In order to limit radiotherapy (RT)-related side effects, effective toxicity prediction and assessment schemes are essential. In recent years, the growing interest toward artificial intelligence and ...machine learning (ML) within the science community has led to the implementation of innovative tools in RT. Several researchers have demonstrated the high performance of ML-based models in predicting toxicity, but the application of these approaches in clinics is still lagging, partly due to their low interpretability. Therefore, an overview of contemporary research is needed in order to familiarize practitioners with common methods and strategies. Here, we present a review of ML-based models for predicting and classifying RT-induced complications from both a methodological and a clinical standpoint, focusing on the type of features considered, the ML methods used, and the main results achieved. Our work overviews published research in multiple cancer sites, including brain, breast, esophagus, gynecological, head and neck, liver, lung, and prostate cancers. The aim is to define the current state of the art and main achievements within the field for both researchers and clinicians.
Italian legislation defines stringent groundwater chemical quality criteria, to be applied at a site’s downgradient property boundary, irrespective of whether the underlying aquifer is, or could be, ...used for water resource purposes. In some scenarios, the regulatory authorities may identify less stringent standards, but this rarely occurs. This means that many sites with groundwater contamination are managed using hydraulic barriers, as source zone remediation may not achieve the stringent groundwater standards required due to technology limits or time constraints; therefore, the parties responsible for contamination often decide to continue to operate these hydraulic barriers indefinitely. This article describes the first application in Italy of source treatment using Electrical Resistance Heating (ERH), a remediation technology capable of removing a large percentage of contaminant mass, at a site where a hydraulic barrier is operating within a low yielding aquifer that is not used for water supply. The implementation of this technology was possible since the source zone was far from the downgradient site boundary, thus making achievement of the stringent quality standards at the boundary possible within a reasonable timeframe. The ERH system recovered of about 600 kg of contaminants within a timeframe of 8 months and achieved a reduction of contaminant concentrations in the most impacted areas greater than 90%. This article also emphasizes that, in similar low yielding aquifers, setting less stringent groundwater standards at the site boundary whilst still protecting downgradient receptors may promote more widespread implementation of source remediation activities in Italy.
Radiotherapy represents a highly targeted and efficient treatment choice in many cancer types, both with curative and palliative intents. Nevertheless, radioresistance, consisting in the adaptive ...response of the tumor to radiation-induced damage, represents a major clinical problem. A growing body of the literature suggests that mechanisms related to mitochondrial changes and metabolic remodeling might play a major role in radioresistance development. In this work, the main contributors to the acquired cellular radioresistance and their relation with mitochondrial changes in terms of reactive oxygen species, hypoxia, and epigenetic alterations have been discussed. We focused on recent findings pointing to a major role of mitochondria in response to radiotherapy, along with their implication in the mechanisms underlying radioresistance and radiosensitivity, and briefly summarized some of the recently proposed mitochondria-targeting strategies to overcome the radioresistant phenotype in cancer.
Paucity and low evidence-level data on proton therapy (PT) represent one of the main issues for the establishment of solid indications in the PT setting. Aim of the present registry, the POWER ...registry, is to provide a tool for systematic, prospective, harmonized, and multidimensional high-quality data collection to promote knowledge in the field of PT with a particular focus on the use of hypofractionation.
All patients with any type of oncologic disease (benign and malignant disease) eligible for PT at the European Institute of Oncology (IEO), Milan, Italy, will be included in the present registry. Three levels of data collection will be implemented: Level (1) clinical research (patients outcome and toxicity, quality of life, and cost/effectiveness analysis); Level (2) radiological and radiobiological research (radiomic and dosiomic analysis, as well as biological modeling); Level (3) biological and translational research (biological biomarkers and genomic data analysis). Endpoints and outcome measures of hypofractionation schedules will be evaluated in terms of either Treatment Efficacy (tumor response rate, time to progression/percentages of survivors/median survival, clinical, biological, and radiological biomarkers changes, identified as surrogate endpoints of cancer survival/response to treatment) and Toxicity. The study protocol has been approved by the IEO Ethical Committee (IEO 1885). Other than patients treated at IEO, additional PT facilities (equipped with Proteus®ONE or Proteus®PLUS technologies by IBA, Ion Beam Applications, Louvain-la-Neuve, Belgium) are planned to join the registry data collection. Moreover, the registry will be also fully integrated into international PT data collection networks.
Breast-conserving surgery (BCS) and whole breast radiation therapy (WBRT) are the standard of care for early-stage breast cancer (BC). Based on the observation that most local recurrences occurred ...near the tumor bed, accelerated partial breast irradiation (APBI), consisting of a higher dose per fraction to the tumor bed over a reduced treatment time, has been gaining ground as an attractive alternative in selected patients with low-risk BC. Although more widely delivered in postoperative setting, preoperative APBI has also been investigated in a limited, though increasing, and number of studies. The aim of this study is to test the feasibility, safety and efficacy of preoperative radiotherapy (RT) in a single fraction for selected BC patients.
This is a phase I/II, single-arm and open-label single-center clinical trial using CyberKnife. The clinical investigation is supported by a preplanning section which addresses technical and dosimetric issues. The primary endpoint for the phase I study, covering the 1st and 2nd year of the research project, is the identification of the maximum tolerated dose (MTD) which meets a specific target toxicity level (no grade 3-4 toxicity). The primary endpoint for the phase II study (3rd to 5th year) is the evaluation of treatment efficacy measured in terms of pathological complete response rate.
The study will investigate the response of BC to the preoperative APBI from different perspectives. While preoperative APBI represents a form of anticipated boost, followed by WBRT, different are the implications for the scientific community. The study may help to identify good responders for whom surgery could be omitted. It is especially appealing for patients unfit for surgery due to advanced age or severe co-morbidities, in addition to or instead of systemic therapies, to ensure long-term local control. Moreover, patients with oligometastatic disease synchronous with primary BC may benefit from APBI on the intact tumor in terms of tumor progression free survival. The study of response to RT can provide useful information about BC radiobiology, immunologic reactions, genomic expression, and radiomics features, to be tested on a larger scale.
The study was prospectively registered at clinicaltrials.gov ( NCT04679454 ).
Purpose
To assess outcome of breast cancer (BC) stages pT1-2 N0-1 after mastectomy alone and to identify prognostic factors calling for the need of postmastectomy radiotherapy.
Methods
Patients who ...were not eligible for breast conserving surgery (BCS) were operated on with mastectomy between 1998 and 2008. Locoregional (LRR), distant (DM) control and breast cancer specific survival (BCSS) were retrospectively evaluated. Cumulative incidence (CI) of events was estimated according to Kalbfleisch and Prentice while Gray’s test tested difference. Kaplan–Meier method for survival and Cox proportional hazards model for univariable and multivariable analysis were used. A matched pair analysis between mastectomy alone and BCS plus whole breast irradiation (WBI), using the propensity score method, was performed.
Results
1281 pT1-2 N0 and 1081 pT1-2 N1 were identified. Median follow-up was 8.2 years (9.2 years for survival). Overall, LRR rate was low for both N0 and N1 subgroups (10-year CI, 8.8% and 10.9%, respectively). Young age, lymphovascular invasion and Ki-67 ≥ 20% were proved to be statistically significant prognostic factors at multivariable analysis. The combination of ≥ 2 risk factors increased LRR rate to ≥ 15%. Risk factors combination weighed on LRR rate more than nodal status itself. DM rate doubled moving from negative to positive nodal status (10-year CI 10.5% versus 20.3%, respectively). BCSS remained high in both N0 and N1 subgroups (10-year CI 92.4% versus 84.5%, respectively). Remarkably, all the molecular subtypes except Luminal A significantly affected DM and BCSS both in the N0 and N1 subgroups. Nodes number significantly impacted on DM and BCSS but not on locoregional control. In the matched pair analysis, WBI decreased nodal recurrence rate and improved distant control, without affecting survival.
Conclusions
Selected patients, namely those with at least two additional risk factors, presented high enough LRR risk to support the use of postmastectomy radiotherapy in both N0 and N1 subgroups. Moreover, the observation that radiotherapy may provide benefits that go beyond local control deserves to be further investigated.
Currently, main treatment strategies for early-stage non-small cell lung cancer (ES-NSCLC) disease are surgery or stereotactic body radiation therapy (SBRT), with successful local control rates for ...both approaches. However, regional and distant failure remain critical in SBRT, and it is paramount to identify predictive factors of response to identify high-risk patients who may benefit from more aggressive approaches. The main endpoint of the MONDRIAN trial is to identify multi-omic biomarkers of SBRT response integrating information from the individual fields of radiomics, genomics and proteomics.
MONDRIAN is a prospective observational explorative cohort clinical study, with a data-driven, bottom-up approach. It is expected to enroll 100 ES-NSCLC SBRT candidates treated at an Italian tertiary cancer center with well-recognized expertise in SBRT and thoracic surgery. To identify predictors specific to SBRT, MONDRIAN will include data from 200 patients treated with surgery, in a 1:2 ratio, with comparable clinical characteristics. The project will have an overall expected duration of 60 months, and will be structured into five main tasks: (i) Clinical Study; (ii) Imaging/ Radiomic Study, (iii) Gene Expression Study, (iv) Proteomic Study, (v) Integrative Model Building.
Thanks to its multi-disciplinary nature, MONDRIAN is expected to provide the opportunity to characterize ES-NSCLC from a multi-omic perspective, with a Radiation Oncology-oriented focus. Other than contributing to a mechanistic understanding of the disease, the study will assist the identification of high-risk patients in a largely unexplored clinical setting. Ultimately, this would orient further clinical research efforts on the combination of SBRT and systemic treatments, such as immunotherapy, with the perspective of improving oncological outcomes in this subset of patients.
The study was prospectively registered at clinicaltrials.gov (NCT05974475).
Machine learning (ML) is emerging as a feasible approach to optimize patients' care path in Radiation Oncology. Applications include autosegmentation, treatment planning optimization, and prediction ...of oncological and toxicity outcomes. The purpose of this clinically oriented systematic review is to illustrate the potential and limitations of the most commonly used ML models in solving everyday clinical issues in head and neck cancer (HNC) radiotherapy (RT).
Electronic databases were screened up to May 2021. Studies dealing with ML and radiomics were considered eligible. The quality of the included studies was rated by an adapted version of the qualitative checklist originally developed by Luo et al. All statistical analyses were performed using R version 3.6.1.
Forty-eight studies (21 on autosegmentation, four on treatment planning, 12 on oncological outcome prediction, 10 on toxicity prediction, and one on determinants of postoperative RT) were included in the analysis. The most common imaging modality was computed tomography (CT) (40%) followed by magnetic resonance (MR) (10%). Quantitative image features were considered in nine studies (19%). No significant differences were identified in global and methodological scores when works were stratified per their task (i.e., autosegmentation).
The range of possible applications of ML in the field of HN Radiation Oncology is wide, albeit this area of research is relatively young. Overall, if not safe yet, ML is most probably a bet worth making.
This review provides a formal overview of current automatic segmentation studies that use deep learning in radiotherapy. It covers 807 published papers and includes multiple cancer sites, image types ...(CT/MRI/PET), and segmentation methods. We collect key statistics about the papers to uncover commonalities, trends, and methods, and identify areas where more research might be needed. Moreover, we analyzed the corpus by posing explicit questions aimed at providing high-quality and actionable insights, including: “What should researchers think about when starting a segmentation study?”, “How can research practices in medical image segmentation be improved?”, “What is missing from the current corpus?”, and more. This allowed us to provide practical guidelines on how to conduct a good segmentation study in today’s competitive environment that will be useful for future research within the field, regardless of the specific radiotherapeutic subfield. To aid in our analysis, we used the large language model ChatGPT to condense information.
Introduction
Reirradiation (reRT) of locally recurrent/second primary tumors of the head and neck region is a potentially curative treatment for patients not candidate to salvage surgery. Aim of the ...present study is to summarize available literature on both prognostic factors and indications to curative reRT in this clinical setting.
Materials and methods
A narrative review of the literature was performed on two topics: (1) patients’ selection according to prognostic factors and (2) dosimetric feasibility of reRT. Postoperative reRT and palliative intent treatments were out of the scope of this work.
Results
Patient-tumor and treatment-related prognostic factors were analyzed, together with dosimetric parameters concerning target volume and organs at risk. Based on available evidence, a stepwise approach has been proposed aiming to provide a useful tool to identify suitable candidates for curative reRT in clinical practice. This was then applied to two clinical cases, proposed at the end of this work.
Conclusion
A second course of RT in head and neck recurrence/second primary tumors is a personalized approach that can be offered to selected patients only in centers with expertise and dedicated equipment following a multidisciplinary team discussion.
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