Functional brain imaging interventions for radiation therapy planning in patients with glioblastoma: a systematic review.

RATIONALE: This systematic review aims to synthesise the outcomes of different strategies of incorporating functional biological markers in the radiation therapy plans of patients with glioblastoma to support clinicians and further research. METHODS: The systematic review protocol was registered on PROSPERO (CRD42021221021). A structured search for publications was performed following PRISMA guidelines. Quality assessment was performed using the Newcastle-Ottawa Scale. Study characteristics, intervention methodology and outcomes were extracted using Covidence. Data analysis focused on radiation therapy target volumes, toxicity, dose distributions, recurrence and survival mapped to functional image-guided radiotherapy interventions. RESULTS: There were 5733 citations screened, with 53 citations (n = 32 studies) meeting review criteria. Studies compared standard radiation therapy planning volumes with functional image-derived volumes (n = 20 studies), treated radiation therapy volumes with recurrences (n = 15 studies), the impact on current standard target delineations (n = 9 studies), treated functional volumes and survival (n = 8 studies), functionally guided dose escalation (n = 8 studies), radiomics (n = 4 studies) and optimal organ at risk sparing (n = 3 studies). The approaches to target outlining and dose escalation were heterogeneous. The analysis indicated an improvement in median overall survival of over two months compared with a historical control group. Simultaneous-integrated-boost dose escalation of 72-76 Gy in 30 fractions appeared to have an acceptable toxicity profile when delivered with inverse planning to a volume smaller than 100 cm[Formula: see text]. CONCLUSION: There was significant heterogeneity between the approaches taken by different study groups when implementing functional image-guided radiotherapy. It is recommended that functional imaging data be incorporated into the gross tumour volume with appropriate technology-specific margins used to create the clinical target volume when designing radiation therapy plans for patients with glioblastoma.

The dosimetric advantages of perirectal hydrogel spacer in men with localized prostate cancer undergoing stereotactic ablative radiotherapy (SABR).

To evaluate the dosimetric differences for patients receiving a perirectal hydrogel spacer (PR-HS) using SpaceOAR undergoing stereotactic ablative radiotherapy (SABR) for localized prostate cancer with the CyberKnife VSI system. Gold fiducial markers and a PR-HS was inserted in 22 consecutive patients with histologically confirmed localized prostate cancer. For planning comparison, dosimetry from the clinical plans was compared against replans based on a simulated rectum volume designed to recreate a clinically appropriate spacer-less anatomy for each patient. Both sets were planned to 36.25 Gy in 5 fractions using the treatment planning system associated with the CyberKnife VSI system. The aim was to ensure equivalent target coverage for both plans and to evaluate doses to the organs-at-risk (OARs): rectum, bladder and penile bulb. The median PR-HS implant volume was 11.2 cc (range 8.8 to 14.9 cc). The maximal median perirectal separation was 15.5 mm (10.5 to 20.7 mm). Statistically significant reductions were noted for the 3 OARs, with no statistically significant difference in planning target volumes or clinical target volume coverage. All rectal dose constraints were significantly improved in the PR-HS plans with a percentage dose difference of at least 24% (rectum V18.1Gy (%)) to 60.5% (rectum V36Gy (cc)). The bladder and penile bulb dose constraints parameters were also significantly improved: the bladder V37Gy was reduced by 17.1%, V18.1Gy was reduced by 4.2%; the penile bulb D50% was reduced by 7.7%. The use of PR-HS was able to significantly reduce planned dose to the rectum, bladder and penile bulb with SABR techniques associated with the CyberKnife VSI system.

Improvement in bladder volume reproducibility using A-mode portable ultrasound bladder scanner in moderate-hypofractionated volumetric modulated arc therapy for prostate cancer patients.

PURPOSE: This study introduced an A-mode portable ultrasound bladder scanner, the Lilium® α-200 (here after Lilium; Lilium Otsuka, Kanagawa, Japan), for the treatment of prostate cancer patients with hypofractionated volumetric modulated arc therapy to improve the reproducibility of bladder volume (BV). MATERIALS AND METHODS: Thirty patients were advised to maintain full BV prior to computed tomography (CT) simulation and daily treatment. Among these, the BV of 15 patients was measured using Lilium until a BV of 80% in the simulation was achieved (with the Lilium group). Daily cone-beam CT (CBCT) was performed for treatment. The correlation between BV measured by CBCT and Lilium was assessed. The differences in the BV and dosimetric parameters of the bladder in the CBCT versus planning CT were compared between the groups with and without Lilium. RESULTS: There was a significantly strong relationship (r = 0.796, p < 0.05) between the BVs measured using CBCT and Lilium. The relative BV ratios to simulation CT < 0.5 and > 2 were observed in 10.3% and 12.7%, respectively, of treatment sessions without Lilium group, while these ratios were 1% and 2.8%, respectively, in the Lilium group. The mean absolute difference in the range of V30Gy to V40Gy without Lilium sessions was significantly larger (p < 0.05) than that in the Lilium group. CONCLUSION: The use of the A-mode portable ultrasound bladder scanner significantly improved the reproducibility of the BV, resulting in few variations in the dosimetric parameters for the bladder.

Performance of a knowledge-based planning model for optimizing intensity-modulated radiotherapy plans for partial breast irradiation.

PURPOSE: To evaluate a knowledge-based (KB) planning model for RapidPlan, generated using a five-field intensity-modulated radiotherapy (IMRT) class solution beam strategy and rigorous dosimetric constraints for accelerated partial breast irradiation (APBI). MATERIALS AND METHODS: The RapidPlan model was configured using 64 APBI treatment plans and validated for 120 APBI patients who were not included in the training dataset. KB plan dosimetry was compared to clinical plan dosimetry, the clinical planning constraints, and the constraints used in phase III APBI trials. Dosimetric differences between clinical and KB plans were evaluated using paired two-tailed Wilcoxon signed-rank tests. RESULTS: KB planning was able to produce IMRT-based APBI plans in a single optimization without manual intervention that are comparable or better than the conventionally optimized, clinical plans. Comparing KB plans to clinical plans, differences in PTV, heart, contralateral breast, and ipsilateral lung dose-volume metrics were not clinically significant. The ipsilateral breast volume receiving at least 50% of the prescription dose was statistically and clinically significantly lower in the KB plans. CONCLUSION: KB planning for IMRT-based APBI provides equivalent or better dosimetry compared to conventional inverse planning. This model may be reliably applied in clinical practice and could be used to transfer planning expertise to ensure consistency in APBI plan quality.

Estimating cancer risks due to whole lungs low dose radiotherapy with different techniques for treating COVID-19 pneumonia.

BACKGROUND: Low dose radiotherapy (LDRT) of whole lungs with photon beams is a novel method for treating COVID-19 pneumonia. This study aimed to estimate cancer risks induced by lung LDRT for different radiotherapy delivery techniques. METHOD: Four different radiotherapy techniques, including 3D-conformal with anterior and posterior fields (3D-CRT AP-PA), 3D-conformal with 8 coplanar fields (3D-CRT 8 fields), eight fields intensity-modulated radiotherapy (IMRT), and volumetric modulated arc therapy using 2 full arcs (VMAT) were planned on the CT images of 32 COVID-19 patients with the prescribed dose of 1 Gy to the lungs. Organ average and maximum doses, and PTV dose distribution indexes were compared between different techniques. The radiation-induced cancer incidence and cancer-specific mortality, and cardiac heart disease risks were estimated for the assessed techniques. RESULTS: In IMRT and VMAT techniques, heart (mean and max), breast (mean, and max), and stomach (mean) doses and also maximum dose in the body were significantly lower than the 3D-CRT techniques. The calculated conformity indexes were similar in all the techniques. However, the homogeneity indexes were lower (i.e., better) in intensity-modulated techniques (P < 0.03) with no significant differences between IMRT and VMAT plans. Lung cancer incident risks for all the delivery techniques were similar (P > 0.4). Cancer incidence and mortality risks for organs located closer to lungs like breast and stomach were higher in 3D-CRT techniques than IMRT or VMAT techniques (excess solid tumor cancer incidence risks for a 30 years man: 1.94 ± 0.22% Vs. 1.68 ± 0.17%; and women: 6.66 ± 0.81% Vs. 4.60 ± 0.43%: cancer mortality risks for 30 years men: 1.63 ± 0.19% Vs. 1.45 ± 0.15%; and women: 3.63 ± 0.44% Vs. 2.94 ± 0.23%). CONCLUSION: All the radiotherapy techniques had low cancer risks. However, the overall estimated risks induced by IMRT and VMAT radiotherapy techniques were lower than the 3D-CRT techniques and can be used clinically in younger patients or patients having greater concerns about radiation induced cancers.

COVID-19 and radiotherapy: potential new strategies for patients management with hypofractionation and telemedicine.

COVID-19 disease is one of the biggest public health challenges in Italy and global healthcare facilities, including radiotherapy departments, faced an unprecedented emergency. Cancer patients are at higher risk of COVID-19 infection because of their immunosuppressive state caused by both tumor itself and anticancer therapy adopted. In this setting, the radiation therapy clinical decision-making process has been partly reconsidered; thus, to reduce treatment duration and minimize infection risk during a pandemic, hypofractionated regimens have been revised. Moreover, telemedicine shows its helpfulness in the radiotherapy field, and patients get the supportive care they need minimizing their access to hospitals. This review aims to point out the importance of hypofractionated RT and telemedicine in cancer patient management in the COVID-19 era.

Effect of Surgical Mask on Setup Error in Head and Neck Radiotherapy.

PURPOSE: With the widespread prevalence of Corona Virus Disease 2019 (COVID-19), cancer patients are suggested to wear a surgical mask during radiation treatment. In this study, cone beam CT (CBCT) was used to investigate the effect of surgical mask on setup errors in head and neck radiotherapy. METHODS: A total of 91 patients with head and neck tumors were selected. CBCT was performed to localize target volume after patient set up. The images obtained by CBCT before treatment were automatically registered with CT images and manually fine-tuned. The setup errors of patients in 6 directions of Vrt, Lng, Lat, Pitch, Roll and Rotation were recorded. The patients were divided into groups according to whether they wore the surgical mask, the type of immobilization mask used and the location of the isocenter. The setup errors of patients were calculated. A t-test was performed to detect whether it was statistically significant. RESULTS: In the 4 groups, the standard deviation in the directions of Lng and Pitch of the with surgical mask group were all higher than that in the without surgical mask group. In the head-neck-shoulder mask group, the mean in the Lng direction of the with surgical mask group was larger than that of the without surgical mask group. In the lateral isocenter group, the mean in the Lng and Pitch directions of the with surgical mask group were larger than that of the without surgical mask group. The t-test results showed that there was significant difference in the setup error between the 2 groups (p = 0.043 and p = 0.013, respectively) only in the Lng and Pitch directions of the head-neck-shoulder mask group. In addition, the setup error of 6 patients with immobilization open masks exhibited no distinguished difference from that of the patients with regular immobilization masks. CONCLUSION: In the head and neck radiotherapy patients, the setup error was affected by wearing surgical mask. It is recommended that the immobilization open mask should be used when the patient cannot finish the whole treatment with a surgical mask.

Use of Receiver Operating Curve Analysis and Machine Learning With an Independent Dose Calculation System Reduces the Number of Physical Dose Measurements Required for Patient-Specific Quality Assurance.

PURPOSE: Our purpose was to assess the use of machine learning methods and Mobius 3D (M3D) dose calculation software to reduce the number of physical ion chamber (IC) dose measurements required for patient-specific quality assurance during corona virus disease 2019. METHODS AND MATERIALS: In this study, 1464 inversely planned treatments using Pinnacle or Raystation treatment planning software (TPS) were delivered using Elekta Versa HD and Varian Truebeam and Truebeam STx linear accelerators between June 2018 and November 2019. For each plan, an independent dose calculation was performed using M3D, and an absolute dose measurement was taken using a Pinpoint IC inside the Mobius phantom. The point dose differences between the TPS and M3D calculation and between TPS and IC measurements were calculated. Agreement between the TPS and IC was used to define the ground truth plan failure. To reduce the on-site personnel during the pandemic, 2 methods of receiver operating characteristic analysis (n = 1464) and machine learning (n = 603) were used to identify patient plans that would require physical dose measurements. RESULTS: In the receiver operating characteristic analysis, a predelivery M3D difference threshold of 3% identified plans that failed an IC measurement at a 4% threshold with 100% sensitivity and 76.3% specificity. This indicates that fewer than 25% of plans required a physical dose measurement. A threshold of 1% on a machine learning model was able to identify plans that failed an IC measurement at a 3% threshold with 100% sensitivity and 54.3% specificity, leading to fewer than 50% of plans that required a physical dose measurement. CONCLUSIONS: It is possible to identify plans that are more likely to fail IC patient-specific quality assurance measurements before delivery. This possibly allows for a reduction of physical measurements taken, freeing up significant clinical resources and reducing the required amount of on-site personnel while maintaining patient safety.

Non-operative management for oral cavity carcinoma: Definitive radiation therapy as a potential alternative treatment approach.

PURPOSE: To determine the outcomes of oral cavity squamous cell cancer (OSCC) patients treated with non-surgical approach i.e. definitive intensity-modulated radiation therapy (IMRT). METHODS: All OSCC patients treated radically with IMRT (without primary surgery) between 2005-2014 were reviewed in a prospectively collected database. OSCC patients treated with definitive RT received concurrent chemotherapy except for early stage patients or those who declined or were unfit for chemotherapy. The 5-year local, and regional, distant control rates, disease-free, overall, and cancer-specific survival, and late toxicity were analyzed. RESULTS: Among 1316 OSCC patients treated with curative-intent; 108 patients (8%) received non-operative management due to: medical inoperability (n = 14, 13%), surgical unresectability (n = 8, 7%), patient declined surgery (n = 15, 14%), attempted preservation of oral structure/function in view of required extensive surgery (n = 53, 49%) or extensive oropharyngeal involvement (n = 18, 17%). Sixty-eight (63%) were cT3-4, 38 (35%) were cN2-3, and 38 (35%) received concurrent chemotherapy. With a median follow-up of 52 months, the 5-year local, regional, distant control rate, disease-free, overall, and cancer-specific survival were 78%, 92%, 90%, 42%, 50%, and 76% respectively. Patients with cN2-3 had higher rate of 5-year distant metastasis (24% vs 3%, p = 0.001), with detrimental impact on DFS (p = 0.03) and OS (p < 0.02) on multivariable analysis. Grade ≥ 3 late toxicity was reported in 9% of patients (most common: grade 3 osteoradionecrosis in 6%). CONCLUSIONS: Non-operative management of OSCC resulted in a meaningful rate of locoregional control, and could be an alternative curative approach when primary surgery would be declined, unsuitable or unacceptably delayed.

A plan template-based automation solution using a commercial treatment planning system.

PURPOSE: The purpose of this study was to develop an auto-planning platform to be interfaced with a commercial treatment planning system (TPS). The main goal was to obtain robust and high-quality plans for different anatomic sites and various dosimetric requirements. METHODS: Monaco (Elekta, St. Louis, US) was the TPS in this work. All input parameters for inverse planning could be defined in a plan template inside Monaco. A software tool called Robot Framework was used to launch auto-planning trials with updated plan templates. The template modifier external to Monaco was the major component of our auto-planning platform. For current implementation, it was a rule-based system that mimics the trial-and-error process of an experienced planner. A template was automatically updated by changing the optimization constraints based on dosimetric evaluation of the plan obtained in the previous trial, along with the data of the iterative optimization extracted from Monaco. Treatment plans generated by Monaco with all plan evaluation criteria satisfied were considered acceptable, and such plans would be saved for further evaluation by clinicians. The auto-planning platform was validated for 10 prostate and 10 head-and-neck cases in comparison with clinical plans generated by experienced planners. RESULTS: The performance and robustness of our auto-planning platform was tested with clinical cases of prostate and head and neck treatment. For prostate cases, automatically generated plans had very similar plan quality with the clinical plans, and the bladder volume receiving 62.5 Gy, 50 Gy, and 40 Gy in auto-plans was reduced by 1%, 3%, and 5%, respectively. For head and neck cases, auto-plans had better conformity with reduced dose to the normal structures but slightly higher dose inhomogeneity in the target volume. Remarkably, the maximum dose in the spinal cord and brain stem was reduced by more than 3.5 Gy in auto-plans. Fluence map optimization only with less than 30 trials was adequate to generate acceptable plans, and subsequent optimization for final plans was completed by Monaco without further intervention. The plan quality was weakly dependent on the parameter selection in the initial template and the choices of the step sizes for changing the constraint values. CONCLUSION: An automated planning platform to interface with Monaco was developed, and our reported tests showed preliminary results for prostate and head and neck cases.

Head and neck cancer radiotherapy amid COVID-19 pandemic: Report from Milan, Italy.

BACKGROUND: Management of head and neck cancers (HNC) in radiation oncology in the coronavirus disease 2019 (COVID-19) era is challenging. Aim of our work is to report organization strategies at a radiation therapy (RT) department in the first European area experiencing the COVID-19 pandemic. METHODS: We focused on (a) dedicated procedures for HNC, (b) RT scheduling, and (c) health care professionals' protection applied during the COVID-19 breakdown (from March 1, 2020 to April 30, 2020). RESULTS: Applied procedures are reported and discussed. Forty-three patients were treated. Image-guided, intensity modulated RT was performed in all cases. Median overall treatment time was 50 (interquartile range: 47-54.25) days. RT was interrupted/delayed in seven patients (16%) for suspected COVID-19 infection. Two health professionals managing HNC patients were proven as COVID-19 positive. CONCLUSION: Adequate and well-timed organization allowed for the optimization of HNC patients balancing at the best of our possibilities patients' care and personnel's safety.

Hypofractionated radiotherapy alone with 2.4 Gy per fraction for head and neck cancer during the COVID-19 pandemic: The Princess Margaret experience and proposal.

BACKGROUND: The objective of this study was to identify a subgroup of patients with head and neck squamous cell carcinoma (HNSCC) who might be suitable for hypofractionated radiotherapy (RT-hypo) during the COVID-19 pandemic. METHODS: HNSCC cases (oropharynx/larynx/hypopharynx) treated with definitive RT-hypo (60 Gy in 25 fractions over 5 weeks), moderately accelerated radiotherapy (RT-acc) alone (70 Gy in 35 fractions over 6 weeks), or concurrent chemoradiotherapy (CCRT) during 2005-2017 were included. Locoregional control (LRC) and distant control (DC) after RT-hypo, RT-acc, and CCRT were compared for various subgroups. RESULTS: The study identified 994 human papillomavirus-positive (HPV+) oropharyngeal squamous cell carcinoma cases (with 61, 254, and 679 receiving RT-hypo, RT-acc, and CCRT, respectively) and 1045 HPV- HNSCC cases (with 263, 451, and 331 receiving RT-hypo, RT-acc, and CCRT, respectively). The CCRT cohort had higher T/N categories, whereas the radiotherapy-alone patients were older. The median follow-up was 4.6 years. RT-hypo, RT-acc, and CCRT produced comparable 3-year LRC and DC for HPV+ T1-2N0-N2a disease (seventh edition of the TNM system [TNM-7]; LRC, 94%, 100%, and 94%; P = .769; DC, 94%, 100%, and 94%; P = .272), T1-T2N2b disease (LRC, 90%, 94%, and 97%; P = .445; DC, 100%, 96%, and 95%; P = .697), and T1-2N2c/T3N0-N2c disease (LRC, 89%, 93%, and 95%; P = .494; DC, 89%, 90%, and 87%; P = .838). Although LRC was also similar for T4/N3 disease (78%, 84%, and 88%; P = .677), DC was significantly lower with RT-hypo or RT-acc versus CCRT (67%, 65%, and 87%; P = .005). For HPV- HNSCC, 3-year LRC and DC were similar with RT-hypo, RT-acc, and CCRT in stages I and II (LRC, 85%, 89%, and 100%; P = .320; DC, 99%, 98%, and 100%; P = .446); however, RT-hypo and RT-acc had significantly lower LRC in stage III (76%, 69%, and 91%; P = .006), whereas DC rates were similar (92%, 85%, and 90%; P = .410). Lower LRC in stage III predominated in patients with laryngeal squamous cell carcinoma receiving RT-acc (62%) but not RT-hypo (80%) or CCRT (92%; RT-hypo vs CCRT: P = .270; RT-acc vs CCRT: P = .004). CCRT had numerically higher LRC in comparison with RT-hypo or RT-acc in stage IV (73%, 65%, and 66%; P = .336). CONCLUSIONS: It is proposed that RT-hypo be considered in place of CCRT for HPV+ T1-T3N0-N2c (TNM-7) HNSCCs, HPV- T1-T2N0 HNSCCs, and select stage III HNSCCs during the COVID-19 outbreak.