Intensity-modulated Radiotherapy Research Articles

Case report: A rare case of a long-term survivor of glioblastoma who underwent two courses of hypofractionated radiotherapy as part of her care

Glioblastoma (GB) is a primary brain tumor that is lethal and challenging to treat. The 3-year overall survival (OS) of patients with this diagnosis has stayed the same since 2005. The patient is a 75-year-old woman who presented with progressive aphasia and was diagnosed with GB (WHO grade 4, IDH1/IDH2 wild type, ATRX intact, p53 and PTEN mutant, BRAF non-mutated, O6-methylguanine-DNA methyltransferase promoter methylated) and who underwent surgical resection, hypofractionated radiotherapy (HFRT) using intensity-modulated radiotherapy (IMRT) (4,005 cGy in 15 fractions) alone, and adjuvant temozolomide (TMZ). She was progression-free for approximately 20 months. Although planned, concurrent TMZ was not used during the complete first course of HFRT due to the patient’s performance status. After recurrence, another HFRT (35 Gy in 10 fractions) was employed. She was progression-free on imaging for 8 months until a recent follow-up scan showed potential progression versus radiation-related change. At the time of this case report, her care is still ongoing. This represents a rare case of a long-term survivor of GB who has received two courses of HFRT, a treatment option that is usually used in those with predicted shorter survival times.

Interval Analysis-Based Optimization: A Robust Model for Intensity-Modulated Radiotherapy (IMRT)

Background: Cancer remains one of the leading causes of mortality worldwide, with radiotherapy playing a crucial role in its treatment. Intensity-modulated radiotherapy (IMRT) enables precise dose delivery to tumors while sparing healthy tissues. However, geometric uncertainties such as patient positioning errors and anatomical deformations can compromise treatment accuracy. Traditional methods use safety margins, which may lead to excessive irradiation of healthy organs or insufficient tumor coverage. Robust optimization techniques, such as minimax approaches, attempt to address these uncertainties but can result in overly conservative treatment plans. This study introduces an interval analysis-based optimization model for IMRT, offering a more flexible approach to uncertainty management. Methods: The proposed model represents geometric uncertainties using interval dose influence matrices and incorporates Bertoluzza’s metric to balance tumor coverage and organ-at-risk (OAR) protection. The θ parameter allows controlled robustness modulation. The model was implemented in matRad, an open-source treatment planning system, and evaluated on five prostate cancer cases. Results were compared against traditional Planning Target Volume (PTV) and minimax robust optimization approaches. Results: The interval-based model improved tumor coverage by 5.8% while reducing bladder dose by 4.2% compared to PTV. In contrast, minimax robust optimization improved tumor coverage by 25.8% but increased bladder dose by 23.2%. The interval-based approach provided a better balance between tumor coverage and OAR protection, demonstrating its potential to enhance treatment effectiveness without excessive conservatism. Conclusions: This study presents a novel framework for IMRT planning that improves uncertainty management through interval analysis. By allowing adjustable robustness modulation, the proposed model enables more personalized and clinically adaptable treatment plans. These findings highlight the potential of interval analysis as a powerful tool for optimizing radiotherapy outcomes, balancing treatment efficacy and patient safety.

Skull base osteoradionecrosis: from pathogenesis to treatment.

This review aims to provide a comprehensive analysis of skull base osteoradionecrosis (ORN), a severe and rare complication of radiotherapy for head and neck malignancies. It explores pathogenesis, clinical presentation, diagnostic strategies, and management approaches, emphasizing the importance of multidisciplinary care in addressing this challenging condition. Skull base ORN results from radiotherapy-induced tissue damage, characterized by hypovascularity, hypoxia, and necrosis, often compounded by secondary infections. Advances in radiotherapy techniques, such as intensity-modulated radiotherapy and heavy particles, have reduced ORN incidence, though cases persist, particularly in high-dose radiotherapy fields. Emerging treatments, including hyperbaric oxygen therapy and the pentoxifylline-tocopherol protocol, show promise but lack robust evidence for standardized use. Surgical interventions, especially those incorporating vascularized tissue reconstruction, have demonstrated favorable outcomes in refractory cases. Recent studies underscore the utility of multimodal imaging techniques, including MRI and PET/CT, for distinguishing ORN from tumor recurrence. Skull base ORN represents a complex and potentially life-threatening condition requiring tailored, multidisciplinary management. Although advancements in diagnostics and therapeutics have improved outcomes, significant challenges remain, particularly in developing standardized protocols. Further research is needed to refine treatment strategies and improve evidence-based practices for this entity.

A prognostic and predictive model based on deep learning to identify optimal candidates for intensity-modulated radiotherapy alone in patients with stage II nasopharyngeal carcinoma: A retrospective multicenter study.

To develop and validate a prognostic and predictive model integrating deep learning MRI features and clinical information in patients with stage II nasopharyngeal carcinoma (NPC) to identify patients with a low risk of progression for whom intensity-modulated radiotherapy (IMRT) alone is sufficient. This multicenter, retrospective study enrolled 999 patients with stage II NPC from two centers. 3DResNet was used to extract deep learning MRI features and eXtreme Gradient Boosting model was employed to integrate the pre-trained features and clinical information to obtain an overall score for each patient. Based on the optimal cutoff value of the overall score, patients were stratified into high- and low- risk groups. Model performance was evaluated using concordance indexes (C-indexes), the area under the curve (AUC) values and calibration tests. Survival curves were used to analyze the clinical benefits of additional chemotherapy in each risk group. The combined model achieved a concordance index of 0.789 (95 % confidence interval [CI] 0.787-0.791), 0.768 (95 % CI 0.764-0.771), and 0.804 (95 % CI 0.801-0.807) for the training, internal validation, and external test cohorts, respectively, demonstrating a statistically significant improvement compared to the MRI model, T Stage, and N Stage. An overall score of < 0.405 in patients was significantly associated with a low risk of progression. In the low-risk group, patients treated with IMRT alone had comparable or even superior progression-free survival (PFS) compared to those who received additional chemotherapy. The model demonstrated a satisfactory prognostic and predictive performance for PFS. Patients with stage II NPC were stratified into different risk groups to help identify optimal candidates who could benefit from IMRT alone.

Identification and validation of a prognostic risk model based on radiosensitivity-related genes in nasopharyngeal carcinoma.

Despite advancements with intensity-modulated radiation therapy (IMRT), about 10 % of nasopharyngeal carcinoma (NPC) patients remain resistant to radiotherapy, leading to recurrence and poor prognosis. This study aims to identify radiosensitivity-related genes in NPC and develop a prognostic model to predict patient outcomes. We analyzed 179 NPC samples from Fujian Cancer Hospital using RNA sequencing. Differentially expressed genes (DEGs) were identified between radiotherapy-sensitive and resistant samples. Machine learning algorithms and Cox regression were used to construct a prognostic risk model, validated in the GSE102349 dataset. Additional analyses included functional pathway, immune infiltration, and drug sensitivity. A risk model based on six genes (LCN8, IGSF1, RIMS2, RBP4, TBX10, ETV4) was developed. Kaplan-Meier analysis showed significantly shorter progression-free survival (PFS) in the high-risk group. The model's AUC values were 0.872, 0.807, and 0.802 for 1-year, 3-year, and 5-year predictions. A nomogram including clinical factors was created, and enrichment analysis linked the high-risk group to radiotherapy resistance mechanisms. This study established a novel radiosensitivity-related prognostic model, offering insights into NPC prognosis and radiotherapy resistance mechanisms.

Differences in superficial dose distribution in patients receiving intensity modulated radiotherapy (IMRT) after radical mastectomy

Differences in superficial dose distribution in patients receiving intensity modulated radiotherapy (IMRT) after radical mastectomy

Dosimetric and Radiobiological Impact of Patient Setup Errors in Intensity-modulated Radiotherapy for Esophageal Cancer.

To evaluate the impact of patient setup errors on the dosimetry and radiobiological models of intensity-modulated radiotherapy (IMRT) for esophageal cancer. This retrospective study with 56 patients in thermoplastic mask (TM) and vacuum bag (VB) groups utilized real setup-error (RSE) data from cone-beam CT scans to generate simulated setup-error (SSE) data following a normal distribution. The SSE data were applied to simulate all treatment fractions per patient by shifting the plan isocenter and recalculating the dose. A simulated plan sum (SPS) was created by accumulating all simulated fraction plans. Comparisons of target dose, improved homogeneity index (iHI), conformity index (CI), tumor control probability (TCP) and normal tissue complication probability (NTCP) were conducted between SPSs and original treatment plans (OTPs). Correlations between RSE and TCP/NTCP were analyzed. Compared to OTPs in the TM group, the planning target volume (PTV) of SPSs showed reductions in D95%, D98%, iHI, CI and TCP by 1.2%, 2.2%, 2.3%, 7.3% and 1.2%, while D2% increased by 0.3%; D2% of clinical target volume (CTV) increased by 0.2% (P < .05). In the VB group, D95%, D98%, iHI, CI and TCP of PTV decreased by 2.5%, 4.5%, 4.2%, 15.6% and 2.0%, with D2% increasing by 0.5%; D2% of CTV increased by 0.5% while D98% decreased by 0.2% (P < .05). The dose of organs at risk (OARs) changed slightly in both groups. The mean and standard deviation of absolute RSE negatively correlated with the TCP of PTV, while the mean RSE positively correlated with the NTCP of lung and spinal cord. Setup errors may reduce dose homogeneity and conformity, potentially reducing TCP of PTV and increasing NTCP, especially when mean RSE shifts the isocenter towards OARs. VB immobilization may result in relatively larger impacts of setup errors, but this needs future validation.

Neoadjuvant Chemoradiotherapy Using Moderately Hypofractionated Intensity-Modulated Radiotherapy Versus Upfront Surgery for Resectable Pancreatic Cancer: A Retrospective Cohort Study.

The efficacy of neoadjuvant chemoradiotherapy for resectable pancreatic ductal adenocarcinoma (R-PDAC) remains unclear. This study was designed to evaluate neoadjuvant chemoradiotherapy by using intensity-modulated radiotherapy (NAC-IMRT) for R-PDAC compared with upfront surgery (UpS). Among 198 patients with R-PDAC who were indicated for resection between 2013 and 2021, 130 were included in this study after excluding patients who underwent neoadjuvant chemotherapy and did not meet the NAC-IMRT criteria (Eligible set). NAC-IMRT was planned for 58 patients, and UpS was planned for 72 patients. Additionally, in 105 patients who could undergo the planned treatment (As-treated set), the surgical, pathological, and oncological outcomes were evaluated. In the Eligible set, median overall survival (OS) was 50.5 months with NAC-IMRT and 34.7 months with UpS and progression-free survival was 20.4 months with NAC-IMRT and 13.9 months with UpS. In the As-treated set, OS was longer in the NAC-IMRT group (66.7 months vs. 34.7 months, p = 0.007). On multivariate analysis, NAC-IMRT was identified as an independent factor for better OS (hazard ratio 0.617, 95% confidence interval 0.382-0.995, p = 0.047, in the Eligible set). The incidence of postoperative complications did not show a difference between the two groups, and NAC-IMRT suppressed local tumor invasion, including lymphatic, venous, perineural invasion, and lymph node metastases. NAC-IMRT may offer superior survival outcomes and manageable toxicity in R-PDAC patients compared with upfront surgery. This study supports the efficacy and safety of NAC-IMRT and recommends its consideration in R-PDAC treatment protocols.

Multi-Institutional Phase II Study on the Efficacy and Safety of Dynamic Tumor-Tracking, Moderately Hypofractionated Intensity-Modulated Radiotherapy in Patients With Locally Advanced Pancreatic Cancer.

For delivering high radiation doses to pancreatic tumors, organ motion management is indispensable; however, studies on this are limited. We aimed to evaluate the efficacy and safety of dynamic tumor tracking (DTT) moderately hypofractionated intensity-modulated radiotherapy (IMRT) in patients with locally advanced pancreatic cancer (LAPC). Patients with histological confirmation for LAPC were included. A linac system, which was mounted with a gimbal function, was used for DTT-IMRT. The prescribed dose was 48 Gy in 15 fractions. The primary endpoint was the 1-year rate of freedom from locoregional progression (FFLP). DTT-IMRT was successfully administered in 25 patients enrolled from four institutions. The median range of respiratory motion during DTT-IMRT was 9.8 mm (range: 3.5-27.3 mm), and the median tracking accuracy was 2.6 mm (range: 0.7-5.2 mm). With a median follow-up period of 13.9 months, the 1-year FFLP rate was 75.3% (lower limit of one-sided 80% confidence interval [CI]: 60.2%), which satisfied the predetermined primary endpoint. One-year locoregional progression-free survival, progression-free survival, and overall survival were 56.0% (95% CI: 34.8%-72.7%), 44.0% (95% CI: 24.5%-61.9%), and 60.0% (95% CI: 38.4%-76.1%), respectively. Regarding nonhematologic toxicities, grade 3 acute gastrointestinal (GI) toxicity was observed in two patients (8%), and two patients (8%) each experienced grade 3 late GI and non-GI toxicities. No grade 4 or 5 nonhematologic toxicities were observed. DTT moderately hypofractionated IMRT shows preferable locoregional control without significant toxicity in patients with LAPC. UMIN000017521.

Efficacy of hydrogel spacer compared with intensity-modulated radiotherapy for 3-dimensional conformal radiotherapy for prostate cancer.

One major adverse effect of prostate radiotherapy is associated with the rectum. The SpaceOAR system has been developed to address this problem, as it enables treatment planning with a reduced dose to the rectum. This study aimed to evaluate and compare the treatment plans between three-dimensional conformal radiotherapy (3D-CRT) and volumetric modulated arc therapy (VMAT) for prostate cancer using the SpaceOAR system. Thirty-five patients treated with prostate cancer radiation using the SpaceOAR system received a total radiation dose of 60 Gy/20 fractions. The dose constraints and robustness of the plan for VMAT and 3D-CRT were compared. For 3D-CRT, 6-field conformal method and 2-arc conformal method were created and compared in 3 treatment plans together with VMAT. The dose-constraint evaluation was performed using the planning target volume (PTV), rectum (mean dose), bladder (mean dose), and femoral head (mean dose). One issue associated with prostate radiotherapy is the physiological movement of the target prostate gland, which reduces the accuracy of irradiation. The prostate moves several millimeters during irradiation due to physiological movements, and there are reports of a decrease in the PTV index due to this effect. This has a significant impact on the cure rate of prostate cancer. A comparative study of the 3 irradiation methods was conducted to investigate this issue. Each study item was analyzed using the Friedman test to determine the significance of the 3 irradiation methods. Our analysis showed that the dose constraint was statistically significant for VMAT, but 3D-CRT was also sufficient in achieving dose constraints. The hydrogel spacer reduced the rectal dose and improved the dose-constrained fulfillment rate in VMAT and 3D-CRT. In a study of prostate motion during irradiation, 3D-CRT, a robust plan, was superior in the PTV mean evaluation over VMAT, where the multileaf collimator moved in fine increments. VMAT is currently the standard treatment for prostate cancer; however, with the introduction of the SpaceOAR system using hydrogel spacers, 3D-CRT may also be a viable option for prostate cancer treatment.

Dose-volume constraints for severe acute gastrointestinal toxicity in cervical cancer patients receiving extended-field intensity-modulated radiotherapy and concurrent chemotherapy

Dose-volume constraints for severe acute gastrointestinal toxicity in cervical cancer patients receiving extended-field intensity-modulated radiotherapy and concurrent chemotherapy

Hypofractionated partial breast irradiation after breast-conserving surgery for patients with early stage breast cancer in China Mainland: a single-arm prospective trial

To report the results of a single-arm, prospective partial breast irradiation (PBI) trial from China mainland using a dose of 40.05 Gy in 15 fractions delivered with intensity-modulated radiation therapy (IMRT) technique for patients with early stage breast cancer. Patients aged ≥ 50 years who underwent breast-conserving surgery for unifocal non-lobular invasive breast cancer, with pathological T1 disease, clear margins, negative axillary nodes, and positive hormonal receptors, were recruited. The primary endpoint was 3-year cosmetic deterioration, and secondary endpoints included adverse events, ipsilateral breast tumor recurrence (IBTR), regional recurrence, and survivals. This trial is registered with ClinicalTrials.gov (registration No. NCT03411174). From Jan of 2015 to July of 2018, 208 out of 222 patients recruited were evaluable and included in final analysis. The median follow-up was 66.3 (range: 42.0-105.4) months. The 3-year overall cosmetic deterioration rate was 3.5%. The rates of grade 2 radiation dermatitis and breast induration was 5.8% and 1.5%, respectively. No one experienced ≥ grade 2 breast pain, edema, or telangiectasia. The 5-year cumulative incidence of IBTR and RR was 0.5%. No one developed DM. The 5-year DFS was 99.0%. Four patients died from non-breast cancer causes, and the 5- year OS was 97.9%. In conclusion, we observed lower rates of cosmetic deterioration, IBTR, and ≥ grade 2 acute/late normal tissue effects following PBI with a moderately hypofractionated regimen delivered with IMRT technique. Therefore, this regimen represents an attractive option when an external beam PBI approach is chosen to treat a patient with low-risk early breast cancer.

Automating the optimization of proton PBS treatment planning for head and neck cancers using policy gradient-based deep reinforcement learning.

Proton pencil beam scanning (PBS) treatment planning for head and neck (H&N) cancers is a time-consuming and experience-demanding task where a large number of potentially conflicting planning objectives are involved. Deep reinforcement learning (DRL) has recently been introduced to the planning processes of intensity-modulated radiation therapy (IMRT) and brachytherapy for prostate, lung, and cervical cancers. However, existing DRL planning models are built upon the Q-learning framework and rely on weighted linear combinations of clinical metrics for reward calculation. These approaches suffer from poor scalability and flexibility, that is, they are only capable of adjusting a limited number of planning objectives in discrete action spaces and therefore fail to generalize to more complex planning problems. Here we propose an automatic treatment planning model using the proximal policy optimization (PPO) algorithm in the policy gradient framework of DRL and a dose distribution-based reward function for proton PBS treatment planning of H&N cancers. The planning process is formulated as an optimization problem. A set of empirical rules is used to create auxiliary planning structures from target volumes and organs-at-risk (OARs), along with their associated planning objectives. Special attention is given to overlapping structures with potentially conflicting objectives. These planning objectives are fed into an in-house optimization engine to generate the spot monitor unit (MU) values. A decision-making policy network trained using PPO is developed to iteratively adjust the involved planning objective parameters. The policy network predicts actions in a continuous action space and guides the treatment planning system to refine the PBS treatment plans using a novel dose distribution-based reward function. A total of 34 H&N patients (30 for training and 4 for test) and 26 liver patients (20 for training, 6 for test) are included in this study to train and verify the effectiveness and generalizability of the proposed method. Proton H&N treatment plans generated by the model show improved OAR sparing with equal or superior target coverage when compared with human-generated plans. Moreover, additional experiments on liver cancer demonstrate that the proposed method can be successfully generalized to other treatmentsites. The automatic treatment planning model can generate complex H&N plans with quality comparable or superior to those produced by experienced human planners. Compared with existing works, our method is capable of handling more planning objectives in continuous action spaces. To the best of our knowledge, this is the first DRL-based automatic treatment planning model capable of achieving human-level performance for H&Ncancers.

Neurocognitive impact of different irradiation modalities for patients with grade I-II skull base meningioma: a prospective multi-arm cohort study (CANCER COG)

BackgroundRadiotherapy as a complement or an alternative to neurosurgery has a central role in the treatment of skull base grade I-II meningiomas. Radiotherapy techniques have improved considerably over the last two decades, becoming more effective and sparing more and more the healthy tissue surrounding the tumour. Currently, hypo-fractionated stereotactic radiotherapy (SRT) for small tumours and normo-fractionated intensity-modulated radiotherapy (IMRT) or proton-therapy (PT) for larger tumours are the most widely used techniques. It is expected a decrease of the risk of cognitive impairment with these modern techniques. However prospective data about cognitive long-term consequences of partial brain irradiation with SRT, PT, or IMRT remain very scarce to date.MethodsCANCER COG is one of the first multicentric study in the world to prospectively assess the cognitive performances of patients following different modalities of cerebral radiotherapy (stereotactic radiotherapy, proton therapy, intensity modulated radiotherapy) for the treatment of grade I-II skull base meningioma, up to at least 10 years after the end of radiotherapy. This longitudinal study includes the follow-up of 3 cohorts, including: patients treated with PRT, IMRT, and SRT. An additionally control group will be formed. The primary objective is to report long-term cognitive deterioration in each cohort until 10 years after the end of irradiation. The rate of clinical symptomatology improvement over time after irradiation, the evolution of health-related quality-of-life, anxiety/depression, fatigue, over time after irradiation, the tumoral local control after irradiation, the progression-free survival (PFS), the professional reintegration for working-age patients will also be assessed. CANCER COG aims to help clinicians to choose the best irradiation techniques with the best benefit/risk ratio. Inclusions started on september 2023.Trial registrationThe study was registered on clinicaltrials.gov with the following number: NCT 06036706.

Photon mini-GRID therapy for preoperative breast cancer tumor treatment: A treatment plan study.

Breast cancer is the leading cause of female cancer mortality worldwide, accounting for 1 in 6 cancer deaths. Surgery, radiation, and systemic therapy are the three pillars of breast cancer treatment, with several strategies developed to combine them. The association of preoperative radiotherapy with immunotherapy may improve breast cancer tumor control by exploiting the tumor radio-induced immune priming. However, this requires the use of hypofractionated radiotherapy (3×8Gy), increasing the risk of toxicity. Mini-GRID therapy (mini-GRT) is an innovative form of spatially fractionated radiation therapy (SFRT) characterized by narrow beam widths between 1 to 2mm that promises a significant increase in normal tissue dose tolerances and could thereby represent a new alternative for preoperative breast cancer treatment. Mini-GRT has been successfully implemented at the Hospital de Santiago de Compostela (Spain) with a flattening filter-free LINAC (megavoltage x-rays). In this dosimetry proof-of-concept study, we evaluate the feasibility of photon mini-GRT for preoperative breast cancer treatment. We also assess the clinical potential of mini-GRT and compare it with the current treatment standard of intensity-modulated radiotherapy (IMRT). Seven unbiased breast cancer dosimetries of patients treated with stereotactic body radiotherapy (SBRT) (3×8Gy, IMRT) were selected for the study. Photon mini-GRT was compared with SBRT using three main criteria: (i) the dose to organs at risk (OARs), (ii) the dose constraints dictated by normal tissue tolerance, and (iii) the lateral penumbra in OARs. Tumor coverage was evaluated in terms of normalized total dose at 8Gy-fractions. The optimized SBRT by IMRT was realized at the Institut Curie, Paris, France. The dose in mini-GRT was calculated by means of Monte Carlo simulations based on the mini-GRT implementation realized at the University Hospital in Santiago de Compostela. Compared to SBRT plans, mini-GRT resulted in a reduction of the mean dose to the lungs, heart, chest wall, and lymph nodes in the studied cases by a factor ranging from 50% to 100%. Additionally, valley, mean, and peak doses to normal tissues meet the dose tolerance limits for the considered OARs, the most challenging of all being the skin. The mean dose to the skin was reduced (20%-60% less) for most of the studied cases. Mini-GRT also yielded sharper lateral penumbras in the skin and lungs (size reduced by at least 50%). Similar tumor integral doses were obtained for the two treatment modalities. Mini-GRT with megavoltage x-rays is an innovative treatment approach already implemented in a clinical context. In this proof-of-concept study, we evaluated mini-GRT for partial breast cancer irradiation, demonstrating its potential for preoperative treatment thanks to the high skin and normal tissue-sparing capabilities. These initial results represent a first step towards clinical use and encourage further prospective clinical studies.

Pretreatment FDG PET in prognosis of locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiation therapy

Pretreatment FDG PET in prognosis of locoregionally advanced nasopharyngeal carcinoma treated with intensity-modulated radiation therapy

Pulse-by-pulse treatment planning and its application to generic observations of ultra-high dose rate (FLASH) radiotherapy with photons and protons.

The exact temporal characteristics of beam delivery affect the efficacy and outcome of ultra-high dose rate (UHDR or "FLASH") radiotherapy, mainly due to the influence of the beam pulse structure on mean dose rate. Single beams may also be delivered in separate treatment sessions to elevate mean dose rate. This paper therefore describes a model for pulse-by-pulse treatment planning and demonstrates its application by making some generic observations of the characteristics of FLASH radiotherapy with photons and protons.&#xD;&#xD;Approach. A beam delivery model was implemented into the AutoBeam (v6.3) inverse treatment planning system, so that the individual pulses of the delivery system could be explicitly described during optimisation. The delivery model was used to calculate distributions of time-averaged and dose-averaged mean dose rate and the dose modifying factor for FLASH was then determined and applied to dose calculated by a discrete ordinates Boltzmann solver. The method was applied to intensity-modulated radiation therapy (IMRT) with photons as well as to passive scattering and pencil beam scanning with protons for the case of a simple phantom geometry with a prescribed dose of 36 Gy in 3 fractions.&#xD;&#xD;Main results. Dose and dose rate are highest in the target region, so FLASH sparing is most pronounced around the planning target volume. When using a treatment session per beam, OAR sparing is possible more peripherally. The sparing with photons is higher than with protons because the dose to OAR is higher with photons.&#xD;&#xD;Significance. The framework provides an efficient method to determine the optimal technique for delivering clinical dose distributions using FLASH. The most sparing occurs close to the PTV for hypofractionated treatments.&#xD.

Volumetric and Dosimetric Changes in Bladder and Rectum and Target During Intensity-Modulated Radiotherapy in Patients of Locally Advanced Carcinoma Cervix

Volumetric and Dosimetric Changes in Bladder and Rectum and Target During Intensity-Modulated Radiotherapy in Patients of Locally Advanced Carcinoma Cervix

A curative effect evaluation of intensity-modulated radiation therapy combined with periorbital triamcinolone acetonide injection in treating thyroid eye disease patients with active extraocular muscle but low CAS

The purpose of this study is to evaluate the effectiveness of intensity-modulated radiation therapy (IMRT) combined with periorbital triamcinolone acetonide injection in treating thyroid eye disease (TED) patients with active extraocular muscle but low CAS. The retrospective observational study was conducted. A total of 156 eligible patients were selected from the TED patient database of the Ophthalmology Department of West China Hospital of Sichuan University. The patient’s relevant medical history was recorded, including gender, age of initial onset, onset eye, the interval between onset and the first visit to our hospital, extraocular muscle condition, smoking status, CAS, NOSPECS, thyroid function, symptoms and signs, and the condition of the affected extraocular muscle. We found that IMRT combined with periorbital triamcinolone acetonide injection has a good therapeutic effect on TED patients with low CAS but significant active extraocular muscles, and there is a significant improvement at 3 months after treatment. Thyroid function and CAS can affect the curative effect of IMRT. Patients with hyperthyroidism had worse effect than those with normal thyroid function. The higher the CAS, the better the effect.

Postoperative Radiotherapy ± Cetuximab for Intermediate-Risk Head and Neck Cancer.

Radiotherapy (RT)/cetuximab (C) demonstrated superiority over RT alone for locally advanced squamous head and neck cancer. We tested this in completely resected, intermediate-risk cancer. Patients had squamous cell carcinoma of the head and neck (SCCHN) of the oral cavity, oropharynx, or larynx, with one or more risk factors warranting postoperative RT. Patients were randomly assigned 1:1 to intensity-modulated RT (60-66 Gy) with once-per-week C or RT alone. The primary hypothesis was that RT + C would improve overall survival (OS) in randomly assigned/eligible patients, with a prespecified secondary plan to test this in the human papillomavirus (HPV)-negative subpopulation. Disease-free survival (DFS) and toxicity were secondary end points. OS and DFS were tested via stratified log-rank test; toxicity was compared via Fisher's exact test. We enrolled 702 patients from November 2009 to March 2018; 577 were randomly assigned/eligible. Most (63.6%) had oral cavity cancer and most (84.6%) had high epidermal growth factor receptor expression. There were fewer deaths (184) than expected. OS (median follow up, 7.2 years) was not significantly improved (hazard ratio [HR], 0.81; one-sided P = .0747; 5-year OS 76.5% v 68.7%), but DFS was (HR, 0.75; one-sided P = .0168; 5-year DFS 71.7% v 63.6%). Benefit of RT + C was only seen in the HPV-negative subpopulation (80.2% of patients in the trial). Grade 3-4 acute toxicity rates were 70.3% (RT + C) versus 39.7% (RT; two-sided P < .0001), mostly skin and/or mucosal effects. Late grade ≥3 toxicity rate was 33.2% (RT + C) versus 29.0% (RT; two-sided P = .3101). There were no grade 5 toxicities in either arm. RT + C significantly improved DFS, but not OS, with no increase in long-term toxicity, compared with RT alone for resected, intermediate-risk SCCHN. RT + C is an appropriate option for carefully selected patients with HPV-negative disease.