Assessment and validation of glottic motion using cone-beam CT and real-time cine MRI.

PURPOSE: This study aimed to assess the margin for the planning target volume (PTV) using the Van Herk formula. We then validated the proposed margin by real-time magnetic resonance imaging (MRI). METHODS: An analysis of cone-beam computed tomography (CBCT) data from early glottic cancer patients was performed to evaluate organ motion. Deformed clinical target volumes (CTV) after rigid registration were acquired using the Velocity program (Varian Medical Systems, Palo Alto, CA, USA). Systematic (Σ) and random errors (σ) were evaluated. The margin for the PTV was defined as 2.5 Σ + 0.7 σ according to the Van Herk formula. To validate this margin, we accrued healthy volunteers. Sagittal real-time cine MRI was conducted using the ViewRay system (ViewRay Inc., Oakwood Village, OH, USA). Within the obtained sagittal images, the vocal cord was delineated. The movement of the vocal cord was summed up and considered as the internal target volume (ITV). We then assessed the degree of overlap between the ITV and the PTV (vocal cord plus margins) by calculating the volume overlap ratio, represented as (ITV∩PTV)/ITV. RESULTS: CBCTs of 17 early glottic patients were analyzed. Σ and σ were 0.55 and 0.57 for left-right (LR), 0.70 and 0.60 for anterior-posterior (AP), and 1.84 and 1.04 for superior-inferior (SI), respectively. The calculated margin was 1.8 mm (LR), 2.2 mm (AP), and 5.3 mm (SI). Four healthy volunteers participated for validation. A margin of 3 mm (AP) and 5 mm (SI) was applied to the vocal cord as the PTV. The average volume overlap ratio between ITV and PTV was 0.92 (range 0.85-0.99) without swallowing and 0.77 (range 0.70-0.88) with swallowing. CONCLUSION: By evaluating organ motion by using CBCT, the margin was 1.8 (LR), 2.2 (AP), and 5.3 mm (SI). The margin acquired using CBCT fitted well in real-time cine MRI. Given that swallowing during radiotherapy can result in a substantial displacement, it is crucial to consider strategies aimed at minimizing swallowing and related motion.

Intrathoracic Progression Is Still the Most Dominant Failure Pattern after First-Line Chemo-immunotherapy in Extensive-Stage Small-Cell Lung Cancer: Implications for Thoracic Radiotherapy.

PURPOSE: This study aimed to compare the failure patterns before and after the introduction of immunotherapy and to determine the role of thoracic radiotherapy (TRT) in extensive-stage small-cell lung cancer (ES-SCLC) treatment. MATERIALS AND METHODS: We retrospectively reviewed 294 patients with ES-SCLC, of which 62.2% underwent chemotherapy alone, 13.3% underwent chemotherapy followed by consolidative TRT (TRT group), and 24.5% underwent chemotherapy with immune checkpoint inhibitor (ICI group). We performed propensity-score matching (PSM) to compare each treatment group. RESULTS: The median follow-up duration was 10.4 months. At the first relapse, in the cohort showing objective response, the proportion of cases showing intrathoracic progression was significantly lower in the TRT group (37.8%) than in the chemotherapy-alone (77.2%, p < 0.001) and the ICI (60.3%, p=0.03) groups. Furthermore, in the subgroup analysis, TRT showed benefits related to intrathoracic progression-free survival (PFS) in comparison with ICI in patients with less than two involved extrathoracic sites (p=0.008) or without liver metastasis (p=0.02) or pleural metastasis (p=0.005) at diagnosis. After PSM, the TRT group showed significantly better intrathoracic PFS than both chemotherapy-alone and ICI groups (p < 0.001 and p=0.04, respectively), but showed no significant benefit in terms of PFS and overall survival in comparison with the ICI group (p=0.17 and p=0.31, respectively). CONCLUSION: In ES-SCLC, intrathoracic progression was the most dominant failure pattern after immunotherapy. In the era of chemoimmunotherapy, consolidative TRT can still be considered a useful treatment strategy for locoregional control.

Novel tongue-positioning device to reduce tongue motions during radiation therapy for head and neck cancer: Geometric and dosimetric evaluation.

This study aimed to assess the performance of a tongue-positioning device in interfractional tongue position reproducibility by cone-beam computed tomography (CBCT). Fifty-two patients treated with radiation therapy (RT) while using a tongue positioning device were included in the study. All patients were treated with 28 or 30 fractions using the volumetric modulated arc therapy technique. CBCT images were acquired at the 1st, 7th, 11th, 15th, 19th, 23th, and 27th fractions. Tongues on planning computed tomography (pCT) and CBCT images were contoured in the treatment planning system. Geometric differences in the tongue between pCT and CBCT were assessed by the Dice similarity coefficient (DSC) and averaged Hausdorff distance (AHD). Two-dimensional in vivo measurements using radiochromic films were performed in 13 patients once a week during sessions. The planned dose distributions were compared with the measured dose distributions using gamma analysis with criteria of 3%/3 mm. In all patients, the mean DSC at the 1st fraction (pCT versus 1st CBCT) was 0.80 while the mean DSC at the 27th fraction (pCT versus 27th CBCT) was 0.77 with statistical significance (p-value = 0.015). There was no statistically significant difference in DSC between the 1st fraction and any other fraction, except for the 27th fraction. There was statistically significant difference in AHD between the 1st fraction and the 19th, 23th, and 27th fractions (p-value < 0.05). In vivo measurements showed an average gamma passing rate of 90.54%. There was no significant difference between measurements at the 1st week and those at other weeks. The tongue geometry during RT was compared between pCT and CBCT. In conclusion, the novel tongue-positioning device was found to minimize interfractional variations in position and shape of the tongue.

Treatment patterns and results of salvage treatment for regional recurrences after stereotactic ablative radiotherapy for primary non-small cell lung cancer.

PURPOSE: Stereotactic ablative radiotherapy (SABR) for early-stage lung cancer has shown promising results; however, regional recurrence (RR) development is not uncommon, and salvage treatment strategies have not been established. We aimed to investigate treatment patterns, prognostic factors, and survival outcomes. MATERIALS AND METHODS: A retrospective analysis of 391 patients who underwent SABR for primary lung cancer from 2012 to 2019 was performed. Among these patients, 90 patients showed recurrence, including local recurrence (n = 9), RR (n = 33), distant metastasis (DM) (n = 57), and RR with simultaneous DM (n = 8). The median follow-up duration was 17.3 months. RESULTS: The median age was 75 years, and most patients underwent primary SABR due to poor lung function (69.7%). Various salvage treatments were performed in cases of RR, including chemotherapy (n = 15), radiotherapy (n = 7), concurrent chemoradiotherapy (n = 2), and best supportive care (n = 9). The median overall survival (OS) and post-recurrence OS (PR-OS) were 22.9 and 11.2 months, respectively. In multivariate analysis, age ≤75 years (HR = 0.36, p = 0.040), isolated recurrence (HR = 0.34, p = 0.037), and radiotherapy without chemotherapy (HR = 0.25, p = 0.024) were significant prognostic factors for PR-OS. CONCLUSIONS: Despite various salvage treatments, PR-OS was less than 1 year after RR in our frail patients group who underwent primary SABR. The toxicities of salvage chemotherapy could be quite severe; thus, careful patient selection is required. Further research is needed to validate our findings.

Radiation Oncology Research in Asia: Current Status and a Peep Into the Future From the Federation of Asian Organizations for Radiation Oncology.

PURPOSE: This survey was conducted to assess the current research practices among the 14 members of the Federation of Asian Organizations for Radiation Oncology (FARO) committee, to inform measures for research capacity building in these nations. MATERIALS AND METHODS: A 19-item electronic survey was sent to two research committee members from the 14 representative national radiation oncology organizations (N = 28) that are a part of FARO. RESULTS: Thirteen of the 14 member organizations (93%) and 20 of 28 members (71.5%) responded to the questionnaire. Only 50% of the members stated that an active research environment existed in their country. Retrospective audits (80%) and observational studies (75%) were the most common type of research conducted in these centers. Lack of time (80%), lack of funding (75%), and limited training in research methodology (40%) were cited as the most common hindrances in conducting research. To promote research initiatives in the collaborative setting, 95% of the members agreed to the creation of site-specific groups, with head and neck (45%) and gynecological cancers (25%) being the most preferred disease sites. Projects focused on advanced external beam radiotherapy implementation (40%), and cost-effectiveness studies (35%) were cited as some of the potential areas for future collaboration. On the basis of the survey results, after result discussion and the FARO officers meeting, an action plan for the research committee has been created. CONCLUSION: The results from the survey and the initial policy structure may allow facilitation of radiation oncology research in the collaborative setting. Centralization of research activities, funding support, and research-directed training are underway to help foster a successful research environment in the FARO region.

Efficacy of Prophylactic Cranial Irradiation According to the Risk of Extracranial Recurrence in Limited-Stage Small Cell Lung Cancer.

PURPOSE: We aimed to evaluate the effectiveness of prophylactic cranial irradiation (PCI) for "early brain metastasis", which occurs before extracranial recurrence (ECR), and "late brain metastasis", which occurs after ECR, in limited-stage small cell lung cancer (LS-SCLC). Materials and Methods: We retrospectively analyzed 271 LS-SCLC patients who underwent definitive chemoradiation. All patients were initially staged with brain magnetic resonance imaging and positron emission tomography. Intracranial recurrence (ICR), ECR, progression-free rate (PFR), and overall survival (OS) were analyzed as clinical endpoints. The competing risk of the first recurrence with ICR (ICRfirst) was evaluated. Significantly associated variables in multivariate analysis of ECR were considered as ECR risk factors. Patients were stratified according to the number of ECR risk factors. RESULTS: The application of PCI was associated with higher PFR (p=0.008) and OS (p=0.045). However, PCI was not associated with any of the clinical endpoints in multivariate analysis. The competing risk of ICRfirst was significantly decreased with the application of PCI (hazard ratio, 0.476; 95% confidence interval, 0.243 to 0.931; p=0.030). Stage III disease, sequential, and stable disease after thoracic radiation were selected as ECR risk factors. For patients without these risk factors, the application of PCI was significantly associated with increased OS (p=0.048) and a decreased risk of ICRfirst (p=0.026). CONCLUSION: PCI may play a role in preventing early brain metastasis rather than late brain metastasis after ECR, suggesting that only patients with a low risk of ECR may currently benefit from PCI.

Adjuvant radiotherapy in node-negative salivary malignancies of the parotid gland: A multi-institutional analysis.

BACKGROUND AND PURPOSE: To determine the role of adjuvant radiotherapy (ART) in parotid gland cancer without nodal metastasis, we evaluated the survival outcomes, prognostic factors, and dose-response relationships in patients with node-negative parotid gland cancer patients. MATERIALS AND METHODS: Patients who underwent curative parotidectomy and were pathologically diagnosed with parotid gland cancer without regional or distant metastases between 2004 and 2019 were reviewed. The benefit of ART in terms of locoregional control (LRC) and progression-free survival (PFS) were evaluated. RESULTS: In total, 261 patients were included in the analysis. Of them, 45.2 % received ART. The median follow-up period was 66.8 months. Multivariate analysis revealed that histological grade and ART were independent prognostic factors for LRC and PFS (all p <.05). For patients with high-grade histology, ART was associated with a significant improvement in 5-year LRC (p =.005) and PFS (p =.009). Among patients with high-grade histology who completed RT, higher biologic effective dose (≥77 Gy10) significantly increased PFS (adjusted hazard ratio [HR], 0.10 per 1-Gy increase; 95 % confidence interval [CI], 0.02-0.58; p =.010). ART significantly improved LRC (p =.039) in patients with low-to-intermediate histological grade as well per multivariate analysis, and subgroup analyses revealed patients with T3-4 stage and close/positive resection margins (<1 mm) would benefit from ART. CONCLUSION: ART should be strongly recommended for patients with node-negative parotid gland cancer with high-grade histology in terms of disease control and survival. In patients with low-to-intermediate-grade disease, those with high T stage and incomplete resection margin benefit with ART.

Whole-Genome Sequencing Reveals Mutational Signatures Related to Radiation-Induced Sarcomas and DNA-Damage-Repair Pathways.

Radiation-induced sarcoma (RIS) is a rare but serious late complication arising from radiotherapy. Despite unfavorable clinical outcomes, the genomic footprints of ionizing radiation in RIS development remain largely unknown. Hence, this study aimed to characterize RIS genomes and the genomic alterations in them. We analyzed whole-genome sequencing in 11 RIS genomes matched with normal genomes to identify somatic alterations potentially associated with RIS development. Furthermore, the abundance of mutations, mutation signatures, and structural variants in RIS were compared with those in radiation-naïve spontaneous sarcomas. The mutation abundance in RIS genomes, including one hypermutated genome, was variable. Cancer-related genes might show different types of genomic alterations. For instance, NF1, NF2, NOTCH1, NOTCH2, PIK3CA, RB1, and TP53 showed singleton somatic mutations; MYC, CDKN2A, RB1, and NF1 showed recurrent copy number alterations; and NF2, ARID1B, and RAD51B showed recurrent structural variations. The genomic footprints of nonhomologous end joining are prevalent at indels of RIS genomes compared with those in spontaneous sarcoma genomes, representing the genomic hallmark of RIS genomes. In addition, frequent chromothripsis was identified along with predisposing germline variants in the DNA-damage-repair pathways in RIS genomes. The characterization of RIS genomes on a whole-genome sequencing scale highlighted that the nonhomologous end joining pathway was associated with tumorigenesis, and it might pave the way for the development of advanced diagnostic and therapeutic strategies for RIS.

Identification of Genes Involved in EGF-induced Apoptosis Using CRISPR/Cas9 Knockout Screening: Implications for Novel Therapeutic Targets in EGFR-Overexpressing Cancers.

PURPOSE: Exogenous epidermal growth factor (EGF) causes apoptosis in EGF receptor (EGFR)-overexpressing cell lines. The apoptosis-inducing factors could be a therapeutic target. We aimed to determine the mechanism of EGF-induced apoptosis using a genome-wide clustered regularly interspaced short palindromic repeats (CRISPR)-based knockout screen. Materials and Methods: Two-vector system of the human genome-scale CRISPR knockout library v2 was used to target 19,050 genes using 123,411 single guide RNAs (sgRNAs). Recombinant human EGF (100 nM) or distilled water four times was administered to the experimental and control groups, respectively. The read counts of each sgRNA obtained from next-generation sequencing were analyzed using the edgeR algorithm. We used another EGFR-overexpressing cell line (A549) and short hairpin RNAs (shRNAs) targeting five EGF-resistance genes for validation. DUSP1 expression in A431, A549, and HEK293FT cells was calculated using reverse transcription-quantitative polymerase chain reaction. RESULTS: We found 77 enriched and 189 depleted genes in the experimental group using the CRISPR-based knockout screen and identified the top five EGF-resistance genes: DDX20, LHFP, REPS1, DUSP1,<.i> and KRTAP10-12. Transfecting shRNAs targeting these genes into A549 cells significantly increased the surviving fractions after EGF treatment, compared with those observed in the control shRNA-transfected cells. The expression ratio of DUSP1 (inhibits ERK signaling) increased in A431 and A549 cells after EGF treatment. However, DUSP1 expression remained unchanged in HEK293FT cells after EGF treatment. CONCLUSION: The CRISPR-based knockout screen revealed 266 genes possibly responsible for EGF-induced apoptosis. DUSP1 might be a critical component of EGF-induced apoptosis and a novel target for EGFR-overexpressing cancers.

Predictors of Post-chemoradiotherapy Pulmonary Complication in Locally Advanced Non-Small Cell Lung Cancer.

PURPOSE: We investigated the clinical effects and predictive factors of severe post-chemoradiotherapy pulmonary complications (PCPC) in locally advanced non-small cell lung cancer (LA-NSCLC). Materials and Methods: Medical records of 317 patients who underwent definitive concurrent chemoradiation (CCRT) for LA-NSCLC were reviewed retrospectively. PCPC was defined as an event of admission or emergency department visit for acute or subacute pulmonary inflammatory complications, including pneumonitis and pneumonia, within 6 months after CCRT initiation. Patient characteristics, baseline lung function tests, radiation dosimetric parameters, and laboratory tests were analyzed to investigate their association with PCPC. Prognostic endpoints were disease progression rate (DPR) and overall survival (OS). RESULTS: PCPC was reported in 53 patients (16.7%). The OS of patients with PCPC was significantly worse (35.0% in 2 years) than that of patients without PCPC (67.0% in 2 years, p < 0.001). However, 2-year DPRs were 77.0% and 70.7% in patients with and without PCPC, respectively, which were not significantly different (p=0.087). In multivariate logistic regression, PCPC was independently associated with grade ≥ 1 hypoalbuminemia during CCRT (odds ratio [OR], 5.670; 95% confidence interval [CI], 2.487 to 13.40; p < 0.001), lower diffusing capacity of carbon monoxide (DLCO) (per mL/min/mmHg; OR, 0.855; 95% CI, 0.743 to 0.974; p=0.022), and higher lung V5 (per 10%; OR, 1.872; 95% CI, 1.336 to 2.699; p < 0.001). CONCLUSION: PCPC might be a clinical endpoint to evaluate complications and predict the survival of patients subjected to CCRT for LA-NSCLC. Hypoalbuminaemia, DLCO, and lung V5 might predict PCPC in LA-NSCLC.

Effect of postoperative radiotherapy for patients with differentiated thyroid cancer.

OBJECTIVE: We evaluated the efficacy and safety of postoperative radiotherapy (PORT) for differentiated thyroid cancer (DTC) with high risk features. MATERIALS AND METHODS: This retrospective study analyzed 187 patients treated for DTC from 1985 to 2019. DTC referred to nonanaplastic thyroid cancer originating from follicular cells. PORT was defined as the administration of external beam radiation to the thyroid and regional lymph nodes following surgery for initially diagnosed DTC. The patients were included in the analysis if they received PORT or exhibited any of the following features: (a) pT4 or pN1b according to the 8th American Joint Committee on Cancer, (b) poorly differentiated thyroid cancer (PDTC), or (c) unfavourable variants such as anaplastic foci and etc. After 1:1 propensity matching, a total of 108 patients were analyzed according to PORT receipt. The median follow-up duration of the matched group was 10.4 years. RESULTS: After matching, most of the variables became balanced, but the PORT group still had more PDTC and DTC with anaplastic foci. Radioactive iodine (RAI) was less frequently administered in the PORT group. PORT yielded a significantly higher 5-year locoregional recurrence free survival (LRFS) than the No PORT group (5-year LRFS 86.1% vs. 72.7%, p = 0.022), but the 10-year cancer specific survival (CSS) was similar between them (97.8% vs. 85.9%, p = 0.122). The multivariable analysis indicated that PORT was a favourable prognostic factor (Hazard ratio 0.3, 95% Confidence interval 0.1-0.8, p = 0.02) for LRFS, but not for CSS. Among 133 patients without PORT for initial disease, 39 of them received salvage surgery followed by salvage PORT. No severe toxicity after PORT was reported. CONCLUSION: PORT reduced locoregional recurrence in DTC patients without severe toxicity. PORT can be an effective and safe treatment to improve locoregional control in DTC with high risk features. However, further study is warranted to identify those who can benefit from PORT.

Analysis of Once-Daily Thoracic Radiotherapy Dose According to the Underlying Lung Disease in Patients with Limited-Stage Small Cell Lung Cancer Undergoing Concurrent Chemoradiotherapy.

PURPOSE: In the treatment of concurrent chemoradiotherapy (CCRT) in limited-stage small cell lung cancer, the optimal once-daily radiotherapy (RT) dose/fractionation remain unclear although it is the most frequently used. Therefore, this study aimed to compare the treatment outcomes and toxicities of modest dose RT (≤ 54 Gy) with those of standard dose RT (> 54 Gy) and investigate the benefit of the high dose based on patient factors. MATERIALS AND METHODS: Since 2004, our institution has gradually increased the thoracic RT dose. Among the 225 patients who underwent CCRT, 84 patients (37.3%) received > 54 Gy. Because the patients treated with RT > 54 Gy were not randomly assigned, propensity score matching (PSM) was performed. RESULTS: The proportion of patients treated with > 54 Gy increased over time (p=0.014). Multivariate analysis revealed that the overall tumor stage and dose > 54 Gy (hazard ratio, 0.65; p=0.029) were independent prognostic factors for overall survival (OS). PSM confirmed that thoracic RT doses of > 54 Gy showed significantly improved progression-free survival (3-year, 42.7% vs. 24.0%; p < 0.001) and OS (3-year, 56.2% vs. 38.5%; p=0.003). Sensitivity analysis also showed that 60 Gy resulted in better survival than 54 Gy. However, in patients with underlying lung disease, OS benefit from > 54 Gy was not observed but considerable rates of severe pulmonary toxicities were observed (p=0.001). CONCLUSION: Our analysis supports that the 60 Gy RT dose should be considered in the once-daily regimen of CCRT for limited-stage small cell lung cancer without underlying lung disease, but RT dose > 54 Gy did not seem to benefit for patients with chronic obstructive pulmonary disease or interstitial lung disease. Further study is needed to validate these results.

Prediction and clinical impact of delayed lymphopenia after chemoradiotherapy in locally advanced non-small cell lung cancer.

Introduction: The dosimetric factors of radiotherapy have an acute impact on the host immune system during chemoradiotherapy (CRT) in locally advanced non-small cell lung cancer (NSCLC). However, even after CRT, a substantial number of patients remain immunosuppressed with delayed lymphopenia. Therefore, we aimed to evaluate clinical and dose-volumetric predictors of delayed lymphopenia after CRT in locally advanced NSCLC. Materials and methods: We retrospectively reviewed 272 patients with locally advanced NSCLC who received definitive CRT from January 2012 to August 2020. Differential blood count data, including serum albumin values, were obtained at baseline, during and at first follow up after CRT. Acute and delayed lymphopenia events were defined as grade III/IV lymphopenia developed during or 4-12 weeks after CRT completion, which accounted for 84% and 10% of cases, respectively. Dose-volume histogram parameters for planned target volume, whole body, heart, lung, great vessels, spleen, esophagus and thoracic vertebral bodies were evaluated. Results: Multivariate analysis revealed that patients with delayed lymphopenia were associated with inferior overall survival (HR 2.53, P = 0.001) and progression-free survival (HR 1.98, P = 0.006). However, there was no significant survival difference between groups stratified by acute lymphopenia. On multivariable logistic regression models, lung V5, baseline ALC, during-CRT ALC, and albumin nadir were significant predictors for delayed lymphopenia. Furthermore, the nomogram for delayed lymphopenia based on these variables had good discrimination (area under the curve, 0.905). Conclusions: In this study, we investigated the prognostic significance of delayed lymphopenia and identified clinico-dosimetric parameters to predict delayed lymphopenia.

Evaluation of Optimal Assessment Schedules for Surveillance After Definitive Locoregional Treatment of Locally Advanced Head and Neck Cancer: A Retrospective Cohort Study With Parametric Modeling of Event-Free Survival.

Importance: In clinical practice, assessment schedules are often arbitrarily determined after definitive treatment of head and neck cancer (HNC), producing heterogeneous and inconsistent surveillance plans. Objective: To establish an optimal assessment schedule for patients with definitively treated locally advanced HNC, stratified by the primary subsite and HPV status, using a parametric model of standardized event-free survival curves. Design, Setting, and Participants: This was a retrospective study including 2 tertiary referral hospitals and a total of 673 patients with definitive locoregional treatment of locally advanced HNC (227 patients with nasopharyngeal cancer [NPC]; 237 patients with human papillomavirus-positive oropharyngeal cancer [HPV+ OPC]; 47 patients with HPV-negative [HPV-] OPC; 65 patients with hypopharyngeal cancer [HPC]; and 97 patients with laryngeal cancer [LC]). Patients had received primary treatment in 2008 through 2019. The median (range) follow-up duration was 57.8 (6.4-158.1) months. Data analyses were performed from April to October 2021. Main Outcomes and Measures: Tumor recurrence and secondary malignant neoplasms. Event-free survival was defined as the period from the end of treatment to occurrence of any event. Event-free survival curves were estimated using a piecewise exponential model and divided into 3 phases of regular follow-up. A 5% event rate criterion determined optimal follow-up time point and interval. Results: The median (range) age of the 673 patients at HNC diagnosis was 58 (15-83) years; 555 (82.5%) were men; race and ethnicity were not considered. The event rates of NPC, HPV+ OPC, HPV- OPC, HPC, and LC were 18.9% (43 of 227), 14.8% (35 of 237), 36.2% (17 of 47), 44.6% (29 of 65), and 30.9% (30 of 97), respectively. Parametric modeling demonstrated optimal follow-up intervals for HPC, LC, and NPC, respectively, every 2.1, 3.2, and 6.1 months; 3.7, 5.6, and 10.8 months; and 9.1, 13.8, and 26.5 months until 16.5, 16.5 to 25.0, and 25.0 to 99.0 months posttreatment (open follow-up thereafter). For HPV- OPC, assessment was recommended every 2.7, 4.8, and 11.8 months until 16.5, 16.5 to 25.0, and 25 to 99 months posttreatment, respectively. In contrast, HPV+ OPC optimal intervals were every 7.7, 13.7, and 33.7 months until 16.5, 16.5 to 25.0, and 25 to 99 months posttreatment, respectively. Five, 4, 12, 15, and 10 follow-up visits were recommended for NPC, HPV+ OPC, HPV- OPC, HPC, and LC, respectively. Conclusions and Relevance: This retrospective cohort study using parametric modeling suggests that the HNC assessment schedules should be patient tailored and evidence based to consider primary subsites and HPV status. Given limited health care resources and rising detection rates and costs of HNC, the guidelines offered by these findings could benefit patients and health systems and aid in developing future consensus guidelines.

Hypofractionated radiotherapy for early stage glottic cancer: efficacy of 3.5 Gy per fraction.

PURPOSE: The purpose of this study was to evaluate the treatment outcomes and toxicity profile of patients with early glottic cancer who underwent hypofractionated radiation therapy (RT) with 3.5 Gy per fraction. MATERIALS AND METHODS: A retrospective review was performed of the medical records of 35 patients with early stage (T1-2N0M0) glottic cancer who underwent definitive RT. The dose fractionation scheme was 59.5 Gy in 17 fractions. Posterior commissure was excluded from the clinical target volume (CTV) for 26 patients (74.3%) without glottic lesions close to this region. RESULTS: With a median follow-up of 16.23 months (range, 6.82 to 67.15 months), no local, regional, or distant recurrence was reported. Acute hoarseness (65.7%), mucositis (68.6%), radiation dermatitis (60.0%) was frequent. One patient (2.9%) reported grade 3 acute toxicity (mucositis) and there was no grade 4-5 acute toxicity. There was no grade ≥3 late toxicities; however, grade 1 late intermittent hoarseness was frequent (45.7%). The receiver operative characteristic analysis revealed that mean hypopharyngeal dose was predictive for acute grade ≥2 mucositis (area under the curve=0.9314; 95% confidence interval, 0.8524-1). The optimal threshold of mean hypopharyngeal dose for occurrence of acute grade ≥2 mucositis was 26.31 Gy, with a specificity and sensitivity of 83.3% and 88.2%, respectively. CONCLUSION: Hypofractionated RT with fraction size of 3.5 Gy for early glottic cancer is effective. The hypopharyngeal mean dose could predict the occurrence of grade ≥2 acute mucositis. The posterior commissure can be safely excluded from the CTV.

Aggressive Treatment Including Endonasal Surgical Sequestrectomy with Vascularized Nasoseptal Flap Can Improve Outcomes of Skull Base Osteoradionecrosis.

Objective Skull base osteoradionecrosis (SB-ORN) is a serious, potentially lethal complication of radiation therapy. We aimed to review the clinical characteristics and outcomes of SB-ORN according to the extent of treatment. Design Retrospective analysis design was used for this study. Setting The study was conducted in two tertiary care hospitals. Participants Patients included who had been clinically diagnosed with SB-ORN from January 2006 to 2017. Main Outcome Measures Clinical characteristics, including demographics, predisposing factors, presenting symptoms, radiological findings, treatment modalities, and treatment outcomes, were reviewed. Treatment was classified into conservative and aggressive types. Aggressive treatment included radical surgical removal of soft tissue and bony sequestrum with the placement of vascularized tissue. Treatment outcome was analyzed in terms of clinical control, survival, and carotid artery blow out. Results Fifteen patients (11 males and 4 females) were identified during the study period. Eight patients were managed conservatively, whereas seven patients were managed with aggressive treatment. The 2-year survival was 75% in the aggressive treatment group and 15% in the conservative group (log-rank, p = 0.049). The estimated 2-year blow out free rate was 46.7% for the conservative group and 100% for the aggressive group (log-rank, p = 0.100). Conclusion In patients with SB-ORN, aggressive management, including surgical removal of sequestrum and coverage with a pedicled flap, is associated with increased survival.

Performance evaluation of a visual guidance patient-controlled respiratory gating system for respiratory-gated magnetic-resonance image-guided radiation therapy.

The performance of a visual guidance patient-controlled (VG-PC) respiratory gating system for magnetic-resonance (MR) image-guided radiation therapy (MR-IGRT) was evaluated through a clinical trial of patients with either lung or liver cancer. Patients can voluntarily control their respiration utilizing the VG-PC respiratory gating system. The system enables patients to view near-real-time cine planar MR images projected inside the bore of MR-IGRT systems or an external screen. Twenty patients who had received stereotactic ablative radiotherapy (SABR) for lung or liver cancer were prospectively selected for this study. Before the first treatment, comprehensive instruction on the VG-PC respiratory gating system was provided to the patients. Respiratory-gated MR-IGRT was performed for each patient with it in the first fraction and then without it in the second fraction. For both the fractions, the total treatment time, beam-off time owing to the respiratory gating, and number of beam-off events were analyzed. The average total treatment time, beam-off time, and number of beam-off events with the system were 1507.3 s, 679.5 s, and 185, respectively, and those without the system were 2023.7 s (p < 0.001), 1195.0 s (p < 0.001), and 380 times (p < 0.001), respectively. The VG-PC respiratory gating system improved treatment efficiency through a reduction in the beam-off time, the number of beam-off events, and consequently the total treatment time when performing respiratory-gated MR-IGRT for lung and liver SABR.

Development of an anthropomorphic multimodality pelvic phantom for quantitative evaluation of a deep-learning-based synthetic computed tomography generation technique.

PURPOSE: The objective of this study was to fabricate an anthropomorphic multimodality pelvic phantom to evaluate a deep-learning-based synthetic computed tomography (CT) algorithm for magnetic resonance (MR)-only radiotherapy. METHODS: Polyurethane-based and silicone-based materials with various silicone oil concentrations were scanned using 0.35 T MR and CT scanner to determine the tissue surrogate. Five tissue surrogates were determined by comparing the organ intensity with patient CT and MR images. Patient-specific organ modeling for three-dimensional printing was performed by manually delineating the structures of interest. The phantom was finally fabricated by casting materials for each structure. For the quantitative evaluation, the mean and standard deviations were measured within the regions of interest on the MR, simulation CT (CTsim ), and synthetic CT (CTsyn ) images. Intensity-modulated radiation therapy plans were generated to assess the impact of different electron density assignments on plan quality using CTsim and CTsyn . The dose calculation accuracy was investigated in terms of gamma analysis and dose-volume histogram parameters. RESULTS: For the prostate site, the mean MR intensities for the patient and phantom were 78.1 ± 13.8 and 86.5 ± 19.3, respectively. The mean intensity of the synthetic image was 30.9 Hounsfield unit (HU), which was comparable to that of the real CT phantom image. The original and synthetic CT intensities of the fat tissue in the phantom were -105.8 ± 4.9 HU and -107.8 ± 7.8 HU, respectively. For the target volume, the difference in D95% was 0.32 Gy using CTsyn with respect to CTsim values. The V65Gy values for the bladder in the plans using CTsim and CTsyn were 0.31% and 0.15%, respectively. CONCLUSION: This work demonstrated that the anthropomorphic phantom was physiologically and geometrically similar to the patient organs and was employed to quantitatively evaluate the deep-learning-based synthetic CT algorithm.

Reducing target volume in definitive radiotherapy for human papillomavirus-associated tonsil cancer.

BACKGROUND: To evaluate the efficacy and safety of reducing target volume in definitive radiotherapy for HPV-associated tonsil cancer. METHODS: A single-institution cohort of 90 patients with human papillomavirus (HPV)-associated tonsil cancer who received definitive radiotherapy with a 5-mm expansion from the gross tumor volume to clinical target volume between 2008 and 2019 were included. The overlapping volume of initial planning target volume and the recurrent tumor was calculated and categorized as one of three failure types: in-field: ≥95%; marginal-field: 50%-94%; and out-field: <50%. RESULTS: With a median follow-up of 59.4 months, the 3-year and 5-year local control rates were 94.4% and 92.8%, respectively. A total of seven local failures were identified, of which 4 (4.4%) were in-field, 2 (2.2%) were marginal-field, and 1 (1.1%) was out-field. Grade 3 acute and late toxicities developed in 30 (33.3%) and 5 (5.6%) patients, respectively. CONCLUSIONS: Reducing target volume could be an alternative option for selected patients with HPV-associated tonsil cancer.

Feasibility and safety of neck level IB-sparing radiotherapy in nasopharyngeal cancer: a long-term single institution analysis.

PURPOSE: Nasopharyngeal cancer (NPC) has a higher prevalence of regional nodal metastasis than other head and neck cancers; however, level IB lymph node involvement is rare. We evaluated the safety and feasibility of level IB-sparing radiotherapy (RT) for NPC patients. MATERIALS AND METHODS: We retrospectively reviewed 236 patients with NPC who underwent definitive intensity-modulated RT with or without chemotherapy between 2004 and 2018. Of them, 212 received IB-sparing RT, and 24 received non-IB-sparing RT. We conducted a propensity score matching analysis to compare treatment outcomes according to IB-sparing status. In addition, dosimetric analysis of the salivary glands was performed to identify the relationship between xerostomia and the IB-sparing RT. RESULTS: The median follow-up duration was 78 months (range, 7 to 194 months). Local, regional, and distant recurrences were observed in 11.9%, 6.8%, and 16.1% of patients, respectively. Of the 16 patients with regional recurrence, 14 underwent IB-sparing RT. The most common site categorization of regional recurrence was level II (75%), followed by retropharyngeal lymph nodes (43.8%); however, there was no recurrence at level IB. In the matched cohorts, IB-sparing RT was not significantly related to treatment outcomes. However, IB-sparing RT patients received a significantly lower mean ipsilateral and contralateral submandibular glands doses (all, p < 0.001) and had a lower incidence of chronic xerostomia compared with non-IB-sparing RT patients (p = 0.006). CONCLUSION: Our results demonstrated that IB-sparing RT is sufficiently safe and feasible for treating NPC. To reduce the occurrence of xerostomia, IB-sparing RT should be considered without compromising target coverage.