Reirradiation of squamous cell carcinoma of the head and neck with external photons: A practical review of the literature.

The modalities of management by reirradiation for recurrence or a second localization of head and neck squamous cell carcinoma (HNSCC) in previously irradiated terrain is challenging due to the great heterogeneity of data in the literature, mainly retrospective data reporting non-negligible risks of serious late toxicity events. With the recent development of more precise and conformal radiotherapy techniques such as intensity modulated radiotherapy (IMRT), volumetric modulated arc therapy (VMAT), stereotactic radiotherapy (SBRT), the benefit-to-risk ratio of reirradiation has evolved in recent years with encouraging results, but patient selection is crucial. The aim of this review is to discuss the role of HNSCC reirradiation in terms of patient selection and external photon radiotherapy techniques for definitive tumor reirradiation and postoperative reirradiation.

Recurrence pattern of glioblastoma treated with intensity-modulated radiation therapy versus three-dimensional conformal radiation therapy.

PURPOSE: To evaluate recurrence patterns of and survival outcomes in glioblastoma treated with intensity-modulated radiation therapy (IMRT) versus three-dimensional conformal radiation therapy (3D-CRT). MATERIALS AND METHODS: We retrospectively examined 91 patients with glioblastoma treated with either IMRT (n = 60) or 3D-CRT (n = 31) between January 2013 and December 2019. Magnetic resonance imaging showing tumor recurrence and planning computed tomography scans were fused for analyzing recurrence patterns categorized as in-field, marginal, and out-of-field based on their relation to the initial radiation field. RESULTS: The median overall survival (OS) was 18.9 months, with no significant difference between the groups. The median progression-free survival (PFS) was 9.4 months, with no significant difference between the groups. Patients who underwent gross total resection (GTR) had higher OS and PFS than those who underwent less extensive surgery. Among 78 relapse cases, 67 were of in-field; 5, marginal; and 19, out-of-field recurrence. Among 3D-CRT-treated cases, 24 were of in-field; 1, marginal; and 9, out-of-field recurrence. Among IMRT-treated cases, 43 were of in-field; 4, marginal; and 10, out-of-field recurrence. In partial tumor removal or biopsy cases, out-of-field recurrence was less frequent in the IMRT (16.2%) than in the 3D-CRT (36.3%) group, with marginal significance (p = 0.079). CONCLUSION: IMRT and 3D-CRT effectively managed glioblastoma with no significant differences in OS and PFS. The survival benefit with GTR underscored the importance of maximal surgical resection. The reduced rate of out-of-field recurrence in IMRT-treated patients with partial resection highlights its potential utility in cases with unfeasible complete tumor removal.

Investigation of the distribution of inguinal lymph nodes and delineation of the inguinal clinical target volume using 18F-FDG PET/CT.

OBJECTIVE: Radiotherapy is a crucial treatment modality for pelvic cancers, but uncertainties persist in defining the clinical target volume (CTV) for the inguinal lymphatic drainage region. Suboptimal CTV delineation may compromise treatment efficacy and result in subpar disease control. This study aimed to investigate and map the distribution of lymph node metastases (LNM) in the groin area to facilitate an improved and detailed CTV definition using 18F-fluorodeoxyglucose positron emission tomography/computed tomography (18F-FDG PET/CT). METHODS: Inguinal LNM in patients with biopsy-proven pelvic malignancies were identified using 18F-FDG PET/CT scan. The longitudinally nearest axial plane was determined based on six typical bony landmarks, and the axial direction relative to the femoral artery of LNM was recorded. The distances from the LNM to the nearest edge of the femoral artery were measured on the axial plane. An optimal margin to cover 95% of LNM was estimated to develop contouring recommendations. RESULTS: In this study, 500 positive LNM were identified by 18F-FDG PET/CT among 185 patients with primary pelvic malignancies. Relative to the femoral artery, lymph nodes were distributed laterally (10:00-11:00, n = 35), anteriorly (12:00-1:00, n = 213), and medially (2:00-4: 00, n = 252). For CTV delineation, the recommended distances from the femoral artery on the SFH were lateral 19 mm, anterior 19 mm, and medial 25 mm; on the SGT were lateral 26 mm, anterior 20 mm, and medial 25 mm; on the SPS were lateral 28 mm, anterior 29 mm, and medial 26 mm; on the IPS were anterior 29 mm and medial 28 mm; on the IIT were anterior 27 mm and medial 27 mm; on the ILT were anterior 25 mm and medial 23 mm. Use interpolation to contour the area between six axial slices, including any radiographically suspicious LNM. CONCLUSIONS: Using 18F-FDG PET/CT, we investigated the distribution pattern of inguinal LNM and propose a more comprehensive guideline for inguinal CTV delineation.

Current situation and trends of radiation therapy in Japan based on the National Database Open Data.

This study aimed to visualize the current situation and trends in radiation therapy in Japan using open data from the Japanese National Database of Health Insurance Claims and Specific Health Checkups (NDB). We downloaded the NDB open data from the website of Japan's Ministry of Health, Labor and Welfare and used Python libraries to analyze the receipt data related to radiation therapy from fiscal year 2014 to 2022. The number of radiation therapy plans peaked in 2019, temporarily declined and subsequently showed a gradual increase. Conversely, the total points associated with radiation therapy have consistently increased without any decline. The use of high-precision radiation therapies such as intensity-modulated radiation therapy (IMRT) has increased over time. Significant regional differences exist, with the Chubu and Kyushu regions showing higher total points and receipts per certified radiation oncologist. A correlation was observed between the number of IMRT plans per population and the number of certified radiation oncologists. Males exhibited a sharp peak in their early 70s, while females demonstrated a mild peak from their 40s to 80s. In recent years, the points for males in their early 70s have rapidly increased. We used the NDB open data to illustrate the current situation and trends in radiation therapy in Japan, highlighting reduced costs and workloads. This study underscored the regional differences in radiation therapy and emphasized the need to discuss strategies for meeting future demand.

Weekly Image Guidance in Patients With Cervical Cancer Treated With Intensity-Modulated Radiation Therapy: Results of a Large Cohort Study.

BACKGROUND: Image guidance is recommended for patients undergoing intensity-modulated radiation therapy (IMRT) for cervical cancer. In this study, we evaluated the feasibility of a weekly image guidance pattern and analyzed the long-term outcomes in a large cohort of patients. METHODS: The study enrolled patients with Stage IB-IVA cervical cancer who received definitive radiotherapy or concurrent chemoradiotherapy. IMRT was delivered at a dose of 50.4 Gy in 28 fractions, with weekly cone-beam computed tomography (CBCT). Physicians advised patients on rectum and bladder preparation to help them prepare on nonimaging guidance days. When significant tumor regression was observed, a second computed tomography simulation and replanning were performed. RESULTS: The median follow-up periods were 63.4 months. The incidence rates of loco-regional and distant failure were 9.9% and 13.6%. The 5-year overall survival (OS), disease-free survival (DFS), loco-regional relapse-free survival (LRFS), and distant metastasis-free survival (DMFS) rates were 80.1%, 72.9%, 78.3%, and 74.8%, respectively. For patients with different stages, the 5-year OS, DFS, LRFS, and DMFS rates were statistically significant. For patients with and without positive regional lymph nodes, the 5-year OS, DFS, LRFS, and DMFS rates were 64.5% and 86.0%, 56.8% and 78.8%, 62.7% and 84.3%, and 58.8% and 81.0%, respectively. Multivariate analysis showed that age, histology, tumor size, cancer stage, pretreatment squamous cell carcinoma antigen level, and para-aortic metastatic lymph nodes were independent prognostic factors of OS. Fifty-six (4.0%) patients experienced late Grade 3/4 chronic toxicities. CONCLUSIONS: IMRT with weekly CBCT is an acceptable image guidance strategy in countries with limited medical resources.

Setting the Stage: Feasibility and Baseline Characteristics in the PARTIQoL Trial Comparing Proton Therapy vs. IMRT for Localized Prostate Cancer.

PURPOSE/OBJECTIVES: Men with localized prostate cancer may receive either photon-based intensity-modulated radiotherapy (IMRT) or proton beam therapy (PBT). The XXXXX trial (NCT01617161), demonstrates the feasibility of performing a large, multicenter phase 3 randomized trial comparing IMRT to PBT for localized prostate cancer. Here, we report baseline features of patients enrolled on this trial and present strategies to improve feasibility of other similar trials. MATERIALS/METHODS: Patients with low- or intermediate-risk prostate cancer were randomized to either PBT or IMRT with stratification by institution, age, use of rectal spacer, and fractionation schedule (conventional fractionation: 79.2 Gy in 44 fractions vs. moderate hypofractionation: 70.0 Gy in 28 fractions). The primary endpoint is a change from baseline bowel health using the EPIC score 24 months after radiotherapy. Secondary objectives include treatment-related differences in urinary and erectile functions, adverse events, and efficacy endpoints. RESULTS: Between 07/2012 and 11/2021, 450 patients were successfully accrued. Patients were randomized to either PBT (N=226) or to IMRT (N=224); 13 were ineligible or withdrew prior to treatment. The median age of 437 analyzed patients was 68 years (range 46-89). 41% of patients had low-risk and 59% had intermediate-risk disease. 49% of patients were treated with conventional fractionation and 51% with moderately hypofractionation. For patients receiving PBT, 48% used a rectal balloon, 44% a rectal spacer, and 5% both. For patients receiving IMRT, 46% used a rectal balloon, 42% a rectal spacer, and 5% both. PBT and IMRT arms were balanced for baseline variables. CONCLUSIONS: Despite significant challenges, the XXXXX trial demonstrated that, with targeted recruitment approaches, multicenter collaboration, payer engagement, and protocol updates to incorporate contemporary techniques, it is feasible to perform a large phase III randomized clinical trial to assess whether PBT improves outcomes. We will separately report primary results and continue to monitor participants for longer followup and secondary endpoints.

A Four-dimensional Computed Tomography Generated Internal Target Volume Approach to Paediatric High Risk Neuroblastoma to Reduce Organ at Risk and Normal Tissue Irradiation.

AIMS: The magnitude of upper abdominal organ motion in children may be overestimated by current planning target volumes (PTV). A four-dimensional computed tomography (4DCT) - derived internal target volume (ITV) is frequently used in adult radiotherapy to take respiratory-related organ motion into account. In this study, the dosimetric consequences for target coverage and organs at risk from the use of an ITV approach compared to standard PTV margins in children with high-risk neuroblastoma were investigated. MATERIALS AND METHODS: 14 patients, median age 4.1 years, range 1.5 - 18.9 years, (9 midline targets, 5 lateralised) each had two dual arc volumetric modulated arc therapy (VMAT) plans (14 ×1.5 Gy) generated. One used an ITV-approach; motion information derived from 4DCT (PTV_itv) with a 5mm ITV to PTV expansion, and the other a PTV margin of 10mm from CTV to PTV (PTV_standard). Differences in absolute PTV volume and organ at risk doses are described. RESULTS: The ITV approach resulted in a highly significant reduction in PTV size of 38% (p<0.0001). For midline targets, an ITV approach resulted in a small but statistically significant reduction in combined mean kidney dose of 0.8Gy, p 0.01. Mean heart and lung dose were reduced by an average of 1 Gy with an ITV approach. Non-PTV integral dose from 30.4 Gy L to 27.8 Gy L using an ITV approach. CONCLUSION: An ITV-approach to respiratory related organ motion management in children can significantly reduce absolute PTV volumes, maintain target coverage and reduce dose delivered to normal tissue in proximity to the target. This is an essential step to maximising the benefits of highly conformal radiotherapy techniques including VMAT for this patient group, and in the future with Proton Therapy.

Inter-fraction motion robustness in a prospective phase II trial on dose-escalated proton reirradiation for locally recurrent rectal cancer.

Background and purpose: Intensity modulated proton therapy (IMPT) enables generation of conformal dose plans with organ at risk (OAR) sparing potential. However, pelvic IMPT robustness is challenged by inter-fraction motion caused by constant anatomical variations. In this study, the dosimetric impact of inter-fraction motion on target coverage and dose to OAR was quantified in the prospective phase II study ReRad-II on dose-escalated proton reirradiation for locally recurrent rectal cancer (LRRC). Materials and methods: The inter-fraction motion robustness was assessed for the initial twelve patients enrolled in the ReRad-II study. Patients with resectable LRRC were assessed for neoadjuvant IMPT (55 Gy(RBE)/44Fx) and unresectable recurrences for definitive IMPT (57.5-65 Gy(RBE)/ 46-52Fx). Target coverage and dose to OAR were assessed for robustly optimised three-field IMPT, on 12 plan computerized tomography (CT) scans (pCT) - and 47 repetitive control CT scans (cCTs) during the treatment. The target coverage and doses to OAR were re-calculated on each cCT and the mean dose ratio (pCT/cCT-ratio) and target coverage (V95%) was evaluated. Results: The target coverage was robust with a mean dose pCT/cCT-ratio of 1.00 (+/-1%). The V95% target coverage for every cCT were above the accepted worst-case scenario in the robust evaluation. Considerable variation in bladder-, bowel bag-, and bowel loop volume was observed. The OAR with the largest variation in ratio was the bladder (pCT/cCT-ratio: 1.3 (range: 0.5-4.7). Conclusions: IMPT for dose-escalated reirradiation of LRRC provided anatomically robust target coverage despite OAR changes. Inter-fraction motion resulted in OAR doses varying within clinically acceptable range.

Explore the feasibility of using spot-scanning proton arc therapy for a synchrotron accelerator-based proton therapy system - A simulation study.

OBJECTIVE: The aim of this study was to evaluate the feasibility and plan quality of spot-scanning proton arc therapy (SPArc) using a synchrotron-accelerator-based proton therapy system compared to intensity-modulated proton therapy (IMPT). APPROACH: Five representative disease sites, including head and neck, lung, liver, brain chordoma, and prostate cancers, were retrospectively selected. Both IMPT and SPArc plans are generated with the HITACHI ProBEAT PBS system's minimum MU constraints and physics beam model. The SPArc plans are generated with 2.5° sampling frequency. The static delivery time was simulated based on the previously published synchrotron delivery sequence model, and the dynamic delivery time was simulated using a proton arc gantry mechanical model integrated with the synchrotron delivery sequence. Both dosimetric plan quality and delivery efficiency are evaluated. MAIN RESULTS: A superior plan quality is reached compared with the IMPT plans generated for the same disease site. However, a relatively prolonged static and dynamic delivery time post new challenge, as static time increased by 49.22% and dynamic time 59.10% on average. SIGNIFICANCE: This study presents the first simulation results of delivering the SPArc plans using a synchrotron-accelerated proton therapy system. The result shows its feasibility and limitations, which could guide future development.

Clinical advantages of incorporating predicted weekly anatomy in IMPT optimization with reduced setup error.

BACKGROUND: In head and neck (H&N) cancer treatment, a conventional setup error (SE) of 3mm is often used in robust optimization (cRO3mm). However, cRO3mm may lead to excessive radiation doses to organs at risk (OARs) and does not purposefully compensate for interfractional anatomy variations. PURPOSE: This study introduces a method using predicted images from an anatomical model and a reduced 1mm SE uncertainty for robust optimization (aRO1mm), aiming to decrease the dose to OARs without affecting the coverage of the clinical target volume (CTV). METHODS: This retrospective study involved 10 nasopharynx radiotherapy patients. Validation CT scans (vCT) from treatment weeks 1 to 6 were analyzed. A predictive anatomical model, designed to capture the average anatomical changes over time, provided predicted CT images for weeks 1, 3, and 5. We compared three optimization scenarios: (1) aRO1mm, using three predicted images with 1mm setup shift and 3% range uncertainty, (2) cRO3mm, with a robust 3mm setup shift and 3% range uncertainty, and (3) cRO1mm, a robust 1mm setup shift and 3% range uncertainty. The accumulated dose to CTVs and serial organs was evaluated under these uncertainties, while parallel OARs were assessed using the accumulated nominal dose (without errors). RESULTS: The accumulated volume receiving 94% of the prescribed dose (V94) for CTVs in cRO3mm exceeded 98%, meeting the clinical goal. For high-risk CTV, the minimum V94 was 96.44% in aRO1mm and 94.05% in cRO1mm. For low-risk CTV, these values were 97.68% in aRO1mm and 97.15% in cRO1mm. When comparing aRO1mm to cRO3mm on OARs, aRO1mm reduced normal tissue complication probability (NTCP) for grade ≥ $\ge$ 2 xerostomia and dysphagia by averages of 3.67% and 1.54%, respectively. CONCLUSION: aRO1mm lowers the radiation dose to OARs compared to the traditional approach, while maintaining adequate dose coverage on the target area. This method offers an improved strategy for managing uncertainties in radiation therapy planning for H&N cancer, enhancing treatment effectiveness.

The prognostic implications of radiologic extranodal extension in the lymph nodes of patients with nasopharyngeal cancer.

Objective: This study was developed to explore the prognostic relevance of radiologic extranodal extension (rENE) in lymph node-positive nasopharyngeal carcinoma (NPC) patients. Materials and methods: A retrospective review of data from 249 eligible patients with NPC was performed, with magnetic resonance imaging scans being used for rENE grading. The prognostic value of rENE was assessed through univariate and multivariate analyses. Results: Log-rank tests revealed significant differences between patients with and without rENE in terms of overall survival, progression-free survival (PFS) and distant metastasis-free survival (DMFS). G2 and G3 patients tended to exhibit worse PFS and DMFS relative to G0/G1 patients (p < 0.05). Long-term chemotherapy cycles were associated with significant improvements in the PFS and DMFS of G2 and G3 patients. Conclusion: These results suggest that higher rENE grades (G2/G3) are independently associated with worse survival outcomes among NPC patients, with more aggressive treatment strategies potentially affording greater prognostic benefits to these individuals.

[Box: see text].

Clinical significance of intensity-modulated radiotherapy (IMRT) to the distant metastatic lymph nodes for metastatic cervical cancer.

OBJECTIVE: To retrospectively explore the clinical significance of radiotherapy to the distant metastatic lymph nodes (cervical/ clavicular/ mediastinal et al.) in metastatic cervical cancer. Hereinto, these cervicothoracic lymph nodes were metastasized from IB1-IVA (initial stage at first treatment), and IVB initially had metastatic disease in these areas at diagnosis. METHODS: Metastatic cervical cancer only with the distant cervicothoracic metastatic lymph nodes (cervical/ clavicular/ mediastinal et al.), without distant parenchymal organs metastasis such as lung, liver, bone, and peritoneum, were enrolled in the analysis. These patients were classified into IB1-IVA and IVB based on their initial stage of first treatment. All patients received IMRT for the distant metastatic lymph nodes. The progression-free survival (PFS) and overall survival (OS) were analyzed using the Kaplan-Meier method. RESULTS: Overall, the median PFS was 9 months, and the median OS was 27 months. The subgroup analysis showed that for IB1-IVA, the median PFS was 11 months, and the median OS was 30.5 months. For IVB, the median PFS was 8 months, and the median OS was 16 months. CONCLUSION: Radiotherapy is beneficial to the distant metastatic lymph nodes (cervical/ clavicular/ mediastinal et al.), and could effectively bring the longer PFS and OS for metastatic cervical cancer.

Comparative effectiveness and cost-effectiveness of endoscopic nasopharyngectomy versus intensity-modulated radiotherapy in the treatment of recurrent nasopharyngeal carcinoma: A microsimulation analysis.

BACKGROUND: Nasopharyngeal carcinoma (NPC) is a significant health concern in southern China, like Guangdong and Hong Kong. This study aims to predict the effectiveness and cost-effectiveness of two prevalent NPC treatments, intensity-modulated radiotherapy (IMRT) and endoscopic nasopharyngectomy (ENPG). METHODS: A microsimulation model was developed to project the long-term outcomes of IMRT and ENPG, simulating 5000 patients with hypothetical locally recurrent NPC for each treatment option. The tumors of patients confined to the nasopharyngeal cavity, the post-naris or nasal septum, the superficial parapharyngeal space, or the base wall of the sphenoid sinus. Analyses were performed from the healthcare system perspectives of Mainland China and the healthcare provider perspective of Hong Kong, with input parameters sourced from the existing literature and databases. The robustness of findings was evaluated through one-way and probabilistic sensitivity analyses. RESULTS: For DFS, ENPG showed a 29% reduction in risk with an HR of 0.71 (95% CI: 0.64-0.77) compared to IMRT. ENPG demonstrated a significant survival benefit in OS with an HR of 0.59 (95% CI: 0.54-0.65), equating to a 41% reduction in mortality risk. In Hong Kong, IMRT and ENPG yielded QALY gains of 4.59 and 6.29, respectively, with ENPG exhibiting an incremental cost-effectiveness ratio (ICUR) of USD 13 057 per QALY. For Mainland China, ENPG denominated the IMRT and the ICUR was USD -1450 QALY. Probabilistic sensitivity analysis showed a 100% probability of ENPG being cost-effective at the willingness-to-pay thresholds of USD 130 490 per QALY in Hong Kong and USD 12 741 per QALY in Mainland China. CONCLUSION: The analysis confirms that ENPG is more effective and cost-effective than IMRT for treating recurrent NPC in both Hong Kong and Mainland China.

A Comprehensive Narrative Review of the Impact of Pelvic Radiotherapy on Pelvic Bone Health: Pathophysiology, Early Diagnosis, and Prevention Strategies.

Radiotherapy is a commonly used modality in pelvic malignancies such as prostate, gastrointestinal, or gynecological, either as a primary treatment or an adjuvant post-surgery. Despite its positive impact on the prognosis of these patients, it was found in several studies that it contributes to insufficiency fractures in different sites of the pelvis, more commonly in the sacral ala. This is particularly true for elderly patients. There are several hypotheses on how radiotherapy affects bone health, as it destroys the bone matrix and causes obliterative vasculitis. Several imaging techniques, particularly magnetic resonance imaging (MRI), help detect the radiotherapy-induced fracture and distinguish it from metastases. Some modalities, such as intensity-modulated radiotherapy (IMRT) and brachytherapy, have decreased fracture risk by escaping the adjacent structures to the targeted organ. Pharmacological interventions such as amifostine and desferrioxamine are promising in terms of bone protection, which necessitates further studies to confirm their mechanism of action.

Early recurrence as a pivotal event in nasopharyngeal carcinoma: identifying predictors and key molecular signals for survivors.

PURPOSE: The duration of response to treatment is a significant prognostic indicator, with early recurrence (ER) often predicting poorer survival outcomes in nasopharyngeal carcinoma (NPC) survivors. This study seeks to elucidate the factors contributing to the onset of ER following radiotherapy in NPC survivors. METHODS: This investigation encompassed 2,789 newly diagnosed NPC patients who underwent radical intensity-modulated radiotherapy. Ordinal logistic regression analysis was employed to evaluate the independent predictors of earlier recurrence. A machine learning-based prediction model of NPC recurrence patterns was developed. Tumorous RNA-sequencing (in-house cohort: N = 192) and biological tipping point analysis were utilized to infer potential molecular mechanisms associated with ER. RESULTS: Our results demonstrated that ER within 24 months post-initial treatment was the optimal time frame for identifying early malignant progression in NPC survivors. The ER cohort (150 of 2,789, 5.38%) exhibited a notably short median overall survival of 48.6 months. Multivariate analyses revealed that male gender, T4 stage, local or regional residual disease, detectable pre- and post-radiotherapy EBV DNA, and the absence of induction chemotherapy were significant predictors of earlier recurrence. The machine learning-based predictive model further underscored the importance of tumor-related factors in NPC recurrence. Moreover, ER emerged as a pivotal stage in NPC progression, with 15 critical transition signals identified potentially associated with the negative modulation of the immune response. CONCLUSIONS: Our comprehensive analysis of NPC recurrence patterns has unveiled insights into the key factors driving ER and provided novel insights into potential early warning biomarkers and the mechanisms underlying NPC progression.

Impact of Reference Selection on Gamma Analysis in Patient-Specific Quality Assurance for Monte Carlo-Based Treatment Planning Systems.

OBJECTIVE: Our study aimed to establish a standardized methodology for selecting "reference" and "evaluated" distributions in gamma analysis for Monte Carlo (MC) based intensity modulated treatment plans. Evaluation of importance of reference selection in MC based and non MC based treatment planning systems were analysed using a study classification. METHODS: Three categories were utilized to analyzed gamma passing rates across using different treatment planning systems (TPS) and detectors for thirty five patients. Category 1 utilized MC-based Monaco TPS plans and a 2 dimensional(2D) I'mRTMatriXX detector. Category 2 employed non-MC-based Eclipse TPS plans, assessed with a 2D I'mRTMatriXX detector. In Category 3, MC-based Monaco TPS plans were validated using a Dolphin detector. All plans were subjected to analysis using gamma criteria, which considered a dose difference of 3% and a distance to agreement of 3mm. Additionally, another set of gamma criteria was employed, with a dose difference of 3% and a distance to agreement of 2mm. An introduced Asymmetric factors in both 2D and 3D analysis will quantify the asymmetric nature of gamma based on the choice of "reference" distribution. RESULT: For 2D Gamma analysis, MC-based Monaco TPS and I'mRTMatriXX showed a consistent positive Zk2D trend for all patients, with significant p-values below 0.01 for both gamma passing criteria. In contrast, non-MC based Eclipse TPS exhibited varied Zk2D results, with non-significant p-values. In 3D Gamma analysis, all patients exhibited positive Zk3D values with significant p-values below 0.01 when "references" were swapped. The Pearson correlation between asymmetricity and isodose volumes was notably high at 0.99 for both gamma criteria. CONCLUSION: Our study highlights the imperative of using MC-based TPS as the definitive "reference" in gamma analysis for patient specific quality assurance of intensity modulated radiation therapy, emphasizing that variations can mislead results, especially given gamma analysis's sensitivity to MC calculation noise.

Dosimetric advantages of adaptive IMPT vs. Enhanced workload and treatment time - A need for automation.

INTRODUCTION: In head-and-neck IMPT, trigger-based offline plan adaptation (Offlinetrigger-based) is often used. Our goal was to compare this to four alternative adaptive strategies for dosimetry, workload and treatment time, considering also foreseen further technological advancements, including anticipated automation. MATERIALS AND METHODS: Alternative strategies included weekly offline re-planning (Offlineweekly), daily plan selection from a library (Librarystatic and Libraryprogsressive) and a fast, approximate daily online re-optimization approach (Onlinere-opt). Impact on CTV coverage and NTCPs was assessed by simulations based on repeat-CTs from 15 patients. Full daily re-planning was used as dosimetric benchmark. Increases in workload and treatment time were estimated. RESULTS: Both for coverage and NTCPs, fast Onlinere-opt performed as well as full re-planning. Compared to current practice, Onlinere-opt showed enhanced probabilities for high coverage, and resulted in reductions in grade ≥ II NTCPs of 4.6 ± 1.7 %-point for xerostomia and 4.2 ± 2.3 %-point for dysphagia. Offlineweekly and library strategies did not show coverage enhancements and resulted in smaller NTCP improvements. Further automation can largely limit workload and treatment time increases. With anticipated further automation, adaptation-related workload of Offlineweekly, Librarystatic, Libraryprogressive, and Onlinere-opt was expected to increase by 3, 8, 21, and 66 h for 35 fraction treatment courses compared to Offlinetrigger-based. The corresponding adaptation-related prolonged treatment times were estimated to be 0, 4, 6, and 29 min/fraction. CONCLUSION: Online adaptive strategies could approach dosimetric quality of full re-planning at the cost of additional workload and prolonged treatment time compared to the current offline adaptive strategy. Automation needs to play a key role in making more complex adaptive approaches feasible.

Monte Carlo dosimetry study of newly designed shielded applicators for intensity modulated brachytherapy of cervical and vaginal cancers.

INTRODUCTION: The utilization of metal shields in intensity-modulated brachytherapy (IMBT) enables the modulation of the dose, resulting in improved conformance to the tumor while simultaneously reducing the doses to organs at risk (OARs). Utilizing higher-energy sources like 60Co in IMBT for cervical and vaginal cancers has consistently posed challenges. This study evaluates the dosimetric aspects of modified applicators designed for IMBT using 60Co and 192Ir sources. MATERIALS AND METHODS: GATE, a Geant4-based simulation code, was utilized to model and simulate four distinct applicators. The clinical applicators were redesigned to place the structure of the source tube and the shield while keeping the general characteristics unchanged. These shields were evaluated by calculating transmission factors (TFs) and the dose homogeneities were also determined. RESULT: Transmission factors for the IMBT technique in redesigned intrauterine applicators and tungsten shields for iridium and cobalt sources were at least 12.8 and 65.4%, and these values were obtained for the intravaginal applicator at 0.2 and 7.0%, respectively. The dose homogeneities for all combinations of radionuclide-shield were within a 15% range of the non-IMBT applicators. CONCLUSION: This study has quantitatively evaluated the dosimetric effect of tungsten shields in the IMBT technique for cervical and vaginal cancer using cobalt sources. 192Ir compared to 60Co resulted in higher effectiveness for the designed intrauterine and intravaginal shields. while implementing tungsten shields in the redesigned applicators against the 60Co source may not offer complete protection, it does show promising results in reducing the dose to organs at risk.

Dose escalation in radical radio(chemo)therapy for cervical and upper thoracic esophageal cancer with 3DCRT/IMRT (ChC&UES): a multicenter retrospective study.

BACKGROUND: Cervical and upper thoracic esophageal cancer (ESCA) presents treatment challenges due to limited clinical evidence. This multi-center study (ChC&UES) explores radical radio(chemo)therapy efficacy and safety, especially focusing on radiation dose. METHOD: We retrospectively analyzed clinical data from 1,422 cases across 8 medical centers. According to the radiation dose for primary gross tumor, patients were divided into standard dose radiotherapy (SD, 50-55 Gy) or high dose (HD, > 55 Gy) radiotherapy. HD was further subdivided into conventional- high-dose group (HD-conventional, 55-63 Gy) and ultra-high-dose group (HD-ultra, ≥ 63 Gy). Primary outcome was Overall Survival (OS). RESULTS: The median OS was 33.0 months (95% CI: 29.401-36.521) in the whole cohort. Compared with SD, HD shown significant improved survival in cervical ESCA in Kaplan-Meier (P = 0.029) and cox multivariate regression analysis (P = 0.024) while shown comparable survival in upper thoracic ESCA (P = 0.735). No significant difference existed between HD-conventional and HD-ultra in cervical (P = 0.976) and upper thoracic (P = 0.610) ESCA. Incidences of radiation esophagitis and pneumonia from HD were comparable to SD (P = 0.097, 0.240), while myosuppression risk was higher(P = 0.039). The Bonferroni method revealed that, for both cervical and upper thoracic ESCA, HD-ultra enhance the objective response rate (ORR) compared to SD (P < 0.05). CONCLUSION: HD radiotherapy benefits cervical but not upper thoracic ESCA, while increasing bone marrow suppression risk. Further dose escalating (≥ 63 Gy) doesn't improve survival but enhances ORR.