Deep learning-based optimization of field geometry for total marrow irradiation delivered with volumetric modulated arc therapy.

BACKGROUND: Total marrow (lymphoid) irradiation (TMI/TMLI) is a radiotherapy treatment used to selectively target the bone marrow and lymph nodes in conditioning regimens for allogeneic hematopoietic stem cell transplantation. A complex field geometry is needed to cover the large planning target volume (PTV) of TMI/TMLI with volumetric modulated arc therapy (VMAT). Five isocenters and ten overlapping fields are needed for the upper body, while, for patients with large anatomical conformation, two specific isocenters are placed on the arms. The creation of a field geometry is clinically challenging and is performed by a medical physicist (MP) specialized in TMI/TMLI. PURPOSE: To develop convolutional neural networks (CNNs) for automatically generating the field geometry of TMI/TMLI. METHODS: The dataset comprised 117 patients treated with TMI/TMLI between 2011 and 2023 at our Institute. The CNN input image consisted of three channels, obtained by projecting along the sagittal plane: (1) average CT pixel intensity within the PTV; (2) PTV mask; (3) brain, lungs, liver, bowel, and bladder masks. This "averaged" frontal view combined the information analyzed by the MP when setting the field geometry in the treatment planning system (TPS). Two CNNs were trained to predict the isocenters coordinates and jaws apertures for patients with (CNN-1) and without (CNN-2) isocenters on the arms. Local optimization methods were used to refine the models output based on the anatomy of the patient. Model evaluation was performed on a test set of 15 patients in two ways: (1) by computing the root mean squared error (RMSE) between the CNN output and ground truth; (2) with a qualitative assessment of manual and generated field geometries-scale: 1 = not adequate, 4 = adequate-carried out in blind mode by three MPs with different expertise in TMI/TMLI. The Wilcoxon signed-rank test was used to evaluate the independence of the given scores between manual and generated configurations (p < 0.05 significant). RESULTS: The average and standard deviation values of RMSE for CNN-1 and CNN-2 before/after local optimization were 15 ± 2/13 ± 3 mm and 16 ± 2/18 ± 4 mm, respectively. The CNNs were integrated into a planning automation software for TMI/TMLI such that the MPs could analyze in detail the proposed field geometries directly in the TPS. The selection of the CNN model to create the field geometry was based on the PTV width to approximate the decision process of an experienced MP and provide a single option of field configuration. We found no significant differences between the manual and generated field geometries for any MP, with median values of 4 versus 4 (p = 0.92), 3 versus 3 (p = 0.78), 4 versus 3 (p = 0.48), respectively. Starting from October 2023, the generated field geometry has been introduced in our clinical practice for prospective patients. CONCLUSIONS: The generated field geometries were clinically acceptable and adequate, even for an MP with high level of expertise in TMI/TMLI. Incorporating the knowledge of the MPs into the development cycle was crucial for optimizing the models, especially in this scenario with limited data.

Deep learning and atlas-based models to streamline the segmentation workflow of total marrow and lymphoid irradiation.

PURPOSE: To improve the workflow of total marrow and lymphoid irradiation (TMLI) by enhancing the delineation of organs at risk (OARs) and clinical target volume (CTV) using deep learning (DL) and atlas-based (AB) segmentation models. MATERIALS AND METHODS: Ninety-five TMLI plans optimized in our institute were analyzed. Two commercial DL software were tested for segmenting 18 OARs. An AB model for lymph node CTV (CTV_LN) delineation was built using 20 TMLI patients. The AB model was evaluated on 20 independent patients, and a semiautomatic approach was tested by correcting the automatic contours. The generated OARs and CTV_LN contours were compared to manual contours in terms of topological agreement, dose statistics, and time workload. A clinical decision tree was developed to define a specific contouring strategy for each OAR. RESULTS: The two DL models achieved a median [interquartile range] dice similarity coefficient (DSC) of 0.84 [0.71;0.93] and 0.85 [0.70;0.93] across the OARs. The absolute median Dmean difference between manual and the two DL models was 2.0 [0.7;6.6]% and 2.4 [0.9;7.1]%. The AB model achieved a median DSC of 0.70 [0.66;0.74] for CTV_LN delineation, increasing to 0.94 [0.94;0.95] after manual revision, with minimal Dmean differences. Since September 2022, our institution has implemented DL and AB models for all TMLI patients, reducing from 5 to 2 h the time required to complete the entire segmentation process. CONCLUSION: DL models can streamline the TMLI contouring process of OARs. Manual revision is still necessary for lymph node delineation using AB models.

Repeat Gamma Knife radiosurgery for recurrent trigeminal neuralgia in patients with multiple sclerosis: a single-center retrospective study.

PURPOSE: Gamma Knife radiosurgery (GKRS) has emerged as an effective treatment option for trigeminal neuralgia (TN) in patients with multiple sclerosis (MS). To date, the outcomes of repeat GKRS for patients with TN and MS with recurrent pain have been investigated in a few patients. This study aims to report the outcomes and predictive factors of pain reduction for MS patients undergoing repeat GKRS for recurrent TN. METHODS: Eighteen patients with MS underwent repeat GKRS for recurrent TN. A retrospective chart review and telephone interviews were conducted to determine background medical history, dosimetric data, and outcomes of the procedure. Facial pain and sensory function were evaluated using the Barrow Neurological Institute (BNI) scales. RESULTS: Fifteen patients achieved a BNI pain score of IIIa or better, indicating pain reduction, within a median period of 21 days after repeat GKRS. The maximum dose for repeat GKRS ranged from 70 to 85 Gy. Pain recurred in 5 patients after a median period of 12 months after GKRS. Percentages of patients with pain reduction at 1, 2, 3, 5, and 7 years were 60%, 60%, 50%, 50%, and 50%, respectively. Older age at repeat GKRS predicted sustained pain reduction (P = 0.01). Seven patients developed facial sensory disturbances, which were bothersome in two patients. CONCLUSIONS: Repeat GKRS may be used as an effective treatment modality for prolonging the duration of pain reduction time in patients with MS and TN. After repeat GKRS, facial sensory disturbances are common; however, they are often not bothersome.

Twenty Years of Advancements in a Radiotherapy Facility: Clinical Protocols, Technology, and Management.

BACKGROUND: Hypo-fractionation can be an effective strategy to lower costs and save time, increasing patient access to advanced radiation therapy. To demonstrate this potential in practice within the context of temporal evolution, a twenty-year analysis of a representative radiation therapy facility from 2003 to 2022 was conducted. This analysis utilized comprehensive data to quantitatively evaluate the connections between advanced clinical protocols and technological improvements. The findings provide valuable insights to the management team, helping them ensure the delivery of high-quality treatments in a sustainable manner. METHODS: Several parameters related to treatment technique, patient positioning, dose prescription, fractionation, equipment technology content, machine workload and throughput, therapy times and patients access counts were extracted from departmental database and analyzed on a yearly basis by means of linear regression. RESULTS: Patients increased by 121 ± 6 new per year (NPY). Since 2010, the incidence of hypo-fractionation protocols grew thanks to increasing Linac technology. In seven years, both the average number of fractions and daily machine workload decreased by -0.84 ± 0.12 fractions/year and -1.61 ± 0.35 patients/year, respectively. The implementation of advanced dose delivery techniques, image guidance and high dose rate beams for high fraction doses, currently systematically used, has increased the complexity and reduced daily treatment throughput since 2010 from 40 to 32 patients per 8 h work shift (WS8). Thanks to hypo-fractionation, such an efficiency drop did not affect NPY, estimating 693 ± 28 NPY/WS8, regardless of the evaluation time. Each newly installed machine was shown to add 540 NPY, while absorbing 0.78 ± 0.04 WS8. The COVID-19 pandemic brought an overall reduction of 3.7% of patients and a reduction of 0.8 fractions/patient, to mitigate patient crowding in the department. CONCLUSIONS: The evolution of therapy protocols towards hypo-fractionation was supported by the use of proper technology. The characteristics of this process were quantified considering time progression and organizational aspects. This strategy optimized resources while enabling broader access to advanced radiation therapy. To truly value the benefit of hypo-fractionation, a reimbursement policy should focus on the patient rather than individual treatment fractionation.

Can STEreotactic Body Radiation Therapy (SBRT) Improve the Prognosis of Unresectable Locally Advanced Pancreatic Cancer? Long-Term Clinical Outcomes, Toxicity and Prognostic Factors on 142 Patients (STEP Study).

AIM: The gold standard of care for pancreatic adenocarcinoma is the integrated treatment of surgery and chemotherapy (ChT), but about 50% of patients present with unresectable disease. Our study evaluated the efficacy in terms of local control, survival and safety of stereotactic body radiation therapy (SBRT) in locally advanced pancreatic cancer (LAPC). METHODS: A retrospective study (STEP study) analyzed patients with LAPC treated with a dose of 45 Gy in 6 fractions. Local control (LC), distant progression free survival (DPFS), overall survival (OS) and toxicity were analyzed according to the Kaplan-Meier method. RESULTS: A total of 142 patients were evaluated. Seventy-six patients (53.5%) received induction ChT before SBRT. The median follow-up was 11 months. One-, 2- and 3-year LC rate was 81.9%, 69.1% and 58.5%. Median DPFS was 6.03 months; 1- and 2-year DPFS rate was 19.9% and 4.5%. Median OS was 11.6 months and 1-, 2- and 3-year OS rates were 45.4%, 16.1%, and 9.8%. At univariate analysis, performed by the log-rank test, age < 70 years (p = 0.037), pre-SBRT ChT (p = 0.004) and post-SBRT ChT (p = 0.019) were associated with better OS. No patients experienced G3 toxicity. CONCLUSION: SBRT represents an effective and safe therapeutic option in the multimodal treatment of patients with LAPC in terms of increased LC. When SBRT was sequentially integrated with ChT, the treatment proved to be promising in terms of OS as well.

Total tumor volume as a predictor of survival in patients with multiple oligometastases treated with stereotactic ablative radiotherapy (SABR).

BACKGROUND: Delivering stereotactic ablative radiotherapy (SABR) in patients with multiple oligometastases represents a challenge for clinical and technical reasons. We aimed to evaluate the outcome of patients affected by multiple oligometastases treated with SABR and the impact of tumor volume on survival. MATERIALS AND METHODS: We included all the patients treated with single course SABR for 3 to 5 extracranial oligometastases. All patients were treated with the volumetric modulated arc therapy (VMAT) technique with ablative intent. End-points of the analysis were overall survival (OS), progression free survival (PFS), local control (LC) and toxicity. RESULTS: 136 patients were treated from 2012 to 2020 on 451 oligometastases. Most common primary tumor was colorectal cancer (44.1%) followed by lung cancer (11.8%). A total of 3, 4 and 5 lesions were simultaneously treated in 102 (75.0%), 26 (19.1%), and 8 (5.9%) patients, respectively. Median total tumor volume (TTV) was 19.1 cc (range 0.6-245.1). With a median follow-up of 25.0 months, OS at 1 and 3 years was 88.4% and 50.2%, respectively. Increasing TTV was independent predictive factor of worse OS (HR 2.37, 95% CI 1.18-4.78, p = 0.014) and PFS (HR 1.63, 95% CI 1.05-2.54; p = 0.028). Median OS was 80.6 months if tumor volume was ≤ 10 cc (1 and 3 years OS rate 93.6% and 77.5%, respectively), and 31.1 months if TTV was higher than 10 cc (1 and 3 years OS rate 86.7% and 42.3%, respectively). Rates of LC at 1 and 3 years were 89.3% and 76.5%. In terms of toxicity, no grade 3 or higher toxicity was reported both in the acute and late settings. CONCLUSION: We demonstrated the impact of tumor volume on survival and disease control of patients affected by multiple oligometastases treated with single course SABR.

Enhancing Radiotherapy Workflow for Head and Neck Cancer with Artificial Intelligence: A Systematic Review.

BACKGROUND: Head and neck cancer (HNC) is characterized by complex-shaped tumors and numerous organs at risk (OARs), inducing challenging radiotherapy (RT) planning, optimization, and delivery. In this review, we provided a thorough description of the applications of artificial intelligence (AI) tools in the HNC RT process. METHODS: The PubMed database was queried, and a total of 168 articles (2016-2022) were screened by a group of experts in radiation oncology. The group selected 62 articles, which were subdivided into three categories, representing the whole RT workflow: (i) target and OAR contouring, (ii) planning, and (iii) delivery. RESULTS: The majority of the selected studies focused on the OARs segmentation process. Overall, the performance of AI models was evaluated using standard metrics, while limited research was found on how the introduction of AI could impact clinical outcomes. Additionally, papers usually lacked information about the confidence level associated with the predictions made by the AI models. CONCLUSIONS: AI represents a promising tool to automate the RT workflow for the complex field of HNC treatment. To ensure that the development of AI technologies in RT is effectively aligned with clinical needs, we suggest conducting future studies within interdisciplinary groups, including clinicians and computer scientists.

Impact of the Extremities Positioning on the Set-Up Reproducibility for the Total Marrow Irradiation Treatment.

Total marrow (lymph node) irradiation (TMI/TMLI) delivery requires more time than standard radiotherapy treatments. The patient's extremities, through the joints, can experience large movements. The reproducibility of TMI/TMLI patients' extremities was evaluated to find the best positioning and reduce unwanted movements. Eighty TMI/TMLI patients were selected (2013-2022). During treatment, a cone-beam computed tomography (CBCT) was performed for each isocenter to reposition the patient. CBCT-CT pairs were evaluated considering: (i) online vector shift (OVS) that matched the two series; (ii) residual vector shift (RVS) to reposition the patient's extremities; (iii) qualitative agreement (range 1-5). Patients were subdivided into (i) arms either leaning on the frame or above the body; (ii) with or without a personal cushion for foot positioning. The Mann-Whitney test was considered (p < 0.05 significant). Six-hundred-twenty-nine CBCTs were analyzed. The median OVS was 4.0 mm, with only 1.6% of cases ranked < 3, and 24% of RVS > 10 mm. Arms leaning on the frame had significantly smaller RVS than above the body (median: 8.0 mm/6.0 mm, p < 0.05). Using a personal cushion for the feet significantly improved the RVS than without cushions (median: 8.5 mm/1.8 mm, p < 0.01). The role and experience of the radiotherapy team are fundamental to optimizing the TMI/TMLI patient setup.

Multicentric evaluation of a machine learning model to streamline the radiotherapy patient specific quality assurance process.

PURPOSE: Patient-specific quality assurance (PSQA) is performed to ensure that modulated treatment plans can be delivered as intended, but constitutes a substantial workload that could slow down the radiotherapy process and delay the start of clinical treatments. In this study, we investigated a machine learning (ML) tree-based ensemble model to predict the gamma passing rate (GPR) for volumetric modulated arc therapy (VMAT) plans. MATERIALS AND METHODS: 5622 VMAT plans from multiple treatment sites were selected from a database of Institution 1 and the ML model trained using 19 metrics. PSQA analyses were performed automatically using criteria 3%/1 mm (global normalization, absolute dose, 10% threshold) and 95% action limit. Model's performance was evaluated on an out-of-sample test set of Institution 1 and on two independent sets of measurements collected at Institution 2 and Institution 3. Mean absolute error (MAE), as well as the model's sensitivity and specificity, were computed. RESULTS: The model obtained a MAE of 2.33%, 2.54% and 3.91% for the three Institutions, with a specificity of 0.90, 0.90 and 0.68, and a sensitivity of 0.61, 0.25, and 0.55, respectively. Small positive median values of the residuals (i.e., the difference between measurements and predictions) were observed for each Institution (0.95%, 1.66%, and 3.42%). Thus, the model's predictions were, on average, close to the real values and provided a conservative estimation of the GPR. CONCLUSIONS: ML models can be integrated into clinical practice to streamline the radiotherapy workflow, but they should be center-specific or thoroughly verified within centers before clinical use.

Evaluation of plan complexity and dosimetric plan quality of total marrow and lymphoid irradiation using volumetric modulated arc therapy.

PURPOSE: To assess the impact of the planner's experience and optimization algorithm on the plan quality and complexity of total marrow and lymphoid irradiation (TMLI) delivered by means of volumetric modulated arc therapy (VMAT) over 2010-2022 at our institute. METHODS: Eighty-two consecutive TMLI plans were considered. Three complexity indices were computed to characterize the plans in terms of leaf gap size, irregularity of beam apertures, and modulation complexity. Dosimetric points of the target volume (D2%) and organs at risk (OAR) (Dmean) were automatically extracted to combine them with plan complexity and obtain a global quality score (GQS). The analysis was stratified based on the different optimization algorithms used over the years, including a knowledge-based (KB) model. Patient-specific quality assurance (QA) using Portal Dosimetry was performed retrospectively, and the gamma agreement index (GAI) was investigated in conjunction with plan complexity. RESULTS: Plan complexity significantly reduced over the years (r = -0.50, p < 0.01). Significant differences in plan complexity and plan dosimetric quality among the different algorithms were observed. Moreover, the KB model allowed to achieve significantly better dosimetric results to the OARs. The plan quality remained similar or even improved during the years and when moving to a newer algorithm, with GQS increasing from 0.019 ± 0.002 to 0.025 ± 0.003 (p < 0.01). The significant correlation between GQS and time (r = 0.33, p = 0.01) indicated that the planner's experience was relevant to improve the plan quality of TMLI plans. Significant correlations between the GAI and the complexity metrics (r = -0.71, p < 0.01) were also found. CONCLUSION: Both the planner's experience and algorithm version are crucial to achieve an optimal plan quality in TMLI plans. Thus, the impact of the optimization algorithm should be carefully evaluated when a new algorithm is introduced and in system upgrades. Knowledge-based strategies can be useful to increase standardization and improve plan quality of TMLI treatments.

Adaptive Volumetric-Modulated Arc Radiation Therapy for Head and Neck Cancer: Evaluation of Benefit on Target Coverage and Sparing of Organs at Risk.

BACKGROUND: Radiotherapy is essential in the management of head-neck cancer. During the course of radiotherapy, patients may develop significant anatomical changes. Re-planning with adaptive radiotherapy may ensure adequate dose coverage and sparing of organs at risk. We investigated the consequences of adaptive radiotherapy on head-neck cancer patients treated with volumetric-modulated arc radiation therapy compared to simulated non-adaptive plans: Materials and methods: We included in this retrospective dosimetric analysis 56 patients treated with adaptive radiotherapy. The primary aim of the study was to analyze the dosimetric differences with and without an adaptive approach for targets and organs at risk, particularly the spinal cord, parotid glands, oral cavity and larynx. The original plan (OPLAN) was compared to the adaptive plan (APLAN) and to a simulated non-adaptive dosimetric plan (DPLAN). RESULTS: The non-adaptive DPLAN, when compared to OPLAN, showed an increased dose to all organs at risk. Spinal cord D2 increased from 27.91 (21.06-31.76) Gy to 31.39 (27.66-38.79) Gy (p = 0.00). V15, V30 and V45 of the DPLAN vs. the OPLAN increased by 20.6% (p = 0.00), 14.78% (p = 0.00) and 15.55% (p = 0.00) for right parotid; and 16.25% (p = 0.00), 18.7% (p = 0.00) and 20.19% (p = 0.00) for left parotid. A difference of 36.95% was observed in the oral cavity V40 (p = 0.00). Dose coverage was significantly reduced for both CTV (97.90% vs. 99.96%; p = 0.00) and PTV (94.70% vs. 98.72%; p = 0.00). The APLAN compared to the OPLAN had similar values for all organs at risk. CONCLUSIONS: The adaptive strategy with re-planning is able to avoid an increase in dose to organs at risk and better target coverage in head-neck cancer patients, with potential benefits in terms of side effects and disease control.

Internal Guidelines for Reducing Lymph Node Contour Variability in Total Marrow and Lymph Node Irradiation.

BACKGROUND: The total marrow and lymph node irradiation (TMLI) target includes the bones, spleen, and lymph node chains, with the latter being the most challenging structures to contour. We evaluated the impact of introducing internal contour guidelines to reduce the inter- and intraobserver lymph node delineation variability in TMLI treatments. METHODS: A total of 10 patients were randomly selected from our database of 104 TMLI patients so as to evaluate the guidelines' efficacy. The lymph node clinical target volume (CTV_LN) was recontoured according to the guidelines (CTV_LN_GL_RO1) and compared to the historical guidelines (CTV_LN_Old). Both topological (i.e., Dice similarity coefficient (DSC)) and dosimetric (i.e., V95 (the volume receiving 95% of the prescription dose) metrics were calculated for all paired contours. RESULTS: The mean DSCs were 0.82 ± 0.09, 0.97 ± 0.01, and 0.98 ± 0.02, respectively, for CTV_LN_Old vs. CTV_LN_GL_RO1, and between the inter- and intraobserver contours following the guidelines. Correspondingly, the mean CTV_LN-V95 dose differences were 4.8 ± 4.7%, 0.03 ± 0.5%, and 0.1 ± 0.1%. CONCLUSIONS: The guidelines reduced the CTV_LN contour variability. The high target coverage agreement revealed that historical CTV-to-planning-target-volume margins were safe, even if a relatively low DSC was observed.

Radiosurgery of limited brain metastases from primary solid tumor: results of the randomized phase III trial (NCT02355613) comparing treatments executed with a specialized or a C-arm linac-based platform.

BACKGROUND: Comparative prospective data regarding different radiosurgery (SRS) modalities for treating brain metastases (BMs) from solid tumors are not available. To investigate with a single institute phase III randomized trial whether SRS executed with linac (Arm-B) is superior to a dedicated multi-source gamma-ray stereotactic platform (Arm-A). METHODS: Adults patients with 1-4 BMs from solid tumors up to 30 mm in maximum diameter were randomly assigned to arms A and B. The primary endpoint was cumulative incidence of symptomatic (grade 2-3) radionecrosis (CIRN). Secondary endpoints were local progression cumulative incidence (CILP), distant brain failure, disease-free survival (DFS), and overall survival (OS). RESULTS: A total of 251 patients were randomly assigned to Arm-A (121) or Arm-B (130). The 1-year RN cumulative incidence was 6.7% in whole cohort, 3.8% (95% CI 1.9-7.4%) in Arm-B, and 9.3% (95% CI 6.2-13.8%) in the Arm-A (p = 0.43). CIRN was influenced by target volume irradiated only for the Arm-A (p << 0.001; HR 1.36 [95% CI 1.25-1.48]). Symptomatic RN occurred in 56 cases at a median time of 10.3 months (range 1.15-54.8 months), 27 in the Arm-B at a median time of 15.9 months (range 4.9-54.8 months), and 29 in the Arm-A at a median time of 6.9 months (1.2-32.3 months), without statistically significant differences between the two arms. No statistically significant differences were recorded between the two arms in CILP, BDF, DFS or OS. The mean beam-on time to deliver SRS was 49.0 ± 36.2 min in Arm-A, and 3.1 ± 1.6 min in Arm-B. CONCLUSIONS: Given the technical differences between the treatment platforms investigated in this single-institution study, linac-based SRS (Arm-B) did not lead to significantly lower grade 2-3 RN rates versus the multi-source gamma-ray system (Arm-A) in a population of patients with limited brain metastases of small volume. No significant difference in local control was observed between both arms. For Arm-B, the treatment delivery time was significantly lower than for Arm-A. TRIAL REGISTRATION: ClinicalTrials.gov Identifier NCT02355613.

Predictive value of clinical and radiomic features for radiation therapy response in patients with lymph node-positive head and neck cancer.

BACKGROUND: Prediction of survival and radiation therapy response is challenging in head and neck cancer with metastatic lymph nodes (LNs). Here we developed novel radiomics- and clinical-based predictive models. METHODS: Volumes of interest of LNs were employed for radiomic features extraction. Radiomic and clinical features were investigated for their predictive value relatively to locoregional failure (LRF), progression-free survival (PFS), and overall survival (OS) and used to build multivariate models. RESULTS: Hundred and six subjects were suitable for final analysis. Univariate analysis identified two radiomic features significantly predictive for LRF, and five radiomic features plus two clinical features significantly predictive for both PFS and OS. The area under the curve of receiver operating characteristic curve combining clinical and radiomic predictors for PFS and OS resulted 0.71 (95%CI: 0.60-0.83) and 0.77 (95%CI: 0.64-0.89). CONCLUSIONS: Radiomic and clinical features resulted to be independent predictive factors, but external independent validation is mandatory to support these findings.

The impact of stereotactic ablative radiotherapy on oligoprogressive metastases from renal cell carcinoma.

BACKGROUND: Renal cell carcinoma (RCC) represents 80-90% of all kidney tumors and about 15-25% of patients will develop distant metastases. Systemic therapy represents the standard of care for metastatic patients, but stereotactic ablative radiotherapy (SABR) may play a relevant role in the oligoprogressive setting, defined as the progression of few metastases during an ongoing systemic therapy on a background of otherwise stable disease. Aim of the present study was to analyze the outcome of RCC patients treated with SABR on oligoprogressive metastases. MATERIALS AND METHODS: In this monocenter study, we analyzed patients affected by RCC treated with SABR on a maximum of 5 cranial or extracranial oligoprogressive sites of disease. Endpoints were overall survival (OS), progression-free survival (PFS), and toxicity. RESULTS: We included 74 oligoprogressions (26 intracranial and 48 extracranial) and 57 SABR treatments in 44 patients. Most common concomitant treatments were sunitinib (28, 49.1%), pazopanib (12, 21.0%) and nivolumab (11, 19.3%). Median follow-up was 19.0 months, and 1- and 2-year OS rates were 79.2% and 57.3%, respectively. Repeated SABR was a positive predictive factor for OS (p = 0.034). Median PFS was 9.8 months, with 1- and 2-year rates of 43.2% and 25.8%. At multivariable analysis, disease-free interval (p = 0.022) and number of treated metastases (p = 0.007) were significant for PFS. About 80% of patients continued the ongoing systemic therapy 1- and 2-years after SABR with no grade 3 or 4 toxicities. CONCLUSIONS: we confirmed the efficacy and safety of SABR for oligoprogression from RCC, with the potential to ablate resistant metastases and to prolong the ongoing systemic therapy.

Automatic planning of the lower extremities for total marrow irradiation using volumetric modulated arc therapy.

PURPOSE: Total marrow (and lymphoid) irradiation (TMI-TMLI) is limited by the couch travel range of modern linacs, which forces the treatment delivery to be split into two plans with opposite orientations: a head-first supine upper-body plan, and a feet-first supine lower extremities plan. A specific field junction is thus needed to obtain adequate target coverage in the overlap region of the two plans. In this study, an automatic procedure was developed for field junction creation and lower extremities plan optimization. METHODS: Ten patients treated with TMI-TMLI at our institution were selected retrospectively. The planning of the lower extremities was performed automatically. Target volume parameters (CTV_J­V98% > 98%) at the junction region and several dose statistics (D98%, Dmean, and D2%) were compared between automatic and manual plans. The modulation complexity score (MCS) was used to assess plan complexity. RESULTS: The automatic procedure required 60-90 min, depending on the case. All automatic plans achieved clinically acceptable dosimetric results (CTV_J­V98% > 98%), with significant differences found at the junction region, where Dmean and D2% increased on average by 2.4% (p < 0.03) and 3.0% (p < 0.02), respectively. Similar plan complexity was observed (median MCS = 0.12). Since March 2022, the automatic procedure has been introduced in our clinic, reducing the TMI-TMLI simulation-to-delivery schedule by 2 days. CONCLUSION: The developed procedure allowed treatment planning of TMI-TMLI to be streamlined, increasing efficiency and standardization, preventing human errors, while maintaining the dosimetric plan quality and complexity of manual plans. Automated strategies can simplify the future adoption and clinical implementation of TMI-TMLI treatments in new centers.

Acute Toxicity and Quality of Life in a Post-Prostatectomy Ablative Radiation Therapy (POPART) Multicentric Trial.

BACKGROUND: The aim of this study was to investigate the feasibility of ultrahypofractionated radiotherapy to the prostate bed in patients with biochemical and/or clinical relapse following radical prostatectomy who were enrolled in the prospective, observational, multicentric POPART trial (NCT04831970). METHODS: Patients with post-radical prostatectomy PSA levels of ≥0.1-2.0 ng/mL and/or local relapse at PSMA PET/CT or multiparametric MRI were treated with Linac-based SBRT on the prostate bed up to a total dose of 32.5 Gy in five fractions every other day (EQD21.5 = 74.2 Gy). Maximum acute toxicity was assessed using the Common Terminology Criteria for Adverse Events version 5 scale. International Consultation on Incontinence Questionnaire-Short Form (ICIQ-SF) and Prostate Cancer Index Composite for Clinical Practice (EPIC-CP) scores were assessed at baseline and during the follow-up. RESULTS: From April 2021 to June 2022, thirty men with a median age of 72 years (range 55-82) were enrolled in three centers. The median PSA level before RT was 0.30 ng/mL (range 0.18-1.89 ng/mL). At 3 months post-treatment, no GI or ≥2 GU side effects were reported; three patients (10%) experienced Grade 1 GU toxicity. No changes in ICIQ-SF or in the urinary domains of EPIC-CP were observed, while a transient worsening was registered in the bowel domain. At the same time point, all but two patients, who progressed distantly, were found to be biochemically controlled with a median post-treatment PSA level of 0.07 ng/mL (range 0-0.48 ng/mL). CONCLUSIONS: Our preliminary findings show that SBRT can be safely extended to the postoperative setting, without an increase in short-term toxicity or a significant decline in QoL. Long-term results are needed to confirm this strategy.

Training and validation of a knowledge-based dose-volume histogram predictive model in the optimisation of intensity-modulated proton and volumetric modulated arc photon plans for pleural mesothelioma patients.

BACKGROUND: To investigate the performance of a narrow-scope knowledge-based RapidPlan (RP) model for optimisation of intensity-modulated proton therapy (IMPT) and volumetric modulated arc therapy (VMAT) plans applied to patients with pleural mesothelioma. Second, estimate the potential benefit of IMPT versus VMAT for this class of patients. METHODS: A cohort of 82 patients was retrospectively selected; 60 were used to "train" a dose-volume histogram predictive model; the remaining 22 provided independent validation. The performance of the RP models was benchmarked, comparing predicted versus achieved mean and near-to-maximum dose for all organs at risk (OARs) in the training set and by quantitative assessment of some dose-volume metrics in the comparison of the validation RP-based data versus the manually optimised training datasets. Treatment plans were designed for a prescription dose of 44 Gy in 22 fractions (proton doses account for a fixed relative biological effectiveness RBE = 1.1). RESULTS: Training and validation RP-based plans resulted dosimetrically similar for both VMAT and IMPT groups, and the clinical planning aims were met for all structures. The IMPT plans outperformed the VMAT ones for all OARs for the contra-lateral and the mean and low dose regions for the ipsilateral OARs. Concerning the prediction performance of the RP models, the linear regression for the near-to-maximum dose resulted in Dachieved = 1.03Dpredicted + 0.58 and Dachieved = 1.02Dpredicted + 1.46 for VMAT and IMPT, respectively. For the mean dose it resulted: Dachieved = 0.99Dpredicted + 0.34 and Dachieved = 1.05Dpredicted + 0.27 respectively. In both cases, the linear correlation between prediction and achievement is granted with an angular coefficient deviating from unity for less than 5%. Concerning the dosimetric comparison between manual plans in the training cohort and RP-based plans in the validation cohort, no clinical differences were observed for the target volumes in both the VMAT and IMPT groups. Similar consistency was observed for the dose-volume metrics analysed for the OAR. This proves the possibility of achieving the same quality of plans with manual procedures (the training set) or with automated RP-based methods (the validation set). CONCLUSION: Two models were trained and validated for VMAT and IMPT plans for pleural mesothelioma. The RP model performance resulted satisfactory as measured by the agreement between predicted and achieved (after full optimisation) dose-volume metrics. The IMPT plans outperformed the VMAT plans for all the OARs (with different intensities for contra- or ipsilateral structures). RP-based planning enabled the automation of part of the optimisation and the harmonisation of the dose-volume results between training and validation. The IMPT data showed a systematic significant dosimetric advantage over VMAT. In general, using an RP-based approach can simplify the optimisation workflow in these complex treatment indications without impacting the quality of plans.

Radiomics-based prognosis classification for high-risk prostate cancer treated with radiotherapy.

OBJECTIVE: The present study aimed to investigate if CT-based radiomics features could correlate to the risk of metastatic progression in high-risk prostate cancer patients treated with radical RT and long-term androgen deprivation therapy (ADT). MATERIALS AND METHODS: A total of 157 patients were investigated and radiomics features extracted from the contrast-free treatment planning CT series. Three volumes were segmented: the prostate gland only (CTV_p), the prostate gland with seminal vesicles (CTV_psv), and the seminal vesicles only (CTV_sv). The patients were split into two subgroups of 100 and 57 patients for training and validation. Five clinical and 62 radiomics features were included in the analysis. Considering metastases-free survival (MFS) as an endpoint, the predictive model was used to identify the subgroups with favorable or unfavorable prognoses (separated by a threshold selected according to the Youden method). Pure clinical, pure radiomic, and combined predictive models were investigated. RESULTS: With a median follow-up of 30.7 months, the MFS at 1 and 3 years was 97.2% ± 1.5 and 92.1% ± 2.0, respectively. Univariate analysis identified seven potential predictors for MFS in the CTV_p group, 11 in the CTV_psv group, and 9 in the CTV_sv group. After elastic net reduction, these were 4 predictors for MFS in the CTV_p group (positive lymph nodes, Gleason score, H_Skewness, and NGLDM_Contrast), 5 in the CTV_psv group (positive lymph nodes, Gleason score, H_Skewnesss, Shape_Surface, and NGLDM_Contrast), and 6 in the CTV_sv group (positive lymph nodes, Gleason score, H_Kurtosis, GLCM_Correlation, GLRLM_LRHGE, and GLZLM_SZLGE). The patients' group of the training and validation cohorts were stratified into favorable and unfavorable prognosis subgroups. For the combined model, for CTV_p, the mean MFS was 134 ± 14.5 vs. 96.9 ± 22.2 months for the favorable and unfavorable subgroups, respectively, and 136.5 ± 14.6 vs. 70.5 ± 4.3 months for CTV_psv and 150.0 ± 4.2 vs. 91.1 ± 8.6 months for CTV_sv, respectively. CONCLUSION: Radiomic features were able to predict the risk of metastatic progression in high-risk prostate cancer. Combining the radiomic features and clinical characteristics can classify high-risk patients into favorable and unfavorable prognostic groups.

Metastatic salivary gland carcinoma: A role for stereotactic body radiation therapy? A study of AIRO-Head and Neck working group.

OBJECTIVES: The role of radiotherapy (RT) for oligometastases is currently established in different oncological settings but data on salivary gland cancer (SGC) are lacking. We evaluated the role of RT in oligometastatic SGC patients, focusing on stereotactic body radiation therapy (SBRT). MATERIALS AND METHODS: We performed a retrospective, multicentric study of oligometastatic SGC treated with palliative RT or SBRT. Endpoints included response evaluation and local control (LC). RESULTS: Between 2006 and 2016, 64 patients were collected from 9 Italian Cancer Centers, on behalf of the Italian Association of Radiotherapy and Clinical Oncology (AIRO) Head and Neck Working Group. 37 patients (57.8%) were suffering from adenoid cystic carcinoma (ACC) and 27 patients (42.2%) had non-ACC. Thirty-four patients underwent palliative RT (53,1%), and 30 received SBRT (46,9%). Most common metastatic sites were bone for palliative RT and lung for SBRT. Among patients treated with SBRT, an objective response or a stability was observed in all treated lesions. After a median follow-up of 29.2 months (range 2.3-117.1), LC at 12 months was 57.5% for patients treated with SBRT and was higher in ACC subgroup. CONCLUSION: We confirmed the potential role of SBRT in the management of oligometastatic SGC patients to control limited burden of disease considering the absence of effective systemic therapies.