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This textbook covers a basis of mathematical algorithm in artificial intelligence and clinical adaptation and contribution of AI in radiotherapy. More experienced practitioners and researchers and members of medical physics communities, such as AAPM, ASTRO, and ESTRO, would find this book extremely useful.

Background In locoregionally advanced nasopharyngeal carcinoma (LANPC) patients, variance of tumor response to induction chemotherapy (ICT) was observed. We developed and validated a novel imaging biomarker to predict which patients will benefit most from additional ICT compared with chemoradiotherapy (CCRT) alone. Methods All patients, including retrospective training ( n  = 254) and prospective randomized controlled validation cohorts (a substudy of NCT01245959, n  = 248), received ICT+CCRT or CCRT alone. Primary endpoint was failure-free survival (FFS). From the multi-parameter magnetic resonance images of the primary tumor at baseline, 819 quantitative 2D imaging features were extracted. Selected key features (according to their interaction effect between the two treatments) were combined into an Induction Chemotherapy Outcome Score (ICTOS) with a multivariable Cox proportional hazards model using modified covariate method. Kaplan-Meier curves and significance test for treatment interaction were used to evaluate ICTOS, in both cohorts. Results Three imaging features were selected and combined into ICTOS to predict treatment outcome for additional ICT. In the matched training cohort, patients with a high ICTOS had higher 3-year and 5-year FFS in ICT+CCRT than CCRT subgroup (69.3% vs. 45.6% for 3-year FFS, and 64.0% vs. 36.5% for 5-year FFS; HR = 0.43, 95% CI = 0.25–0.74, p  = 0.002), whereas patients with a low ICTOS had no significant difference in FFS between the subgroups ( p  = 0.063), with a significant treatment interaction ( p interaction  <  0.001). This trend was also found in the validation cohort with high ( n  = 73, ICT+CCRT 89.7% and 89.7% vs. CCRT 61.8% and 52.8% at 3-year and 5-year; HR = 0.17, 95% CI = 0.06–0.51, p  <  0.001) and low ICTOS ( n  = 175, p  = 0.31), with a significant treatment interaction ( p interaction  = 0.019). Compared with 12.5% and 16.6% absolute benefit in the validation cohort (3-year FFS from 69.9 to 82.4% and 5-year FFS from 63.4 to 80.0% from additional ICT), high ICTOS group in this cohort had 27.9% and 36.9% absolute benefit. Furthermore, no significant survival improvement was found from additional ICT in both groups after stratifying low ICTOS patients into low-risk and high-risks groups, by clinical risk factors. Conclusion An imaging biomarker, ICTOS, as proposed, identified patients who were more likely to gain additional survival benefit from ICT+CCRT (high ICTOS), which could influence clinical decisions, such as the indication for ICT treatment. Trial registration ClinicalTrials.gov , NCT01245959 . Registered 23 November 2010.

Radiation therapy (RT) continues to play an important role in the treatment of cancer. Adaptive RT (ART) is a novel method through which RT treatments are evolving. With the ART approach, computed tomography or magnetic resonance (MR) images are obtained as part of the treatment delivery process. This enables the adaptation of the irradiated volume to account for changes in organ and/or tumor position, movement, size, or shape that may occur over the course of treatment. The advantages and challenges of ART maybe somewhat abstract to oncologists and clinicians outside of the specialty of radiation oncology. ART is positioned to affect many different types of cancer. There is a wide spectrum of hypothesized benefits, from small toxicity improvements to meaningful gains in overall survival. The use and application of this novel technology should be understood by the oncologic community at large, such that it can be appropriately contextualized within the landscape of cancer therapies. Likewise, the need to test these advances is pressing. MR-guided ART (MRgART) is an emerging, extended modality of ART that expands upon and further advances the capabilities of ART. MRgART presents unique opportunities to iteratively improve adaptive image guidance. However, although the MRgART adaptive process advances ART to previously unattained levels, it can be more expensive, time-consuming, and complex. In this review, the authors present an overview for clinicians describing the process of ART and specifically MRgART.

Background A dummy run was conducted to ensure the quality of intensity-modulated radiotherapy (IMRT) before registration in a randomized phase III study of elderly patients with newly diagnosed glioblastoma by the Japan Clinical Oncology Group 1910 (JCOG1910). Methods All 41 institutions enrolled in this study were required to report outlining that included gross tumor volume (GTV), clinical target volume (CTV), planning target volume (PTV), and treatment planning for one benchmark case. First, deviations in outlining were evaluated using the Dice similarity coefficient (DSC) and mean distance agreement (MDA), compared to reference targets delineated by the research secretariat. Second, the participating institutions were required to create treatment plans for arms A (40.05 Gy in 15 fractions) and B (25 Gy in 5 fractions) using IMRT techniques. The quality of the outlining and dose-volume criteria for each target and organs at risk were evaluated. Results Six institutions failed to adhere to the protocol and required revision due to insufficient GTV outlining, not considering anatomical barriers for CTV, and modifying PTV against protocols. Compared to the reference outlining, the means and standard deviations of DSC and MDA were 0.37 ± 0.19 and 9.41 ± 3.99 mm for GTV; 0.80 ± 0.08 and 4.31 ± 1.85 mm for CTV; and 0.83 ± 0.05 and 4.23 ± 1.45 mm for PTV, respectively. Regarding dose-volume criteria, 40 of the 41 institutions met the per-protocol limits; only one was within the acceptable limits. Conclusions Several institutions demonstrated deviations in outlining that necessitated revisions. Thus, appropriate feedback and periodic sharing of information with participating institutions is necessary in the upcoming prospective JCOG1910 study.

Purpose Results of a prospective, randomized controlled trial at our institute demonstrate an association between the dose to the left hippocampus and neurocognitive decline post‐radiotherapy for patients with glioblastoma. To minimize the dose to the left hippocampus, a left hippocampus sparing model was created using RapidPlan (RP) and multi‐criteria optimization (MCO). Materials and methods For 147 patients with newly diagnosed glioblastoma treated with volumetric modulated arc therapy (VMAT), the left and right hippocampus were delineated. Ninety‐seven of 147 VMAT plans were used to configure a RP model named HCS1. The remaining 50 VMAT plans were used for the model validation. All 97 plans were replanned with the HCS1 and further optimized using MCO (HCS1+MCO). MCO was used to explore the trade‐off between reducing the left hippocampus mean dose and planning objectives for the targets and other organs‐at‐risk (OAR) for HCS1 plans. These plans were used to create a new model called HCS2. MCO and RP model configuration were done within the Eclipse treatment planning system. Results The final HCS2 model decreased the mean dose to the left hippocampus by 26% compared to clinically treated plans without reducing target coverage for 50 validation data. The mean dose to the left hippocampus decreased from 32.65 Gy in clinically treated plans, 30.45 Gy in HCS1‐generated plans, and 24.04 Gy in HCS2‐generated plans. The mean volume receiving 95% of the prescription dose (V95%) of the planning target volume was 99.08% ± 1.39% in clinically treated plans, 99.03% ± 1.37% in HCS1‐generated plans, and 98.80% ± 1.48% in HCS2‐generated plans. Mean dose to 0.1 cc of the brainstem improved from 45.91 Gy in clinically treated plans to 39.29 Gy in HCS2‐generated plans. Conclusions The RP model and MCO helps to decrease left hippocampus mean dose while maintaining the target volume coverage and OAR sparing comparable to clinically treated plans for glioblastoma patients.

Background Bone metastases in the lower spine and pelvis are effectively palliated with radiotherapy (RT), though this can come with side effects such as radiation induced nausea and vomiting (RINV). We hypothesize that high rates of RINV occur in part because of the widespread use of inexpensive simple unplanned palliative radiotherapy (SUPR), over more complex and resource intensive 3D conformal RT, such as volumetric modulated arc therapy (VMAT). Methods This is a randomized, multi-centre phase III trial of SUPR versus VMAT. We will accrue 250 patients to assess the difference in patient-reported RINV. This study is powered to detect a difference in quality of life between patients treated with VMAT vs. SUPR. Discussion This trial will determine if VMAT reduces early toxicity compared to SUPR and may provide justification for this more resource-intensive and costly form of RT. Trial registration Clinicaltrials.gov identifier: NCT03694015 . Date of registration: October 3, 2018.

The book provides a review of concepts and methodologies developed and adopted for quantitative imaging-guided radiation dosimetry calculations in targeted radionuclide. It also provides an overview of model design of anthropomorphic computational models and software packages developed for Monte Carlo-based dosimetry calculations.

To investigate the clinical efficacy and treatment toxicity of volume-modulated arc therapy (VMAT) for nasopharyngeal carcinoma (NPC). 205 VMAT-treated NPC patients from our cancer center were prospectively entrolled. All patients received 68-70 Gy irradiation based on the planning target volume of the primary gross tumor volume. Acute and late toxicities were graded according to the Common Terminology Criteria for Adverse Events v3.0 and Radiation Therapy Oncology Group Late Radiation Morbidity Scoring Criteria. The median follow-up period was 37.3 months (range, 6.3-45.1 months). The 3-year estimated local failure-free survival, regional failure-free survival, locoregional failure-free survival, distant metastasis-free survival, disease-free survival and overall survival were 95.5%, 97.0%, 94.0%, 92.1%, 86.8% and 97.0%, respectively. Cox regression analysis showed primary gross tumor volume, N stage and EBV-DNA to be independent predictors of VMAT outcomes (P < 0.05). The most common acute and late side effects were grade 2-3 mucositis (78%) and xerostomia (83%, 61%, 34%, and 9% at 3, 6, 12 and 24 months after VMAT), respectively. VMAT for the primary treatment of NPC achieved very high locoregional control with a favorable toxicity profile. The time-saving benefit of VMAT will enable more patients to receive precision radiotherapy.

Background Conservative surgery followed by breast and nodal irradiation is the standard loco-regional early breast cancer (BC) treatment for patients with four or more involved lymph nodes. However, the treatment strategy when fewer nodes are involved remains unclear, especially when lymphadenectomy has not been performed. Sensitive nodal status assessment molecular techniques as the One-Step Nucleic Acid Amplification (OSNA) assay can contribute to the definition and standardization of the treatment strategy. Therefore, the OPTIMAL study aims to demonstrate the feasibility of incidental irradiation of axillary nodes in patients with early-stage BC and limited involvement of the SLN. Methods BC patients who underwent conservative surgery and whose SLN total tumour load assessed with OSNA ranged between 250–15,000 copies/µL will be eligible. Patients will be randomized to receive irradiation on the breast, tumour bed, axillary and supraclavicular lymph node areas (intentional arm) or only on the breast and tumour bed (incidental arm). All areas, including the internal mammary chain, will be contoured. The mean, median, D5% and D95% doses received in all volumes will be calculated. The primary endpoint is the non-inferiority of the incidental irradiation of axillary nodes compared to the intentional irradiation in terms of 5-year disease free survival. Secondary endpoints comprise the comparison of acute and chronic toxicity and loco-regional and distant disease recurrence rates. Discussion Standardizing the treatment and diagnosis of BC patients with few nodes affected is crucial due to the lack of consensus. Hence, the quantitative score for the metastatic burden of SLN provided by OSNA can contribute by improving the discrimination of which BC patients with limited nodal involvement can benefit from incidental radiation as an adjuvant treatment strategy. Trial registration ClinicalTrial.gov, NCT02335957; https://clinicaltrials.gov/ct2/show/NCT02335957

ABSTRACT This study evaluates current practices and challenges associated with computed tomography number-to-mass density (CT–MD) conversion tables in helical tomotherapy across Japan and explores directions for standardization and quality improvement amid the increasing adoption of adaptive radiotherapy (ART). A nationwide web-based survey was conducted across 34 institutions utilizing the Radixact system. Data were collected on CT acquisition protocols, calibration phantoms, density plugs, reconstruction algorithms, table registration timing and quality assurance (QA) frequency. Registered CT–MD tables were categorized by CT modality: Simulation CT (SimCT), ClearRT and CTrue. ClearRT tables were analyzed by phantom setup (full vs half), and CTrue tables by reconstruction method [filtered back projection (FPB) vs iterative reconstruction (IR)]. Inter-institutional variations in CT numbers and the number of data points were assessed. SimCT tables exhibited the widest variation in the number of data points (median = 10) and high-density CT numbers. ClearRT tables (median = 8) showed variations of up to 300 Hounsfield units (HU) in cortical bone; the half-phantom setup reduced inter-institutional variability. CTrue tables (median = 8) demonstrated high consistency, with negligible differences between IR and FPB. All plug CT numbers of CTrue remained within the tolerance defined by the American Association of Physicists in Medicine Task Group 148. However, CT numbers for air plugs varied by ~±30 HU, indicating inconsistent handling of air reference values. Additionally, 43% of institutions did not perform routine QA. Standardizing phantom geometry, air CT number handling and QA protocols—particularly using half-phantom calibration—may improve CT–MD table consistency and dose accuracy in ART.