of the planning target volume (PTV) were significantly higher and greater in MPs and KBP-Ps than in TPs. Lung V20, V40 The Dmean for the left anterior descending artery was lower in MPs and KBP-Ps than in TPs. KBP could save time in generating VMAT plans. CONCLUSION: MPs and KBP-Ps could ensure higher dose uniformity of PTV than TPs. KBP could faster generate comparable MPs for breast cancer.

Correction: Evaluation of lung toxicity risk with computed tomography ventilation image for thoracic cancer patients.

[This corrects the article DOI: 10.1371/journal.pone.0204721.].

Comparing the 7th and 8th editions of the American Joint Committee on Cancer/Union for International Cancer Control TNM staging system for esophageal squamous cell carcinoma treated by definitive radiotherapy.

BACKGROUND: We retrospectively compared the 7th and the 8th editions of The American Joint Committee on Cancer/Union for International Cancer Control (AJCC/UICC) TNM classification in the cohort of survival of the patients with esophageal squamous cell carcinoma (ESCC) treated by definitive radiotherapy. METHODS: We included in this study 403 patients with ESCC who underwent radiotherapy or chemoradiotherapy, at a total radiation dose of ≥ 50 Gy with curative intent from 2000 to 2016 at Kindai University Hospital, and who had no distant metastasis (excluding supraclavicular lymph node). The same patient data set was re-staged according to both the 7th and 8th editions of AJCC/UICC TNM classification. RESULTS: For the 7th edition, 5-year overall survival (OS) for stages I, II, III, and IV were 58%, 52%, 22%, and 12%, respectively, which seemed to be separable into two groups (Stages I-II and III-IV). In the 8th edition, corresponding values for stages I, II, III, and IV were 65%, 44%, 34%, and 16%, respectively, which seemed to be separated into three groups (Stage I, II-III, and IV). CONCLUSIONS: The 8th edition of AJCC/UICC TNM classification is a useful predictor of OS among ESCC patients who were treated with definitive radiotherapy.

Neutrophil-to-Lymphocyte Ratio Predicts Survival After Whole-brain Radiotherapy in Non-small Cell Lung Cancer.

AIM: This study aimed to identify prognostic factors for response to whole-brain radiotherapy (WBRT) in patients with brain metastases (BMs) from non-small cell lung cancer (NSCLC). PATIENTS AND METHODS: This study retrospectively evaluated 100 patients who underwent WBRT for BMs from NSCLC between December 2012 and October 2017. Clinical factors were tested for associations with overall survival after WBRT. RESULTS: The median follow-up time was 134 days (range=14-1,395 days), the median survival time was 143 days, and the 1-year survival rate was 30.4%. Univariate and multivariate analyses revealed that better survival was independently associated with expression of programmed death-ligand 1 (PD-L1), no previous treatment for BMs, no extracranial disease, and a neutrophil-to-lymphocyte ratio (NLR) of <5.0. CONCLUSION: A low NLR and positive PD-L1 expression independently predict better prognosis in patients with BMs from NSCLC after WBRT. These findings suggest that the potential immune response may influence survival among patients with BMs.