STereotactic Arrhythmia Radioablation (STAR): the Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary consortium (STOPSTORM.eu) and review of current patterns of STAR practice in Europe.

The EU Horizon 2020 Framework-funded Standardized Treatment and Outcome Platform for Stereotactic Therapy Of Re-entrant tachycardia by a Multidisciplinary (STOPSTORM) consortium has been established as a large research network for investigating STereotactic Arrhythmia Radioablation (STAR) for ventricular tachycardia (VT). The aim is to provide a pooled treatment database to evaluate patterns of practice and outcomes of STAR and finally to harmonize STAR within Europe. The consortium comprises 31 clinical and research institutions. The project is divided into nine work packages (WPs): (i) observational cohort; (ii) standardization and harmonization of target delineation; (iii) harmonized prospective cohort; (iv) quality assurance (QA); (v) analysis and evaluation; (vi, ix) ethics and regulations; and (vii, viii) project coordination and dissemination. To provide a review of current clinical STAR practice in Europe, a comprehensive questionnaire was performed at project start. The STOPSTORM Institutions' experience in VT catheter ablation (83% ≥ 20 ann.) and stereotactic body radiotherapy (59% > 200 ann.) was adequate, and 84 STAR treatments were performed until project launch, while 8/22 centres already recruited VT patients in national clinical trials. The majority currently base their target definition on mapping during VT (96%) and/or pace mapping (75%), reduced voltage areas (63%), or late ventricular potentials (75%) during sinus rhythm. The majority currently apply a single-fraction dose of 25 Gy while planning techniques and dose prescription methods vary greatly. The current clinical STAR practice in the STOPSTORM consortium highlights potential areas of optimization and harmonization for substrate mapping, target delineation, motion management, dosimetry, and QA, which will be addressed in the various WPs.

Stage I-II nodular lymphocyte-predominant Hodgkin lymphoma: a multi-institutional study of adult patients by ILROG.

Nodular lymphocyte-predominant Hodgkin lymphoma (NLPHL) is an uncommon histologic variant, and the optimal treatment of stage I-II NLPHL is undefined. We conducted a multicenter retrospective study including patients ≥16 years of age with stage I-II NLPHL diagnosed from 1995 through 2018 who underwent all forms of management, including radiotherapy (RT), combined modality therapy (CMT; RT+chemotherapy [CT]), CT, observation after excision, rituximab and RT, and single-agent rituximab. End points were progression-free survival (PFS), freedom from transformation, and overall survival (OS) without statistical comparison between management groups. We identified 559 patients with median age of 39 years: 72.3% were men, and 54.9% had stage I disease. Median follow-up was 5.5 years (interquartile range, 3.1-10.1). Five-year PFS and OS in the entire cohort were 87.1% and 98.3%, respectively. Primary management was RT alone (n = 257; 46.0%), CMT (n = 184; 32.9%), CT alone (n = 47; 8.4%), observation (n = 37; 6.6%), rituximab and RT (n = 19; 3.4%), and rituximab alone (n = 15; 2.7%). The 5-year PFS rates were 91.1% after RT, 90.5% after CMT, 77.8% after CT, 73.5% after observation, 80.8% after rituximab and RT, and 38.5% after rituximab alone. In the RT cohort, but not the CMT cohort, variant immunoarchitectural pattern and number of sites >2 were associated with worse PFS (P < .05). Overall, 21 patients (3.8%) developed large-cell transformation, with a significantly higher transformation rate in those with variant immunoarchitectural pattern (P = .049) and number of involved sites >2 (P = .0006). OS for patients with stage I-II NLPHL was excellent after all treatments.

Definitive radiotherapy for localized follicular lymphoma staged by 18F-FDG PET-CT: a collaborative study by ILROG.

Radiotherapy (RT) can be curative in patients with localized follicular lymphoma (FL), with historical series showing a 10-year disease-free survival of 40 to 50%. As 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography with computerized tomography (PET-CT) upstages 10 to 60% of patients compared to CT, we sought to evaluate outcomes in patients staged by PET-CT, to determine if more accurate staging leads to better patient selection and results. We conducted a multicenter retrospective study under the direction of the International Lymphoma Radiation Oncology Group (ILROG). Inclusion criteria were: RT alone for untreated stage I to II FL (grade 1-3A) with dose equivalent ≥24 Gy, staged by PET-CT, age ≥18 years, and follow-up ≥3 months. End points were freedom from progression (FFP), local control, and overall survival (OS). A total of 512 patients treated between 2000 and 2017 at 16 centers were eligible for analysis; median age was 58 years (range, 20-90); 410 patients (80.1%) had stage I disease; median RT dose was 30 Gy (24-52); and median follow-up was 52 months (3.2-174.6). Five-year FFP and OS were 68.9% and 95.7%. For stage I, FFP was 74.1% vs 49.1% for stage II (P < .0001). Eight patients relapsed in-field (1.6%). Four had marginal recurrences (0.8%) resulting in local control rate of 97.6%. On multivariable analysis, stage II (hazard ratio [HR], 2.11; 95% confidence interval [CI], 1.44-3.10) and BCL2 expression (HR, 1.62; 95% CI, 1.07-2.47) were significantly associated with less favorable FFP. Outcome after RT in PET-CT staged patients appears to be better than in earlier series, particularly in stage I disease, suggesting that the curative potential of RT for truly localized FL has been underestimated.

Applying radiation protection and safety in radiotherapy.

Radiotherapy is one of the primary treatment options in cancer management. Modern radiotherapy includes complex processes requiring many different kinds of expertise. Among them, knowledge and skills are needed in clinical oncology, radiobiology, radiotherapy planning and simulation, dose measurement and calculation, radiation safety and medical physics. Radiation oncologists should assume the full and final responsibility for treatment, follow-up and supportive care of the patient. For all these activities, radiation oncologist should coordinate and collaborate with a team including different professionals: nurses, radiographers (RTT), clinical engineers, information system experts, taking advantage in particular of the dosimetry expertise of the medical physicist. Radiation therapy is widely recognized to be one of the safest areas of modern medicine, and errors are very rare. However, radiation protection recommendations developed at national level should comply with the EURATOM Directive 2013/59. This paper describes several contemporary and emerging concerns related to radioprotection in radiation therapy including quality and safety in external beam radiotherapy and brachytherapy, foetal dose, secondary malignancies, and the safety issues related to the new techniques and treatment strategies.

Optimal Therapy for Early-Stage Hodgkin's Lymphoma: Risk Adapting, Response Adapting, and Role of Radiotherapy.

PURPOSE OF REVIEW: The aim of this article is to discuss the current role of radiotherapy (RT) for early-stage Hodgkin's lymphoma (HL) in the context of risk-adapted and response-adapted treatment strategy, and describe changes in RT technical approach. RECENT FINDINGS: In low-risk patients, RT could be omitted but, at the price of a lower progression-free survival, and its role is still debated. Ongoing trials are combining new agents with chemotherapy alone or response-adapted combined modality therapy, and results are awaited. Modern RT incorporates lower doses and smaller fields, together with the implementation of sophisticated delivery techniques aimed to reducing the dose to critical structures such as the heart. The role of RT for early-stage HL is still under debate, and new combinations are emerging; an individualized approach should be recommended, considering all RT technical opportunities to minimize toxicity while maintaining efficacy.

Three-dimensional ultrasound-based image-guided hypofractionated radiotherapy for intermediate-risk prostate cancer: results of a consecutive case series.

External beam radiotherapy (EBRT) is a standard of care in the treatment of prostate cancer. Hypofractionation is a valid option either radiobiologically and logistically in this context. Image-guidance procedures are strongly needed to provide ballistic precision to radiation delivery. The Clarity platform allows for the acquisition of three-dimensional ultrasound scans (3D-US) to perform image-guided radiotherapy. We treated a consecutive series of intermediate-risk prostate cancer patients (according to NCCN stratification) with a hypofractionated schedule (70.2 Gy/26 fractions at 2.7 Gy/daily to the prostate gland excluding the seminal vesicles at 62.1 Gy) under 3D-US guidance with the Clarity platform. The 3-year biochemical-relapse-free survival, distant-metastases-free, cancer-specific and overall survival were 98.6% (CI: 91.1-99.6%), 98.6% (CI: 91.1-99.6%), 97.5% (CI: 94.5-99.1%), and 94.3% (CI: 90.4-96.7%), respectively. Maximum detected acute GU toxicity was G0 in 22 patients (29.7%), G1 in 30 (22.7%), G2 in 19 (25.6%), G3 in 3 (4%). Maximum detected acute GI toxicity at the end of EBRT was G0 in 42 patients (56.8%), G1 in 22 (29.7%), G2 in 9 (12.1%), G3 in 1 (1.4%). The 3-year actuarial rates of ≥ G2 late toxicities were 6.1% for genito-urinary and 8.9% for gastrointestinal. The whole image-guidance workflow resulted in being robust and reliable. EBRT delivered employing a hypofractionated schedule under 3D-US-based image guidance proved to be a safe and effective treatment approach with consistent biochemical control and a mild toxicity profile. Hence, it has been transferred into daily clinical practice in our Department.

Impact of the observers' experience on daily prostate localization accuracy in ultrasound-based IGRT with the Clarity platform.

The aim of this study is to evaluate the accuracy of daily prostate localization with ultrasound imaging of various radiation oncologists with nonhomogeneous expertise. For ten patients who underwent radical radiotherapy for localized prostate cancer, 11 radiation oncologists reviewed daily ultrasound scans acquired during three different treatment sessions. The average values of two senior radiation oncologists, considered to be expert observers, were selected as reference. The remaining nine observers were divided into two groups, Group 1 and Group 2, with more and less than one year of experience, respectively. The recorded shifts in prostate position were divided in three classes: <3 mm, 3-5 mm, and > 5 mm. Deviations from reference were less than 3 mm in all directions in 91% and 81% of measurements in Groups 1 and 2, respectively. The maximum difference in terms of root mean square error (RMSE) was reported for superior-inferior (SI) direction, in particular a mean difference of 3.24 mm was observed for Group 2 in respect to the reference; moreover RMSE was 1 and 1.3 mm higher for Group 2 for anterior-posterior (AP) and left-right (LR) directions, respectively. The difference between Groups 1 and 2 was significant (p < 0.01) for all directions. The mean values for the shifts in all three directions between Group 1 and the references were 0.235 mm, 0.385 mm, and 0.009 mm for the LR, SI, and AP directions, respectively. The position of the prostate gland is more easily detectable (p = 0.956) in the AP direction, while the visibility is lower for LR (p = 0.105) and SI boundaries (p < 0.05). The observers' experience is essential for positioning the target correctly; therefore, a training period is recommended before putting the system into clinical practice.

Maintain Efficacy and Spare Toxicity: Traditional and New Radiation-Based Conditioning Regimens in Hematopoietic Stem Cell Transplantation.

Novelty in total body irradiation (TBI) as part of pre-transplant conditioning regimens lacked until recently, despite the developments in the field of allogeneic stem cell transplants. Long-term toxicities have been one of the major concerns associated with TBI in this setting, although the impact of TBI is not so easy to discriminate from that of chemotherapy, especially in the adult population. More recently, lower-intensity TBI and different approaches to irradiation (namely, total marrow irradiation, TMI, and total marrow and lymphoid irradiation, TMLI) were implemented to keep the benefits of irradiation and limit potential harm. TMI/TMLI is an alternative to TBI that delivers more selective irradiation, with healthy tissues being better spared and the control of the radiation dose delivery. In this review, we discussed the potential radiation-associated long-term toxicities and their management, summarized the evidence regarding the current indications of traditional TBI, and focused on the technological advances in radiotherapy that have resulted in the development of TMLI. Finally, considering the most recent published trials, we postulate how the role of radiotherapy in the setting of allografting might change in the future.

Association of Clinical, Tumor, and Treatment Characteristics With Seizure Control in Patients With IDH1/2-Mutant Lower-Grade Glioma.

BACKGROUND AND OBJECTIVES: Patients with IDH1/2-mutant lower-grade glioma have a high frequency of seizures. We aimed to investigate the correlations between seizures and tumor/patient characteristics and the impact of surgery and adjuvant treatments (AT) on seizure control along the disease trajectory. METHODS: We retrospectively included patients with IDH1/2-mutant lower-grade glioma who underwent surgery at the neurosurgery divisions of the University of Turin and Milan and were treated at the Division of Neuro-Oncology of Turin. Inclusion criteria were a diagnosis according to the 2021 WHO Classification and presentation with seizures; exclusion criteria were presence of CDKN2A/B homozygous deletion, intense/ring contrast enhancement on MRI at presentation, and small tissue biopsy. We evaluated seizure freedom for 2 months after surgery, 6 months from starting observation or AT, at recurrence, and for 6 months after treatments of recurrence. RESULTS: We included 150 patients. There were 77 (51%) and 31 (21%) patients with IDH-mutant/1p19q-codeleted grade 2 and 3 oligodendroglioma and 30 (20%) and 12 (8%) with IDH-mutant grade 2 and 3 astrocytoma, respectively. Total resection was accomplished in 68 (45%). Seventy-five patients (50%) received AT while the remaining 75 were observed with MRI. After 6 months after AT, 28 of 29 patients (96.5%) displayed seizure reduction, 5 of 28 (18%) being seizure-free. 66 of 124 patients (53%) had seizures at recurrence. After 6 months after second-line treatments, 60 of 66 patients (91%) had seizure reduction, 11 (17%) being seizure-free. In multivariable analyses, grade 3 histology positively correlated with seizure freedom at 2 months after surgery (OR 3.5, 1.4-8.9, p = 0.008), 6 months after AT (OR 9.0, 1.5-54.9, p = 0.017), and 6 months after treatment of recurrence (OR 4.9, 1.5-16.5, p = 0.009). Adjuvant radiotherapy reduced seizures at recurrence in a univariate analysis (OR 0.14, 0.03-0.7, p = 0.020). Patients with seizure freedom after surgery and AT displayed longer progression-free survival (PFS) (65, 24.5-105, vs 48 months, 32-63.5, p = 0.037). DISCUSSION: This study analyzed seizure control in patients with IDH1/2-mutant lower-grade glioma across multiple time points. Grade 3 correlated with better seizure control throughout the entire disease trajectory, and seizure freedom after surgery and AT correlated with a longer PFS regardless of tumor grade. These results could serve as an external control arm in clinical trials evaluating the efficacy on seizures of antitumor agents in patients with IDH-mutant lower-grade glioma.

Helical tomotherapy and two types of volumetric modulated arc therapy: dosimetric and clinical comparison for several cancer sites.

Radiotherapy accelerators have undergone continuous technological developments. We investigated the differences between Radixact™ and VMAT treatment plans. Sixty patients were included in this study. Dosimetric comparison between the Radixact™ and VMAT plans was performed for six cancer sites: whole-brain, head and neck, lymphoma, lung, prostate, and rectum. The VMAT plans were generated with two Elekta linear accelerators (Synergy® and Versa HD™). The planning target volume (PTV) coverage, organs-at-risk dose constraints, and four dosimetric indexes were considered. The deliverability of the plans was assessed using quality assurance (gamma index evaluation) measurements; clinical judgment was included in the assessment. The mean AAPM TG218 (3%-2 mm, global normalization) gamma index values were 99.4%, 97.8%, and 96.6% for Radixact™, Versa HD™, and Synergy®, respectively. Radixact™ performed better than Versa HD™ in terms of dosimetric indexes, hippocampi D100%, spinal cord Dmax, rectum V38.4  Gy, bladder V30 Gy, and V40 Gy. Versa HD™ saved more of the (lungs-PTV) V5 Gy and (lungs-PTV) Dmean, heart Dmean, breasts V4 Gy, and bowel V45 Gy. Regarding Synergy®, the head and neck Radixact™ plan saved more of the parotid gland, oral cavity, and supraglottic larynx. From a clinical point of view, for the head and neck, prostate, and rectal sites, the Radixact™ and Versa HD™ plans were similar; Radixact™ plans were preferable for the head and neck and rectum to Synergy® plans. The quality of linac plans has improved, and differences with tomotherapy have decreased. However, tomotherapy continues to be an essential add-on in multi-machine departments.

Modern Stereotactic Radiotherapy for Brain Metastases from Lung Cancer: Current Trends and Future Perspectives Based on Integrated Translational Approaches.

Brain metastases (BMs) represent the most frequent metastatic event in the course of lung cancer patients, occurring in approximately 50% of patients with non-small-cell lung cancer (NSCLC) and in up to 70% in patients with small-cell lung cancer (SCLC). Thus far, many advances have been made in the diagnostic and therapeutic procedures, allowing improvements in the prognosis of these patients. The modern approach relies on the integration of several factors, such as accurate histological and molecular profiling, comprehensive assessment of clinical parameters and precise definition of the extent of intracranial and extracranial disease involvement. The combination of these factors is pivotal to guide the multidisciplinary discussion and to offer the most appropriate treatment to these patients based on a personalized approach. Focal radiotherapy (RT), in all its modalities (radiosurgery (SRS), fractionated stereotactic radiotherapy (SRT), adjuvant stereotactic radiotherapy (aSRT)), is the cornerstone of BM management, either alone or in combination with surgery and systemic therapies. We review the modern therapeutic strategies available to treat lung cancer patients with brain involvement. This includes an accurate review of the different technical solutions which can be exploited to provide a "state-of-art" focal RT and also a detailed description of the systemic agents available as effective alternatives to SRS/SRT when a targetable molecular driver is present. In addition to the validated treatment options, we also discuss the future perspective for focal RT, based on emerging clinical reports (e.g., SRS for patients with many BMs from NSCLC or SRS for BMs from SCLC), together with a presentation of innovative and promising findings in translational research and the combination of novel targeted agents with SRS/SRT.

Peritransplant Radiation Therapy in Patients With Refractory or Relapsed Hodgkin Lymphoma Undergoing Autologous Stem Cell Transplant: Long-Term Results of a Retrospective Study of the Fondazione Italiana Linfomi.

PURPOSE: In this multicenter collaboration, we report real-world data in the largest published series of long-term outcomes for patients with relapsed/refractory (r/r) Hodgkin lymphoma (HL) treated with peritransplant radiation therapy (pt-RT) and high-dose chemotherapy with autologous stem cell transplant (ASCT). METHODS AND MATERIALS: We conducted a retrospective analysis including data from 12 institutions. Eligibility required histologic diagnosis of HL, receipt of ASCT plus pt-RT between 2004 and 2014 for r/r HL, and age ≥18 years at the time of ASCT. All patients received salvage chemotherapy for maximum debulking before ASCT. Metabolic responses were scored according to the Lugano Classification. The primary endpoint was overall survival (OS). Univariate and multivariate Cox proportional hazards were calculated to estimate the effect of covariates on patients' outcome. RESULTS: One hundred thirty-one patients were eligible: 68 were male (52%), and median age at ASCT was 32 years (range, 18-70). At the time of diagnosis with r/r HL, 92 patients (70%) had limited (stage I-II) disease, and 10 patients (8%) had bulky disease. Pt-RT was given pre-ASCT in 32 patients (24%) and post-ASCT in 99 (76%); median prescribed dose was 30.6 Gy (range, 20-44 Gy). With median follow-up of 60 months, 3- and 5-year OS were 84% and 77%, while 3- and 5-year progression-free survival were 75% and 72%, respectively. On univariate and multivariate analysis, advanced stage at relapse (hazard ratio [HR], 2.18; P = .04), irradiation of >3 sites (HR, 3.69; P = .01), and incomplete metabolic response after salvage chemotherapy (HR, 2.24; P = .01) had a negative effect on OS. The sequencing of pt-RT (pre- vs post-ASCT) did not affect outcomes. CONCLUSIONS: Overall, the addition of pt-RT to ASCT for patients with r/r HL is associated with very good outcomes. Limited relapsed disease with ≤3 sites involved and achievement of complete metabolic response after salvage chemotherapy were predictive of more favorable prognosis.

A Quality Control Study on Involved Node Radiation Therapy in the European Organisation for Research and Treatment of Cancer/Lymphoma Study Association/Fondazione Italiana Linfomi H10 Trial on Stages I and II Hodgkin Lymphoma: Lessons Learned.

PURPOSE: Involved node radiation therapy (INRT) was introduced in the European Organisation for Research and Treatment of Cancer/Lymphoma Study Association/Fondazione Italiana Linfomi H10 trial, a large multicenter trial in early-stage Hodgkin Lymphoma. The present study aimed to evaluate the quality of INRT in this trial. METHODS AND MATERIALS: A retrospective, descriptive study was initiated to evaluate INRT in a representative sample encompassing approximately 10% of all irradiated patients in the H10 trial. Sampling was stratified by academic group, year of treatment, size of the treatment center, and treatment arm, and it was done proportional to the size of the strata. The sample was completed for all patients with known recurrences to enable future research on relapse patterns. Radiation therapy principle, target volume delineation and coverage, and applied technique and dose were evaluated using the EORTC Radiation Therapy Quality Assurance platform. Each case was reviewed by 2 reviewers and, in case of disagreement also by an adjudicator for a consensus evaluation. RESULTS: Data were retrieved for 66 of 1294 irradiated patients (5.1%). Data collection and analysis were hampered more than anticipated by changes in archiving of diagnostic imaging and treatment planning systems during the running period of the trial. A review could be performed on 61 patients. The INRT principle was applied in 86.6%. Overall, 88.5% of cases were treated according to protocol. Unacceptable variations were predominately due to geographic misses of the target volume delineations. The rate of unacceptable variations decreased during trial recruitment. CONCLUSIONS: The principle of INRT was applied in most of the reviewed patients. Almost 90% of the evaluated patients were treated according to the protocol. The present results should, however, be interpreted with caution because the number of patients evaluated was limited. Individual case reviews should be done in a prospective fashion in future trials. Radiation therapy Quality Assurance tailored to the clinical trial objectives is strongly recommended.

Refining critical structure contouring in STereotactic Arrhythmia Radioablation (STAR): Benchmark results and consensus guidelines from the STOPSTORM.eu consortium.

BACKGROUND AND PURPOSE: In patients with recurrent ventricular tachycardia (VT), STereotactic Arrhythmia Radioablation (STAR) shows promising results. The STOPSTORM.eu consortium was established to investigate and harmonise STAR treatment in Europe. The primary goals of this benchmark study were to standardise contouring of organs at risk (OAR) for STAR, including detailed substructures of the heart, and accredit each participating centre. MATERIALS AND METHODS: Centres within the STOPSTORM.eu consortium were asked to delineate 31 OAR in three STAR cases. Delineation was reviewed by the consortium expert panel and after a dedicated workshop feedback and accreditation was provided to all participants. Further quantitative analysis was performed by calculating DICE similarity coefficients (DSC), median distance to agreement (MDA), and 95th percentile distance to agreement (HD95). RESULTS: Twenty centres participated in this study. Based on DSC, MDA and HD95, the delineations of well-known OAR in radiotherapy were similar, such as lungs (median DSC = 0.96, median MDA = 0.1 mm and median HD95 = 1.1 mm) and aorta (median DSC = 0.90, median MDA = 0.1 mm and median HD95 = 1.5 mm). Some centres did not include the gastro-oesophageal junction, leading to differences in stomach and oesophagus delineations. For cardiac substructures, such as chambers (median DSC = 0.83, median MDA = 0.2 mm and median HD95 = 0.5 mm), valves (median DSC = 0.16, median MDA = 4.6 mm and median HD95 = 16.0 mm), coronary arteries (median DSC = 0.4, median MDA = 0.7 mm and median HD95 = 8.3 mm) and the sinoatrial and atrioventricular nodes (median DSC = 0.29, median MDA = 4.4 mm and median HD95 = 11.4 mm), deviations between centres occurred more frequently. After the dedicated workshop all centres were accredited and contouring consensus guidelines for STAR were established. CONCLUSION: This STOPSTORM multi-centre critical structure contouring benchmark study showed high agreement for standard radiotherapy OAR. However, for cardiac substructures larger disagreement in contouring occurred, which may have significant impact on STAR treatment planning and dosimetry evaluation. To standardize OAR contouring, consensus guidelines for critical structure contouring in STAR were established.

Management of relapsed or refractory large B-cell lymphoma in patients ineligible for CAR-T cell therapy.

INTRODUCTION: Chimeric antigen receptor T (CAR-T) therapy has revolutionized the treatment of relapsed/refractory large B-cell lymphoma (LBCL). However, patients who are excluded or have no access to CAR-T represent a challenge for clinicians and have generally a dismal outcome. The landscape for this category of patients is constantly evolving: new agents have been approved in the last 2-3 years, alone or in combination, and novel treatment modalities are under investigation. AREAS COVERED: Thereafter, we reviewed the currently available therapeutic strategies: conventional chemotherapy, antibody-drug conjugate ADC (mainly polatuzumab and loncastuxumab), bispecific antibodies (CD19/CD3 and focus on novel CD20/CD3 Abs), immunomodulatory drugs (covering tafasitamab and lenalidomide, checkpoint inhibitors mainly in PMBL), small molecules (selinexor, BTK, and PI3K inhibitors), and the role of radiotherapy. EXPERT OPINION: Navigating this scenario will uncover new challenges, including identifying an ideal sequence for these therapies, the most effective combinations, and search for consistent predictive factors to help selecting the appropriate population of LBCL patients. At present, supporting clinical research for CAR-T ineligible patients, a new and challenging group, must remain a major focus that is complementary to advances in CAR T-cell therapy.

A case report of long-term successful stereotactic arrhythmia radioablation in a cardiac contractility modulation device carrier with giant left atrium, including a detailed dosimetric analysis.

Introduction: Catheter ablation (CA) is the current standard of care for patients suffering drug-refractory monomorphic ventricular tachycardias (MMVTs). Yet, despite significant technological improvements, recurrences remain common, leading to increased morbidity and mortality. Stereotactic arrhythmia radioablation (STAR) is increasingly being adopted to overcome the limitations of conventional CA, but its safety and efficacy are still under evaluation. Case presentation: We hereby present the case of a 73-year-old patient implanted with a mitral valve prosthesis, a cardiac resynchronization therapy-defibrillator, and a cardiac contractility modulation device, who was successfully treated with STAR for recurrent drug and CA-resistant MMVT in the setting of advanced heart failure and a giant left atrium. We report a 2-year follow-up and a detailed dosimetric analysis. Conclusion: Our case report supports the early as well as the long-term efficacy of 25 Gy single-session STAR. Despite the concomitant severe heart failure, with an overall heart minus planned target volume mean dosage below 5 Gy, no major detrimental cardiac side effects were detected. To the best of our knowledge, our dosimetric analysis is the most accurate reported so far in the setting of STAR, particularly for what concerns cardiac substructures and coronary arteries. A shared dosimetric planning among centers performing STAR will be crucial in the next future to fully disclose its safety profile.

An integrated approach to cardioprotection in lymphomas.

In potentially curable cancers, long-term survival depends not only on the successful treatment of the malignancy but also on the risks associated with treatment-related toxicity, especially cardiotoxicity. Malignant lymphomas affect patients at any age, with acute and late toxicity risks that could have a severe effect on morbidity, mortality, and quality of life. Although our understanding of chemotherapy-associated and radiotherapy-associated cardiovascular disease has advanced considerably, new drugs with potential cardiotoxicity have been introduced for the treatment of lymphomas. In this Review, we summarise the mechanisms of treatment-related cardiac injury, available clinical data, and protocols for optimising cardioprotection in lymphomas. We discuss ongoing research strategies to advance our knowledge of the molecular basis of drug-induced and radiation-induced toxicity. Additionally, we emphasise the potential for personalised follow-up and early detection, including the role of biomarkers and novel diagnostic tests, highlighting the role of the cardio-oncology team.

Role of Radiosurgery and Stereotactic Ablative Radiotherapy for Oligometastatic Non-Oncogene Addicted NSCLC.

Local ablative therapy (LAT), intended as stereotactic ablative radiotherapy or stereotactic radiosurgery, is a well-recognized effective treatment for selected patients with oligometastatic NSCLC. Current clinical evidence supports LAT alone or in combination with systemic therapies. Our retrospective mono-institutional study aims to assess the role of LAT with a peculiar focus on the largest series of non-oncogene addicted oligometastatic NSCLC patients to date. We included in this analysis all patients with the mentioned disease characteristics who underwent LAT for intracranial and/or extracranial metastases between 2011 and 2020. The main endpoints were local control (LC), progression free survival (PFS) and overall survival (OS) in the whole population and after stratification for prognostic factors. We identified a series of 245 consecutive patients (314 lesions), included in this analysis (median age 69 years). In 77% of patients, a single metastasis was treated with LAT and intracranial involvement was the most frequent indication (53% of patients) in our series. The overall response rate (ORR) after LAT was 95%. In case of disease progression, 66 patients underwent new local treatments with curative intent. With a median follow-up of 18 months, median PFS was 13 months (1-year PFS 50%) and median OS was 32 months (1-year OS 75%). The median LC was not reached (1-year LC 89%). The presence of brain metastases was the only factor that negatively affected all clinical endpoints, with a 1-year LC, PFS and OS of 82%, 29% and 62% respectively, compared to 95%, 73% and 91%, respectively, for patients without BMs (p < 0.001 for each endpoint). At the multivariate analysis, mediastinal nodal involvement at baseline (p = 0.049), ECOG PS = 1 (p = 0.011), intracranial disease involvement (p = 0.001), administration of chemotherapy in combination with LAT (p = 0.020), and no delivery of further local treatment for progression or delivery of focal treatment for intracranial progression (p < 0.001) were related to a poorer OS. In our retrospective series, which is to our knowledge the largest to date, LAT showed encouraging results and confirmed the safety and effectiveness of focal treatments in non-oncogene addicted oligometastatic NSCLC patients.

Impact of contrast-induced acute kidney injury definition on clinical outcomes.

BACKGROUND: Contrast-induced acute kidney injury (CIAKI) is a frequent complication after infusion of contrast media in patients undergoing percutaneous coronary intervention. A wide range of CIAKI rates occurs after intervention between 3% and 30%, depending on the definition. The aim of this study was to identify which methodology was more effective at recognizing patients at high risk for in-hospital and out-of-hospital adverse events. METHODS AND RESULTS: Serum creatinine increases, after contrast agent infusion, were evaluated in 755 consecutive and unselected patients. Incidences of CIAKI diagnosed by 2 common definitions varied from 6.9% (creatinine increase of ≥0.5 mg/dL, CIAKI-0.5) to 15.9% (creatinine increase of ≥25%, CIAKI-25%). Significant differences appeared between the 2 definitions of sensitivity to predict renal failure according to receiver operating characteristic curve analysis (98% for CIAKI-0.5 and 62% for CIAKI-25%), using a cutoff value of postprocedural glomerular filtration rate of 60 mL/min. Both definitions of CIAKI were related to composite adverse events, but CIAKI-0.5 showed a stronger predicting value (odds ratio 2.875 vs 1.802, P = .036). In multivariate linear regression, only CIAKI-0.5 was a predictive variable of death (odds ratio 3.174, 95% CI 1.368-7.361). CONCLUSIONS: An increase in serum creatinine of ≥0.5 mg/dL is more sensitive because it recognizes more selectively those patients with a higher risk of mortality and morbidity. Serum creatinine increases of ≥25% overestimate CIAKI by including many patients without postprocedural relevant deterioration of renal function and affected by a lower risk of adverse events at follow-up.

The role of motion management and position verification in lymphoma radiotherapy.

In the last decades, the substantial technical progress in radiation oncology offered the opportunity for more accurate planning and delivery of treatment. At the same time, the evolution of systemic treatment and the advent of modern diagnostic tools allowed for more accurate staging and consequently a safe reduction of radiotherapy (RT) target volumes and RT doses in the treatment of lymphomas. As a result, incidental irradiation of organs at risk was reduced, with a consequent reduction of severe late toxicity in long-term lymphoma survivors. Nevertheless, these innovations warrant that professionals pay attention to concurrently ensure precise planning and dose delivery to the target volume and safe sparing of the organs at risk. In particular, target and organ motion should be carefully managed in order to prevent any compromise of treatment efficacy. Several aspects should be taken into account during the treatment pathway to minimise uncertainties and to apply a valuable motion management strategy, when needed. These include: reliable image registration between diagnostic and planning radiologic exams to facilitate the contouring process, image guidance to limit positioning uncertainties and to ensure the accuracy of dose delivery and management of lung motion through procedures of respiratory gating and breath control. In this review, we will cover the current clinical approaches to minimise these uncertainties in patients treated with modern RT techniques, with a particular focus on mediastinal lymphoma. In addition, since uncertainties have a different impact on the dose deposition of protons compared to conventional x-rays, the role of motion management and position verification in proton beam therapy (PBT) will be discussed in a separate section.