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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.

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.

Introduction The magnitude and impact of rotational error is unclear in rectal cancer radiation therapy. This study evaluates rotational errors in rectal cancer patients, and investigates the feasibility of planning target volume (PTV) margin reduction to decrease organs at risk (OAR) irradiation. Methods In this study, 10 patients with rectal cancer were retrospectively selected. Rotational errors were assessed through image registration of daily cone beam computed tomography (CBCT) and planning CT scans. Two reference treatment plans (TPR) with PTV margins of 5 mm and 10 mm were generated for each patient. Pre‐determined rotational errors (±1°, ±3°, ±5°) were simulated to produce six manipulated treatment plans (TPM) from each TPR. Differences in evaluated dose‐volume metrics between TPR and TPM of each rotation were compared using Wilcoxon Signed‐Rank Test. Clinical compliance was investigated for statistically significant dose‐volume metrics. Results Mean rotational errors in pitch, roll and yaw were −0.72 ± 1.81°, −0.04 ± 1.36° and 0.38 ± 0.96° respectively. Pitch resulted in the largest potential circumferential displacement of clinical target volume (CTV) at 1.42 ± 1.06 mm. Pre‐determined rotational errors resulted in statistically significant differences in CTV, small bowel, femoral heads and iliac crests (P < 0.05). Only small bowel and iliac crests failed clinical compliance, with majority in the PTV 10 mm margin group. Conclusion Rotational errors affected clinical compliance for OAR dose but exerted minimal impact on CTV coverage even with reduced PTV margins. Both PTV margin reduction and rotational correction decreased irradiated volume of OAR. PTV margin reduction to 5 mm is feasible, and rotational corrections are recommended in rectal patients to further minimise OAR irradiation. To evaluate the magnitude and resulting impact of rotational error in rectal cancer patients, and to investigate the feasibility of planning target volume (PTV) margin reduction to improve organs‐at‐risk (OAR) sparing.

The aim of this study is to compare the effectiveness of carbon ion radiation therapy (CIRT), proton radiation therapy (PRT), and photon‐based intensity‐modulated radiation therapy (IMRT) in the treatment of sinonasal malignancies. We identified studies through systematic review and divided them into three cohorts (CIRT group/PRT group/IMRT group). Primary outcomes of interest were overall survival (OS) and local control (LC). We pooled the outcomes with meta‐analysis and compared the survival difference among groups using Chi2 (χ2) test. A representative sample of 2282 patients with sinonasal malignancies (911 in the CIRT group, 599 in the PRT group, and 772 in the IMRT group) from 44 observation studies (7 CIRT, 16 PRT, and 21 IMRT) was included. The pooled 3‐year OS, LC, distant metastasis–free survival, and progression‐free survival rates were 67.0%, 72.8%, 69.4%, and 52.8%, respectively. Through cross‐group analysis, the OS was significantly higher after CIRT (75.1%, 95% CI: 67.1%‐83.2%) than PRT (66.2%, 95% CI: 57.7%‐74.6%; χ2 = 13.374, P < .0001) or IMRT (63.8%, 95% CI: 55.3%‐72.3%; χ2 = 23.814, P < .0001). LC was significantly higher after CIRT (80.2%, 95% CI: 73.9%‐86.5%) than PRT (72.9%, 95% CI: 63.7%‐82.0%; χ2 = 8.955, P = .003) or IMRT (67.8%, 95% CI: 59.4%‐76.2%; χ2 = 30.955, P < .0001). However, no significant difference between PRT and IMRT for OS and LC was observed. CIRT appeared to provide better OS and LC for patients with malignancies of nasal cavity and paranasal sinuses. A prospective randomized clinical trial is needed to confirm the superiority of CIRT in the treatment of sinonasal tumors. Carbon‐ion radiation therapy achieved higher overall survival and local control rates as compared to both proton radiation therapy and photon based intensity‐modulated radiation therapy through meta‐analysis of 2, 282 patients with sinonasal malignancies from the real world. CIRT appeared to provide better OS and LC for patients with malignancies of nasal cavity and paranasal sinuses.

Standard doses of conventionally fractionated radiation have had minimal to no impact on the survival duration of patients with locally advanced unresectable pancreatic cancer (LAPC). The use of low-dose stereotactic body radiation (SBRT) in 3- to 5-fractionshas thus far produced a modest improvement in median survival with minimal toxicity and shorter duration of treatment, but failed to produce a meaningful difference at 2 years and beyond. A much higher biologically effective dose (BED) is likely needed to achieve tumor ablation The challenge is the delivery of ablative doses near the very sensitive gastrointestinal tract. Advanced organ motion management, image guidance, and adaptive planning techniques enable delivery of ablative doses of radiation (> = 100Gy BED) when more protracted hypofractionated regimens or advanced image guidance and adaptive planning are used. This approach has resulted in encouraging improvements in survival in several studies. This review will summarize the evolution of the radiation technique over time from conventional to ablative and describe the practical aspects of delivering ablative doses near the GI tract using cone beam CT image (CBCT) guidance and online adaptive MRI guidance.

This book covers the fundamental knowledge required to implement the IGRT techniques in abdominal cancer treatment with detailed operational procedures involved, and also provides an overview of emerging techniques for future application. This is an ideal text for Radiation oncologists, medical physicists, dosimetrists, and radiation therapists.

Hypofractionated radiotherapy for prostate cancer has gained increased attention due to its proposed high radiation-fraction sensitivity. Recent reports from studies comparing moderately hypofractionated and conventionally fractionated radiotherapy support the clinical use of moderate hypofractionation. To date, there are no published randomised studies on ultra-hypofractionated radiotherapy. Here, we report the outcomes of the Scandinavian HYPO-RT-PC phase 3 trial with the aim to show non-inferiority of ultra-hypofractionation compared with conventional fractionation. In this open-label, randomised, phase 3 non-inferiority trial done in 12 centres in Sweden and Denmark, we recruited men up to 75 years of age with intermediate-to-high-risk prostate cancer and a WHO performance status between 0 and 2. Patients were randomly assigned to ultra-hypofractionation (42·7 Gy in seven fractions, 3 days per week for 2·5 weeks) or conventional fractionated radiotherapy (78·0 Gy in 39 fractions, 5 days per week for 8 weeks). No androgen deprivation therapy was allowed. The primary endpoint was time to biochemical or clinical failure, analysed in the per-protocol population. The prespecified non-inferiority margin was 4% at 5 years, corresponding to a critical hazard ratio (HR) limit of 1·338. Physician-recorded toxicity was measured according to the Radiation Therapy Oncology Group (RTOG) morbidity scale and patient-reported outcome measurements with the Prostate Cancer Symptom Scale (PCSS) questionnaire. This trial is registered with the ISRCTN registry, number ISRCTN45905321. Between July 1, 2005, and Nov 4, 2015, 1200 patients were randomly assigned to conventional fractionation (n=602) or ultra-hypofractionation (n=598), of whom 1180 (591 conventional fractionation and 589 ultra-hypofractionation) constituted the per-protocol population. 1054 (89%) participants were intermediate risk and 126 (11%) were high risk. Median follow-up time was 5·0 years (IQR 3·1–7·0). The estimated failure-free survival at 5 years was 84% (95% CI 80–87) in both treatment groups, with an adjusted HR of 1·002 (95% CI 0·758–1·325; log-rank p=0·99). There was weak evidence of an increased frequency of acute physician-reported RTOG grade 2 or worse urinary toxicity in the ultra-hypofractionation group at end of radiotherapy (158 [28%] of 569 patients vs 132 [23%] of 578 patients; p=0·057). There were no significant differences in grade 2 or worse urinary or bowel late toxicity between the two treatment groups at any point after radiotherapy, except for an increase in urinary toxicity in the ultra-hypofractionation group compared to the conventional fractionation group at 1-year follow-up (32 [6%] of 528 patients vs 13 [2%] of 529 patients; (p=0·0037). We observed no differences between groups in frequencies at 5 years of RTOG grade 2 or worse urinary toxicity (11 [5%] of 243 patients for the ultra-hypofractionation group vs 12 [5%] of 249 for the conventional fractionation group; p=1·00) and bowel toxicity (three [1%] of 244 patients vs nine [4%] of 249 patients; p=0·14). Patient-reported outcomes revealed significantly higher levels of acute urinary and bowel symptoms in the ultra-hypofractionation group compared with the conventional fractionation group but no significant increases in late symptoms were found, except for increased urinary symptoms at 1-year follow-up, consistent with the physician-evaluated toxicity. Ultra-hypofractionated radiotherapy is non-inferior to conventionally fractionated radiotherapy for intermediate-to-high risk prostate cancer regarding failure-free survival. Early side-effects are more pronounced with ultra-hypofractionation compared with conventional fractionation whereas late toxicity is similar in both treatment groups. The results support the use of ultra-hypofractionation for radiotherapy of prostate cancer. The Nordic Cancer Union, the Swedish Cancer Society, and the Swedish Research Council.

The complexity of head and neck cancers (HNC) mandates a multidisciplinary approach and radiation therapy (RT) plays a critical role in the optimal management of patients with HNC, either as frontline or adjuvant treatment postoperatively. The advent of both definitive and post-operative RT has significantly improved the outcomes of patients with HNC. Herein, we discuss the role of postoperative RT in different subtypes of HNC, its side effects, and the importance of surveillance. The treatment regions discussed in this paper are the oral cavity, nasopharynx, paranasal sinus cavity, oropharynx, larynx and hypopharynx. Multiple studies that demonstrate the importance of definitive and/or postoperative RT, which led to an improved outlook of survival for HNC patients will be discussed.

Spatially fractionated radiotherapy has been shown to have effects on the immune system that differ from conventional radiotherapy (CRT). We compared several aspects of the immune response to CRT relative to a model of spatially fractionated radiotherapy (RT), termed microplanar radiotherapy (MRT). MRT delivers hundreds of grays of radiation in submillimeter beams (peak), separated by non-radiated volumes (valley). We have developed a preclinical method to apply MRT by a commercial small animal irradiator. Using a B16-F10 murine melanoma model, we first evaluated the in vitro and in vivo effect of MRT, which demonstrated significant treatment superiority relative to CRT. Interestingly, we observed insignificant treatment responses when MRT was applied to Rag−/− and CD8-depleted mice. An immuno-histological analysis showed that MRT recruited cytotoxic lymphocytes (CD8), while suppressing the number of regulatory T cells (Tregs). Using RT-qPCR, we observed that, compared to CRT, MRT, up to the dose that we applied, significantly increased and did not saturate CXCL9 expression, a cytokine that plays a crucial role in the attraction of activated T cells. Finally, MRT combined with anti-CTLA-4 ablated the tumor in half of the cases, and induced prolonged systemic antitumor immunity.

Magnetic resonance imaging (MRI) provides excellent visualization of central nervous system (CNS) tumors due to its superior soft tissue contrast. Magnetic resonance-guided radiotherapy (MRgRT) has historically been limited to use in the initial treatment planning stage due to cost and feasibility. MRI-guided linear accelerators (MRLs) allow clinicians to visualize tumors and organs at risk (OARs) directly before and during treatment, a process known as online MRgRT. This novel system permits adaptive treatment planning based on anatomical changes to ensure accurate dose delivery to the tumor while minimizing unnecessary toxicity to healthy tissue. These advancements are critical to treatment adaptation in the brain and spinal cord, where both preliminary MRI and daily CT guidance have typically had limited benefit. In this narrative review, we investigate the application of online MRgRT in the treatment of various CNS malignancies and any relevant ongoing clinical trials. Imaging of glioblastoma patients has shown significant changes in the gross tumor volume over a standard course of chemoradiotherapy. The use of adaptive online MRgRT in these patients demonstrated reduced target volumes with cavity shrinkage and a resulting reduction in radiation dose to uninvolved tissue. Dosimetric feasibility studies have shown MRL-guided stereotactic radiotherapy (SRT) for intracranial and spine tumors to have potential dosimetric advantages and reduced morbidity compared with conventional linear accelerators. Similarly, dosimetric feasibility studies have shown promise in hippocampal avoidance whole brain radiotherapy (HA-WBRT). Next, we explore the potential of MRL-based multiparametric MRI (mpMRI) and genomically informed radiotherapy to treat CNS disease with cutting-edge precision. Lastly, we explore the challenges of treating CNS malignancies and special limitations MRL systems face.