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.
Standard treatment in locally-advanced cervical cancer is external beam radiotherapy concomitant with platinum-based chemotherapy, followed by brachytherapy. The goal of our study was to determine ...whether an intensity modulated radiation therapy (IMRT) boost is feasible in patients unfit for brachytherapy.
We retrospectively analyzed data of 25 patients unfit for brachytherapy with median age 55 years (range, 30-82) with locally-advanced/metastatic cervical cancer who underwent external beam radiotherapy to pelvis ±para-aortic lymph nodes and sequential IMRT boost between July 2014 and December 2017. Total dose of 45-50.4 Gy in 25-28 fractions (1.8 Gy/fraction) was administered to the cervix, uterus, parametria, ovaries, vaginal tissues (based on vaginal extension), involved lymph nodes, or relevant draining lymph-nodal groups. Para-aortic nodes were included if involved at radiological staging or if common iliac nodes were positive. The IMRT boost included all residual tumor after external beam radiotherapy identified on MRI. The Kaplan-Meier method was used to calculate 2 years' overall survival, 2 years' progression-free survival, and 2 years' local control. Overall survival- and progression-free survival were calculated considering the starting of radiotherapy or neo-adjuvant chemotherapy if prescribed, while local control was calculated from the end of radiotherapy.
Median radiation dose to pelvis ±para-aortic lymph nodes was 50.4 Gy (45-50.4), boost treatment was homogeneously performed to a total dose of 25 Gy in five fractions every other day.After a median follow-up of 26 months (range, 4-77), tumor persistence at cervix at 6 months from the end of radiotherapy or local recurrence occurred in five women (20%), eight (32%) experienced a further distant progression (two of them had also tumor persistence). Two-year local control and overall survival rates for all stages were 78% and 67%, respectively. According to Common Terminology Criteria for Adverse Events v.4 scoring criteria, 10 patients experienced gastrointestinal and/or genitourinary grade G1-2 acute toxicity. G2 rectal late toxicity requiring laser-coagulation was registered in two patients, there were no gastrointestinal and/or genitourinary acute or late toxicities≥G3.
The combination of external beam radiotherapy and brachytherapy remains the standard of care, however our preliminary data show the feasibility of IMRT boost in terms of toxicity with promising results in terms of local control and overall survival.
Adenoid cystic carcinoma/basaloid cell carcinoma of the prostate (ACC/BCC) is a very rare variant of prostate cancer with uncertain behavior. Few cases are reported in the literature. Data on ...treatment options are scarce. The aim of our work was to retrospectively review the published reports. Thirty-three case reports or case series were analyzed (106 patients in total). Pathological features, management, and follow-up information were evaluated. Despite the relatively low level of evidence given the unavoidable lack of prospective trials for such a rare prostate tumor, the following considerations were made: prostate ACC/BCC is an aggressive tumor often presenting with locally advanced disease and incidental diagnosis occurs during transurethral resection of the prostate for urinary obstructive symptoms. Prostate-specific antigen was not a reliable marker for diagnosis nor follow-up. Adequate staging with Computed Tomography (CT) scan and Magnetic Resonance Imaging (MRI) should be performed before treatment and during follow-up, while there is no evidence for the use of Positron Emission Tomography (PET). Radical surgery with negative margins and possibly adjuvant radiotherapy appear to be the treatments of choice. The response to androgen deprivation therapy was poor. Currently, there is no evidence of the use of truly effective systemic therapies.
Mediastinal or hilar lymph node metastases are a challenging condition in patients affected by solid tumors. Stereotactic body radiation therapy (SBRT) could play a crucial role in the therapeutic ...management and in the so-called "no-fly zone", delivering high doses of radiation in relatively few treatment fractions with excellent sparing of healthy surrounding tissues and low toxicity. The aim of this systematic review is to evaluate the feasibility and tolerability of SBRT in the treatment of mediastinal and hilar lesions with particular regard to the radiotherapy doses, dose constraints for organs at risk, and clinical outcomes.
Two blinded investigators performed a critical review of the Medline, Web of Knowledge, Google Scholar, Scopus, and Cochrane databases according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses statement (PRISMA), starting from a specific question: What is the clinical impact of SBRT for the treatment of oligorecurrent/oligoprogressive mediastinal and hilar metastasis? All retrospective and prospective clinical trials published in English up to February 2022 were analyzed.
A total of 552 articles were identified and 12 of them were selected with a total number of 478 patients treated with SBRT for mediastinal or hilar node recurrence. All the studies are retrospective, published between 2015 and 2021 with a median follow-up ranging from 12 to 42.2 months. Studies following SBRT for lung lesions or retreatments after thorax radiotherapy for stage III lung cancer were also included. The studies showed extensive heterogeneity in terms of patient and treatment characteristics. Non-small cell lung cancer was the most frequently reported histology. Different dose schemes were used, with a higher prevalence of 4-8 Gy in 5 or 6 fractions, but dose escalation was also used up to 52 Gy in 4 fractions with dose constraints mainly derived from RTOG 0813 trial. The radiotherapy technique most frequently used was volumetric modulated arc therapy (VMAT) with a median PTV volume ranging from 7 to 25.7 cc. The clinical outcome seems to be very encouraging with 1-year local control (LC), overall survival (OS) and progression-free survival (PFS) rates ranging from 84 to 94%, 53 to 88% and 23 to 53.9%, respectively. Half of the studies did not report toxicity greater than G3 and only five cases of fatal toxicity were reported.
From the present review, it is not possible to draw definitive conclusions because of the heterogeneity of the studies analyzed. However, SBRT appears to be a safe and effective option in the treatment of mediastinal and hilar lymph node recurrence, with a good toxicity profile. Its use in clinical practice is still limited, and there is extensive heterogeneity in patient selection and fractionation schedules. Good performance status, small PTV volume, absence of previous thoracic irradiation, and administration of a high biologically effective dose (BED) seem to be factors that correlate with greater local control and better survival rates. In the presence of symptoms related to the thoracic lymph nodes, SBRT determines a rapid control that lasts over time. We look forward to the prospective studies that are underway for definitive conclusions.
Various definitions are currently in use to describe high-risk prostate cancer. This variety in definitions is important for patient counseling, since predicted outcomes depend on which ...classification is applied to identify patient’s prostate cancer risk category. Historically, strategies for the treatment of localized high-risk prostate cancer comprise local approaches such as surgery and radiotherapy, as well as systemic approaches such as hormonal therapy. Nevertheless, since high-risk prostate cancer patients remain the group with higher-risk of treatment failure and mortality rates, nowadays, novel treatment strategies, comprising hypofractionated-radiotherapy, second-generation antiandrogens, and hadrontherapy, are being explored in order to improve their long-term oncological outcomes. This narrative review aims to report the current management of high-risk prostate cancer and to explore the future perspectives in this clinical setting.
Breast cancer represents the second leading cause of cancer-related death in the female population, despite continuing advances in treatment options that have significantly accelerated in recent ...years. Conservative treatments have radically changed the concept of healing, also focusing on the psychological aspect of oncological treatments. In this scenario, radiotherapy plays a key role. Brachytherapy is an extremely versatile radiation technique that can be used in various settings for breast cancer treatment. Although it is invasive, technically complex, and requires a long learning curve, the dosimetric advantages and sparing of organs at risk are unequivocal. Literature data support muticatheter interstitial brachytherapy as the only method with strong scientific evidence to perform partial breast irradiation and reirradiation after previous conservative surgery and external beam radiotherapy, with longer follow-up than new, emerging radiation techniques, whose effectiveness is proven by over 20 years of experience. The aim of our work is to provide a comprehensive view of the use of interstitial brachytherapy to perform breast lumpectomy boost, breast-conserving accelerated partial breast irradiation, and salvage reirradiation for ipsilateral breast recurrence, with particular focus on the implant description, limits, and advantages of the technique.
Radio-chemotherapy with CDDP is the standard for H&N squamous cell cancer. CDDP 100 mg/m
/q3 is the standard; alternative schedules are used to reduce toxicity, mostly 40 mg/m
/q1.
Patients were ...treated from 1/2010 to 1/2017 in two Radiation Oncology Centres. Propensity score analysis (PS) was retrospectively used to compare these two schedules.
Patients analyzed were 166. Most (114/166) had 1w-CDDP while 52 had 3w-CDDP. In the 3w-CDDP group, patients were younger, with better performance status, smaller disease extent and a more common nodal involvement than in the 1w-CDDP. Acute toxicity was similar in the groups. Treatment compliance was lower in the w-CCDP. Overall survival before PS was better for female, for oropharyngeal disease and for 3w-CDDP group. After PS, survival was not related to the CDDP schedule.
3w-CDDP remains the standard for fit patients, weekly schedule could be safely used in selected patients.
Prostate cancer (PCa) is the second most common cancer among men. New imaging-modalities have increased the diagnosed patients with limited number of metastasis after primary curative therapy, ...introducing so-called oligometastatic state. Stereotactic body radiotherapy (SBRT) is emerging as a low-toxicity treatment to erase PCa localizations and postpone androgen deprivation therapy (ADT). A deeper understanding of the predictive role of biomarkers is desirable for a targeted treatment selection and surveillance programs. The aims of the RADIOSA trial are: 1. Compare SBRT +/- ADT for oligorecurrent-castration-sensitive PCa (OCS-PCa) in terms of efficacy, toxicity and Quality of Life (QoL). 2. Develop biology/imaging based prognostic tool that allows identifying OCS-PCa subclasses.
This is a randomized phase II clinical trial, recruiting 160 OCS-PCa in 3 years, with progression-free survival (PFS) as primary endpoint. Three tasks will be developed: 1. Randomized clinical study (3 years for accrual and 2 years for follow-up and data analysis); 2. Imaging study, including imaging registration and METastasis Reporting and Data System (MET-RADS) criteria; 3. Pre-clinical study, development of a biobank of blood samples for the analysis of neutrophil-to-lymphocyte ratio and preparatory for a subsequent miRNA profiling. We aim to determine which arm is justified for testing in a subsequent Phase III trial. A decision-tree algorithm, based on prognosis, biological phenotype and imaging profile, will be developed.
Recruiting will start in July 2019. SBRT will allow obtaining excellent PFS, local control, QoL and low toxicity. In SBRT arm, ADT deferral will allow for a drug-holiday, delaying the detrimental impact on QoL. A sufficient number of blood samples will be collected to perform biological patient profiling. A stratification tool will be established with an analysis of morphological and functional imaging, based on the use of MET-RADS criteria. So, in conclusion, RADIOSA aims to define the optimal management of bone/nodal PCa relapses in a SBRT regimen. This study will increase our knowledge on low-burden metastatic PCa in the era of high precision and high technology personalized medicine, offering highly effective therapy in terms of clinical outcome and cost-effectiveness.
The RADIOSA study was prospectively registered at clinicaltrials.gov ( NCT03940235 , May 2019).
In recent years, a growing interest has been directed towards oligometastatic prostate cancer (OMPC), as patients with three to five metastatic lesions have shown a significantly better survival as ...compared with those harboring a higher number of lesions. The efficacy of local ablative treatments directed on metastatic lesions (metastases-directed treatments) was extensively investigated, with the aim of preventing further disease progression and delaying the start of systemic androgen deprivation therapies. Definitive diagnosis of prostate cancer is traditionally based on histopathological analysis. Nevertheless, a bioptic sample—static in nature—inevitably fails to reflect the dynamics of the tumor and its biological response due to the dynamic selective pressure of cancer therapies, which can profoundly influence spatio-temporal heterogeneity. Furthermore, even with new imaging technologies allowing an increasingly early detection, the diagnosis of oligometastasis is currently based exclusively on radiological investigations. Given these premises, the development of minimally-invasive liquid biopsies was recently promoted and implemented as predictive biomarkers both for clinical decision-making at pre-treatment (baseline assessment) and for monitoring treatment response during the clinical course of the disease. Through liquid biopsy, different biomarkers, commonly extracted from blood, urine or saliva, can be characterized and implemented in clinical routine to select targeted therapies and assess treatment response. Moreover, this approach has the potential to act as a tissue substitute and to accelerate the identification of novel and consistent predictive analytes cost-efficiently. However, the utility of tumor profiling is currently limited in OMPC due to the lack of clinically validated predictive biomarkers. In this scenario, different ongoing trials, such as the RADIOSA trial, might provide additional insights into the biology of the oligometastatic state and on the identification of novel biomarkers for the outlining of true oligometastatic patients, paving the way towards a wider ideal approach of personalized medicine. The aim of the present narrative review is to report the current state of the art on the solidity of liquid biopsy-related analytes such as CTCs, cfDNA, miRNA and epi-miRNA, and to provide a benchmark for their further clinical implementation. Arguably, this kind of molecular profiling could refine current developments in the era of precision oncology and lead to more refined therapeutic strategies in this subset of oligometastatic patients.
This study represents a descriptive analysis of preliminary results of a Phase II trial on a novel mixed beam radiotherapy (RT) approach, consisting of carbon ions RT (CIRT) followed by ...intensity-modulated photon RT, in combination with hormonal therapy, for high-risk prostate cancer (HR PCa) with a special focus on acute toxicity.
Primary endpoint was the evaluation of safety in terms of acute toxicity. Secondary endpoints were early and long-term tolerability of treatment, quality of life (QoL), and efficacy. Data on acute and late toxicities were collected according to RTOG/EORTC. QoL of enrolled patients was assessed by IPSS, EORTC QLQ-C30, EORTC QLQ-PR25, and sexual activity by IIEF-5.
Twenty-six patients were enrolled in the study, but only 15 completed so far the RT course and were included. Immediately after CIRT, no patients experienced GI/GU toxicity. At 1 and 3 months from the whole course RT completion, no GI/GU toxicities greater than grade 2 were observed. QoL scores were overall satisfactory.
The feasibility of the proposed mixed treatment schedule was assessed, and an excellent acute toxicity profile was recorded. Such findings instil confidence in the continuation of this mixed approach, with evaluation of long-term tolerability and efficacy.
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