Recent Applications of Artificial Intelligence in Radiotherapy: Where We Are and Beyond

In recent decades, artificial intelligence (AI) tools have been applied in many medical fields, opening the possibility of finding novel solutions for managing very complex and multifactorial problems, such as those commonly encountered in radiotherapy (RT). We conducted a PubMed and Scopus search to identify the AI application field in RT limited to the last four years. In total, 1824 original papers were identified, and 921 were analyzed by considering the phase of the RT workflow according to the applied AI approaches. AI permits the processing of large quantities of information, data, and images stored in RT oncology information systems, a process that is not manageable for individuals or groups. AI allows the iterative application of complex tasks in large datasets (e.g., delineating normal tissues or finding optimal planning solutions) and might support the entire community working in the various sectors of RT, as summarized in this overview. AI-based tools are now on the roadmap for RT and have been applied to the entire workflow, mainly for segmentation, the generation of synthetic images, and outcome prediction. Several concerns were raised, including the need for harmonization while overcoming ethical, legal, and skill barriers

Use of Radium-223 Dichloride in Patients With Osteonecrosis of the Jaw Induced by Zoledronic Acid: Report of 2 Cases.

Bisphosphonates, a group of inorganic pyrophosphate analogues that prevent the loss of bone density, are commonly used in patients with bone metastases; the calcium-mimetic a-emitter radium-223 dichloride (Ra223) is a bone-targeting therapy used in patients with metastatic castration-resistant prostate cancer (mCRPC)-related bone metastases. Both treatments reduce pain and disability; Ra223 is associated with significantly improved overall survival in mCRPC. Patients who receive bisphosphonate therapy are at risk of developing osteonecrosis of the jaw, especially in those who do not undergo an accurate oral evaluation and sanitation before the beginning of therapy, and in patients who present with conditions that facilitate the development of this problem, such as inadequate oral and dental care, lack of prophylactic antimicrobial mouth rinsing, patient comorbidity, or suboptimal suturing after tooth extraction. Although there is possible synergism between bisphosphonates and Ra223 therapy, there is no consensus about the use of Ra223 in patients with previous/current osteonecrosis of the jaw induced by zoledronic acid. However, our experience suggests that Ra223 therapy might not be contraindicated in patients with osteonecrosis of the jaw induced by zoledronic acid if an appropriate multidisciplinary approach is followed, and we report 2 cases of patients with current or previous osteonecrosis of the jaw induced by zoledronic acid, who were treated with Ra223 for mCRPCrelated bone metastases. Multidisciplinary management, including accurate clinical and radiological evaluation before beginning therapy with Ra223, together with oral sanitation and periodic controls during treatment, allowed successful administration of Ra223 while reducing side effects, with absent or minimal worsening of osteonecrosis

Improving the Integration between Palliative Radiotherapy and Supportive Care: A Narrative Review

Palliative radiotherapy (PRT) is known to be effective in relieving cancer related symptoms. However, many studies and clinical practice show several barriers hindering its use and worsening the quality of patient support during PRT. Various solutions were proposed to overcome these barriers: training on PRT for supportive and palliative care specialists and training on palliative care for radiation oncologists, and introduction of pathways and organizational models specifically dedicated to PRT. Evidence on innovative organizational models and mutual training experiences is few and sparse. Therefore, the aim of this literature review is to present a quick summary of the information available on improving the PRT quality through training, new pathways, and innovative organizational models. The majority of studies on the integration of PRT with other palliative and supportive therapies present low levels of evidence being mostly retrospective analyses. However, it should be emphasized that all reports uniformly showed advantages coming from the integration of PRT with supportive therapies. To actively participate in the integration of PRT and palliative care, providing comprehensive support to the needs of patients with advanced cancer, radiation oncologists should not only plan PRT but also: (i) assess and manage symptoms and stress, (ii) rapidly refer patients to specialists in management of more complex symptoms, and (iii) participate in multidisciplinary palliative care teams. To this end, improved education in palliative care both in residency schools and during professional life through continuous medical education is clearly needed. In particular, effective training is needed for radiotherapy residents to enable them to provide patients with comprehensive palliative care. Therefore, formal teaching of adequate duration, interactive teaching methods, attendance in palliative care services, and education in advanced palliative care should be planned in post-graduated schools of radiotherapy

CARE-compliant stereotactic radiotherapy of urothelial nodal metastases: A case report

The aim of the present study was to report the case of a 58-year-old male patient with ureteral carcinoma who underwent ureteroileostomy treatment. At 2 years following surgery, six lymph node metastases (LNMs) were detected in the patient's para-aortic and pelvic regions using F-18-labeled fluoro-2-deoxyglucose (FDG) positron emission tomography (PET)/CT. All LNMs were treated using stereotactic body radiotherapy (SBRT; 35-40 Gy/5 fractions). At 3 months after radiotherapy, F-18-FDG-PET/CT examination revealed a complete radiological and metabolic response of all targeted treatment sites in the patient. In the 2 years following radiotherapy, another three same-dose SBRT treatments were performed on single or multiple LNMs, which were all detected in the abdomen and pelvis of the patient. Overall, a total of 11 LNMs were targeted in the patient and all exhibited complete radiological and metabolic response following treatment. The only treatment side effect reported by the patient was a slight and temporary loss of appetite. In patients with lymph node oligometastases there are two options for radiotherapy: i) Irradiation focusing on LNMs alone; and ii) prophylactic irradiation of the entire lymph node area combined with a boost on macroscopic lesions. In the patient discussed in the present study, the choice of irradiation focusing on LNMs alone made it possible to postpone systemic therapies and instead use an optimally tolerated treatment. The treatment outcome in this patient indicated that there was no radioresistance of urothelial LNMs

Stereotactic radiotherapy of nodal oligometastases from prostate cancer: a prisma-compliant systematic review

Androgen deprivation therapy (ADT) is the standard treatment of metastatic prostate cancer (PCa). However, metastases-directed therapies can delay the initiation or switch of systemic treatments and allow local control (LC) and prolonged progression-free survival (PFS), particularly in patients with lymph nodes (LN) oligometastases. We performed a systematic review on stereotactic body radiotherapy (SBRT) in this setting. Papers reporting LC and/or PFS were selected. Data on ADT-free survival, overall survival, and toxicity were also collected from the selected studies. Fifteen studies were eligible (414 patients), 14 of them were retrospective analyses. A high heterogeneity was observed in terms of patient selection and treatment. In one study SBRT was delivered as a single 20 Gy fraction, while in the others the median total dose ranged between 24 and 40 Gy delivered in 3-6 fractions. LC and PFS were reported in 15 and 12 papers, respectively. LC was reported as a crude percentage in 13 studies, with 100% rate in seven and 63.2-98.0% in six reports. Five studies reported actuarial LC (2-year LC: 70.0-100%). PFS was reported as a crude rate in 11 studies (range 27.3-68.8%). Actuarial 2-year PFS was reported in four studies (range 30.0-50.0%). SBRT tolerability was excellent, with only two patients with grade 3 acute toxicity and two patients with grade 3 late toxicity. SBRT for LN oligorecurrences from PCa in safe and provides optimal LC. However, the long-term effect on PFS and OS is still unclear as well as which patients are the best candidate for this approach

Machine-learning prediction model for acute skin toxicity after breast radiation therapy using spectrophotometry

PurposeRadiation-induced skin toxicity is a common and distressing side effect of breast radiation therapy (RT). We investigated the use of quantitative spectrophotometric markers as input parameters in supervised machine learning models to develop a predictive model for acute radiation toxicity.Methods and materialsOne hundred twenty-nine patients treated for adjuvant whole-breast radiotherapy were evaluated. Two spectrophotometer variables, i.e. the melanin (IM) and erythema (IE) indices, were used to quantitatively assess the skin physical changes. Measurements were performed at 4-time intervals: before RT, at the end of RT and 1 and 6 months after the end of RT. Together with clinical covariates, melanin and erythema indices were correlated with skin toxicity, evaluated using the Radiation Therapy Oncology Group (RTOG) guidelines. Binary group classes were labeled according to a RTOG cut-off score of ≥ 2. The patient’s dataset was randomly split into a training and testing set used for model development/validation and testing (75%/25% split). A 5-times repeated holdout cross-validation was performed. Three supervised machine learning models, including support vector machine (SVM), classification and regression tree analysis (CART) and logistic regression (LR), were employed for modeling and skin toxicity prediction purposes.ResultsThirty-four (26.4%) patients presented with adverse skin effects (RTOG ≥2) at the end of treatment. The two spectrophotometric variables at the beginning of RT (IM,T0 and IE,T0), together with the volumes of breast (PTV2) and boost surgical cavity (PTV1), the body mass index (BMI) and the dose fractionation scheme (FRAC) were found significantly associated with the RTOG score groups (p<0.05) in univariate analysis. The diagnostic performances measured by the area-under-curve (AUC) were 0.816, 0.734, 0.714, 0.691 and 0.664 for IM, IE, PTV2, PTV1 and BMI, respectively. Classification performances reported precision, recall and F1-values greater than 0.8 for all models. The SVM classifier using the RBF kernel had the best performance, with accuracy, precision, recall and F-score equal to 89.8%, 88.7%, 98.6% and 93.3%, respectively. CART analysis classified patients with IM,T0 ≥ 99 to be associated with RTOG ≥ 2 toxicity; subsequently, PTV1 and PTV2 played a significant role in increasing the classification rate. The CART model provided a very high diagnostic performance of AUC=0.959.ConclusionsSpectrophotometry is an objective and reliable tool able to assess radiation induced skin tissue injury. Using a machine learning approach, we were able to predict grade RTOG ≥2 skin toxicity in patients undergoing breast RT. This approach may prove useful for treatment management aiming to improve patient quality of life

Monitoring of hadrontherapy treatments by means of charged particle detection

The interaction of the incoming beam radiation with the patient body in hadrontherapy treatments produces secondary charged and neutral particles, whose detection can be used for monitoring purposes and to perform an on-line check of beam particle range. In the context of ion-therapy with active scanning, charged particles are potentially attractive since they can be easily tracked with a high efficiency, in presence of a relatively low background contamination. In order to verify the possibility of exploiting this approach for in-beam monitoring in ion-therapy, and to guide the design of specific detectors, both simulations and experimental tests are being performed with ion beams impinging on simple homogeneous tissue-like targets (PMMA). From these studies, a resolution of the order of few millimeters on the single track has been proven to be sufficient to exploit charged particle tracking for monitoring purposes, preserving the precision achievable on longitudinal shape. The results obtained so far show that the measurement of charged particles can be successfully implemented in a technology capable of monitoring both the dose profile and the position of the Bragg peak inside the target and finally lead to the design of a novel profile detector. Crucial aspects to be considered are the detector positioning, to be optimized in order to maximize the available statistics, and the capability of accounting for the multiple scattering interactions undergone by the charged fragments along their exit path from the patient body. The experimental results collected up to now are also valuable for the validation of Monte Carlo simulation software tools and their implementation in Treatment Planning Software packages

A SHort course Accelerated RadiatiON therapy (SHARON) dose-escalation trial in older adults head and neck non-melanoma skin cancer

Objectives: To assess feasibility and safety of a SHort-course Accelerated RadiatiON therapy (SHARON) regimen, in the treatment of non-melanoma skin cancers (NMSC) in older patients.Methods: Old patients (age >= 80 years) with histological confirmed non-melanoma skin cancers were enrolled. The primary endpoint was to determine the maximum tolerated dose (MTD). Radiotherapy regimen was based on the delivery of four radiotherapy fractions (5 Gy per fraction) with a twice daily fractionation in two consecutive days, Three different level of dose were administered: 20 Gy (one cycle), 40 Gy (two cycles) and 60 Gy (three cycles).Results: Thirty patients (median age: 91 years; range: 80-96) were included in this analysis, Among fourteen patients who completed the one cycle, only one (7%) experimented acute G4 skin toxicity. Twelve patients reported an improvement or resolution of baseline symptoms (overall palliative response rate: 85.8%). Nine and seven patients underwent to two and three RT cycles, respectively: of these, no G3 toxicities were recorded. The overall response rate was 100% when three cycles were delivered. The overall six-month symptom-free survival was 787% and 77.8% in patients treated with one course and more courses, respectively.Conclusions: Short-course accelerated radiotherapy in older patients with non-melanoma skin cancers is well tolerated. High doses seem to be more effective in terms of response rate.Advances in knowledge: This approach could represent an option for older adults with NMSC, being both palliative (one course) or potentially curative (more courses) in the aim, accordingly to the patient's condition

Electrochemotherapy in Vulvar Cancer and Cisplatin Combined with Electroporation. Systematic Review and In Vitro Studies

Electrochemotherapy (ECT) is an emerging treatment for solid tumors and an attractive research field due to its clinical results. This therapy represents an alternative local treatment to the standard ones and is based on the tumor-directed delivery of non-ablative electrical pulses to maximize the action of specific cytotoxic drugs such as cisplatin (CSP) and bleomycin (BLM) and to promote cancer cell death. Nowadays, ECT is mainly recommended as palliative treatment. However, it can be applied to a wide range of superficial cancers, having an impact in preventing or delaying tumor progression and therefore in improving quality of life. In addition, during the natural history of the tumor, early ECT may improve patient outcomes. Our group has extensive clinical and research experience on ECT in vulvar tumors in the palliative setting, with 70% overall response rate. So far, in most studies, ECT was based on BLM. However, the potential of CSP in this setting seems interesting due to some theoretical advantages. The purpose of this report is to: (i) compare the efficacy of CSP and BLM-based ECT through a systematic literature review; (ii) report the results of our studies on CSP-resistant squamous cell tumors cell lines and the possibility to overcome chemoresistance using ECT; (iii) discuss the future ECT role in gynecological tumors and in particular in vulvar carcinoma

Immunosuppressive treatment and radiotherapy in kidney transplant patients: A systematic review

BACKGROUND Immunosuppression (IS) therapy may contribute to cancer development. Some authors have proposed to reduce immunosuppression drugs dose in case of viral infections, in immunosuppression-related diseases, and in patients undergoing radiotherapy. The present analysis reports the results of a systematic review on kidney transplant recipients undergoing immunosuppression and radiotherapy. AIM To define if it is necessary reduce immunosuppression drugs during radiotherapy. METHODS The literature search was based on three electronic databases (Pubmed, Scopus, and Web of Science) using selected keywords linked through the "AND " and "OR " Boolean operators to build specific strings for each electronic search engine. Two researchers independently screened the citations, and disagreement was resolved by discussion or through the intervention of a third author. The review was conducted and reported according to the PRISMA statement. Extracted data were narratively synthesized, and, where possible, frequencies, percentages, and ranges were calculated. RESULTS The literature search resulted in 147 citations. After abstracts screening, 21 records were selected for full-text evaluation. Fifteen of these were excluded, leaving six papers considered suitable for analysis. There is still no clear evidence that withdrawing antimetabolites and/or calcineurin inhibitors and/or mammalian target of rapamycin-inhibitors, as opposed to continuing maintenance IS, improves patient survival in kidney transplant recipients with cancer undergoing radiotherapy. Only few retrospective studies on small cancer patient cohorts are available in this setting, but without comparison of different immunosuppression treatments. Even where immunosuppression therapy was described, patient survival seemed to be correlated only with cancer stage and type. CONCLUSION The results of this systematic review do not support the reduction of immunosuppression dose in patients undergoing radiotherapy