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The prospective, multicentric phase II GAZAI study of the German Lymphoma Alliance (GLA) investigated the efficacy of low dose radiation therapy (2 × 2 Gy) in combination with the anti-CD20 antibody Obinutuzumab in early stage nodal FL. At week 18, metabolic CR (Deauville score (DS) <3) was seen in 46/53 patients (87%; one patient only had a CT without FDG-PET). B Introduction: b The FORT trial demonstrated a higher complete remission (CR) rate using 12 × 2 Gy compared to 2 × 2 Gy in Follicular Lymphoma (FL) (67% vs. 47%). [Extracted from the article]

Purpose: To prospectively investigate the role of re-irradiation (re-RT) combined with hyperthermia (HT) in a contemporary cohort of patients affected by recurrent breast cancer (RBC).Methods: Within the prospective registry HT03, patients with resected RBC and previous irradiation were included. Re-RT was applied to the recurrence region with doses of 50-50.4 Gy, with a boost up to 60-60.4 Gy to the microscopically or macroscopically positive resection margins (R1/R2) region. Concurrent HT was performed at 40-42 ℃. Primary endpoint was LC. Acute and late toxicity, overall survival, cancer-specific survival (CSS), and progression-free survival (PFS) were also evaluated.Results: 20 patients and 21 RBC were analyzed. Median re-RT dose was 50.4 Gy and a median of 11 HT fractions were applied. Re-RT+HT was well tolerated, with three patients who experienced a grade (G) 3 acute skin toxicity and no cases of ≥G3 late toxicity. With a median follow up of 24.7 months, two local relapses occurred. Ten patients experienced regional and/or distant disease progression. Five patients died, four of them from breast cancer. PFS was favorable in patients treated with re-RT+HT for the first recurrence with doses of 60 Gy. A trend towards better CSS was found in patients with negative or close margins and after doses of 60 Gy.Conclusion: Full-dose re-RT+HT for RBC is well tolerated, provides good LC, and seems to be more effective when applied at the time of the first relapse and after doses of 60 Gy. The registry will be continued for validation in a larger cohort and with longer follow-up. [ABSTRACT FROM AUTHOR]

Background: Severe aortic stenosis (AS) is associated with left ventricular (LV) remodelling, likely causing alterations in coronary blood flow and microvascular resistance., Aims: We aimed to evaluate changes in absolute coronary flow and microvascular resistance in patients with AS undergoing transcatheter aortic valve implantation (TAVI)., Methods: Consecutive patients with AS undergoing TAVI with non-obstructive coronary artery disease in the left anterior descending artery (LAD) were included. Absolute coronary flow (Q) and microvascular resistance (R μ ) were measured in the LAD using continuous intracoronary thermodilution at rest and during hyperaemia before and after TAVI, and at 6-month follow-up. Total myocardial mass and LAD-specific mass were quantified by echocardiography and cardiac computed tomography. Regional myocardial perfusion (Q N ) was calculated by dividing absolute flow by the subtended myocardial mass., Results: In 51 patients, Q and R were measured at rest and during hyperaemia before and after TAVI; in 20 (39%) patients, measurements were also obtained 6 months after TAVI. No changes occurred in resting and hyperaemic flow and resistance before and after TAVI nor after 6 months. However, at 6-month follow-up, a notable reverse LV remodelling resulted in a significant increase in hyperaemic perfusion (Q N,hyper : 0.86 [interquartile range {IQR} 0.691.06] vs 1.20 [IQR 0.99-1.32] mL/min/g; p=0.008; pre-TAVI and follow-up, respectively) but not in resting perfusion (Q N,rest : 0.34 [IQR 0.30-0.48] vs 0.47 [IQR 0.36-0.67] mL/min/g; p=0.06)., Conclusions: Immediately after TAVI, no changes occurred in absolute coronary flow or coronary flow reserve. Over time, the remodelling of the left ventricle is associated with increased hyperaemic perfusion.

Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is a rare hematologic malignancy that can manifest with skin nodules and erythematous plaques. In most cases BPDCN progresses rapidly, causing multiple skin lesions and also affecting internal organs and bone marrow, warranting initiation of systemic therapies or hematopoietic stem cell transplantation (HCT). Although not curative, radiotherapy for isolated lesions might be indicated in case of (imminent) ulceration and large or symptomatic lesions. To this end, doses of 27.0-51.0 Gy have been reported. Here, we present the case of an 80-year-old male with BPDCN with multiple large, nodular, and ulcerating lesions of the thorax, abdomen, and face. Low-dose radiotherapy of 2 × 4.0 Gy was administered to several lesions, which resolved completely within 1 week with only light residual hyperpigmentation of the skin in affected areas and reliably prevented further ulceration. Radiotoxicity was not reported. Therefore, low-dose radiotherapy can be an effective and low-key treatment in selected cases of BPDCN, especially in a palliative setting, with a favorable toxicity profile., (© 2024. The Author(s).)

Ever since its introduction as a diagnostic imaging tool the potential of magnetic resonance imaging (MRI) in radiation therapy (RT) treatment simulation and planning has been recognized. Recent technical advances have addressed many of the impediments to use of this technology and as a result have resulted in rapid and growing adoption of MRI in RT. The purpose of this article is to provide a broad review of the multiple uses of MR in the RT treatment simulation and planning process, identify several of the most used clinical scenarios in which MR is integral to the simulation and planning process, highlight existing limitations and provide multiple unmet needs thereby highlighting opportunities for the diagnostic MR imaging community to contribute and collaborate with our oncology colleagues. EVIDENCE LEVEL: 5 TECHNICAL EFFICACY: Stage 5., (© 2024 International Society for Magnetic Resonance in Medicine.)

Background: Stereotactic radiosurgery/radiotherapy (SRS/SRT) and novel systemic treatments, such as tyrosine kinase inhibitors (TKIs) and immune checkpoint inhibitors (ICIs), have demonstrated to be effective in managing brain metastases in non-small cell lung cancer (NSCLC). However, the optimal treatment sequence of SRS/SRT and TKI/ICI remains uncertain. This retrospective monocentric analysis addresses this question by comparing the outcomes of patients with NSCLC brain metastases who received upfront SRS/SRT versus those who were initially treated with TKI/ICI., Methods: All patients treated with SRS/SRT and TKI/ICI for NSCLC brain metastases were collected from a clinical database. The patients who received first-line TKI or ICI for the treatment of brain metastases were then selected for further analysis. Within this cohort, a comparative analysis between upfront SRS/SRT and patients initially treated with TKI/ICI was conducted, assessing key parameters such as overall survival (OS), intracranial progression-free survival (iPFS) and treatment-related toxicity. Both OS and iPFS were defined as the time from SRS/SRT to either death or disease progression, respectively., Results: The analysis encompassed 54 patients, of which 34 (63.0%) patients received SRS/SRT and TKI/ICI as their first-line therapy. Of the latter, 17 (50.0%) patients received upfront SRS/SRT and 17 (50.0%) were initially treated with TKI/ICI; 24 (70.6%) received SRS/SRT and ICI, and 10 (29.4%) received SRS/SRT and TKI. The cohorts did not significantly differ in the univariable analyses for the following parameters: sex, age, histology, molecular genetics, disease stage at study treatment, performance status, number of brain metastases, treatment technique, tumor volume, target volume, disease progression, radiation necrosis, dosimetry. While no significant differences were found in terms of iPFS and OS between patients treated with upfront SRS/SRT and patients initially treated with TKI, upfront SRS/SRT demonstrated significantly superior OS when compared to patients initially treated with ICI (median OS not reached vs. 17.5 months; mean 37.8 vs. 23.6 months; P=0.03) with no difference in iPFS. No significant differences in treatment-related toxicity were observed among the cohorts., Conclusions: In this retrospective, single-center cohort study, patients treated with upfront SRS/SRT demonstrated significantly longer OS compared to patients initially treated with ICI in the cohort receiving first-line therapy for brain metastases. However, given the retrospective design and the limited cohort size, definitive conclusions cannot be drawn from these findings. Nevertheless, the results suggest that the timing of SRS/SRT may play an important role in treatment outcomes. Further investigation, preferably through prospective randomized trials, is warranted to provide more conclusive answers to this important question., Competing Interests: Conflicts of Interest: All authors have completed the ICMJE uniform disclosure form (available at https://tlcr.amegroups.com/article/view/10.21037/tlcr-24-132/coif). R.B. received Open Access Fund from University of Tübingen, and received honoraria from NovoCure for participating in invited meetings of specialized centers. C.B. received grants or contracts not related to this manuscript from Viewray, Brainlab and Elekta, and received support for attending meetings and/or travel from BMS, Roche, Merck, AstraZeneca and Viewray. F.M. received an unrestricted Research Institutional Grant from AstraZeneca, received honoraria from AstraZeneca, Novartis, Roche, Lilly, Elekta and Brainlab, and serves in the advisory board of AstraZeneca and Novartis. M.N. received payments from Brainlab and AstraZeneca for speaking services. The other authors have no conflicts of interest to declare., (2024 Translational Lung Cancer Research. All rights reserved.)

Background: To identify anatomical and morphological plaque features predictors of PCI and create a multiparametric score to increase the predictive yield. Moreover, we assessed the incremental predictive value of FFR CT (Fractional Flow Reserve derived from CCTA) trans-lesion gradient (ΔFFR CT ) when integrated into the score., Methods: Observational cohort study including patients undergoing CCTA for suspected coronary artery disease, with FFR CT available, referred to invasive coronary angiogram and assessment of fractional flow reserve. Plaque analysis was performed using validated semi-automated software. Logistic regression was performed to identify anatomical and morphological plaque features predictive of PCI. Optimal thresholds were defined by area under the receiver-operating characteristics curve (AUC) analysis. A scoring system was developed in a derivation cohort (70 ​% of the study population) and tested in a validation cohort (30 ​% of patients)., Results: The overall study population included 340 patients (455 vessels), among which 238 patients (320 vessels) were included in the derivation cohort. At multivariate logistic regression analysis, absence of left main disease, diameter stenosis (DS), non-calcified plaque (NCP) volume, and percent atheroma volume (PAV) were independent predictors of PCI. Optimal thresholds were: DS ​≥ ​50 ​%, volume of NCP>113 ​mm 3 and PAV>17 ​%. A weighted score (CT-PCI Score) ranging from 0 to 11 was obtained. The AUC of the score was 0.80 (95%CI 0.74-0.86). The integration of ΔFFR CT in the CT-PCI score led to a mild albeit not significant increase in the AUC (0.82, 95%CI 0.77-0.87, p ​= ​0.328)., Conclusions: Plaque anatomy and morphology derived from CCTA could aid in identifying patients amenable to PCI., Competing Interests: Declaration of competing interest MB, PP, DTB, AL and MMV report research grants provided by Cardiopath Ph.D. program. NM has received speaker fees from Abbott. CC reports receiving research grants from Biosensor, Coroventis Research, Medis Medical Imaging, Pie Medical Imaging, Cathworks, Boston Scientific, Siemens, HeartFlow Inc., and Abbott Vascular; and consultancy fees from Heart Flow Inc, Opsens, Abbott Vascular, and Philips Volcano. BDB reports receiving consultancy fees from Boston Scientific, and Abbott and receiving research grants from Coroventis Research, Pie Medical Imaging, Cathworks, Boston Scientific, Siemens, HeartFlow Inc., and Abbott Vascular. DA reports research grants from GE Healthcare and Bracco. The other authors have nothing to disclose., (Copyright © 2024 Society of Cardiovascular Computed Tomography. Published by Elsevier Inc. All rights reserved.)

Background: Coronary microvascular dysfunction (CMD) is involved in heart failure (HF) onset and progression, independently of HF phenotype and obstructive coronary artery disease. Invasive assessment of CMD might provide insights into phenotyping and prognosis of patients with HF. We aimed to assess absolute coronary flow, absolute microvascular resistance, myocardial perfusion, coronary flow reserve, and microvascular resistance reserve in patients with HF with preserved ejection fraction and HF with reduced ejection fraction (HFrEF)., Methods: Single-center, prospective study of 56 consecutive patients with de novo HF with nonobstructive coronary artery disease divided into HF with preserved ejection fraction (n=21) and HFrEF (n=35). CMD was invasively assessed by continuous intracoronary thermodilution and defined as coronary flow reserve <2.5. Left ventricular and left anterior descending artery-related myocardial mass was quantified by echocardiography and coronary computed tomography angiography. Myocardial perfusion (mL/min per g) was calculated as the ratio between absolute coronary flow and left anterior descending artery-related mass., Results: Patients with HFrEF showed a higher left ventricular and left anterior descending artery-related myocardial mass compared with HF with preserved ejection fraction ( P <0.010). Overall, 52% of the study population had CMD, with a similar prevalence between the 2 groups. In HFrEF, CMD was characterized by lower absolute microvascular resistance and higher absolute coronary flow at rest (functional CMD; P =0.002). CMD was an independent predictor of a lower rate of left ventricular reverse remodeling at follow-up. In patients with HF with preserved ejection fraction, CMD was mainly due to higher absolute microvascular resistance and lower absolute coronary flow during hyperemia (structural CMD; P ≤0.030)., Conclusions: Continuous intracoronary thermodilution allows the definition and characterization of patterns with distinct CMD in patients with HF and could identify patients with HFrEF with a higher rate of left ventricular reverse remodeling at follow-up., Competing Interests: Disclosures Drs Paolisso, Belmonte, Bertolone, Leone, Esposito, Fabbricatore, and Moya were supported by a research grant from the CardioPaTh PhD Program. Dr De Bruyne has a consulting relationship with Boston Scientific, Abbott Vascular, CathWorks, Siemens, and Coroventis Research; receives research grants from Abbott Vascular, Coroventis Research, CathWorks, and Boston Scientific; and holds minor equities in Philips Volcano, Siemens, GE Healthcare, Edwards Life Sciences, HeartFlow, Opsens, and Celiad. Dr Barbato declares speaker’s fees from Abbott Vascular, Boston Scientific, and GE Healthcare. Dr Bartunek reports consultancy fees from Occlutech, unrelated to the topic of the manuscript. The other authors report no conflicts.

Acute decompensated heart failure (ADHF) is a major cause of hospitalizations in older adults, leading to high mortality, morbidity, and healthcare costs. To address the persistent poor outcomes in ADHF, novel device-based approaches targeting specific pathophysiological mechanisms are urgently needed. The recently introduced DRI 2 P 2 S classification categorizes these innovative therapies based on their mechanisms. Devices include dilators (increasing venous capacitance), removers (directly removing sodium and water), inotropes (enhancing left ventricular contractility), interstitials (accelerating lymph removal), pushers (increasing renal arterial pressure), pullers (decreasing renal venous pressure), and selective drippers (selective intrarenal drug infusion). Some are tailored for chronic HF, while others focus on the acute setting. Most devices are in early development, necessitating further research to understand mechanisms, assess clinical effectiveness, and ensure safety before routine use in ADHF management. Exploring these innovative device-based strategies may lead to improved outcomes and revolutionize HF treatment in the future., Competing Interests: Declaration of Competing Interest DTB, PP, MB, GE, DF, CV, AL and MMV are supported by a research grant from the CardioPaTh PhD Program. The remaining authors have nothing to declare., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Competing Interests: Funding Support and Author Disclosures Drs Belmonte, Paolisso, Viscusi, and Bertolone have received a research grant from the CardioPaTh PhD Program. Mr Danino and Dr Planer are founders of Innoventric. Mr Pichersky, Ms Lereya, and Mr Kislev are employees of Innoventric. Dr Bartunek reports consultancy fees from Occlutech, unrelated to the topic of the manuscript. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose.

Objective: To assess aortic regurgitation (AR) prevalence, its hemodynamic effect, and long-term prognostic implications in patients admitted with de novo or worsened heart failure with preserved ejection fraction (HFpEF)., Methods: Consecutive patients hospitalized with de novo or worsened HFpEF between 2014 and 2020 were enrolled. Patients with more than moderate aortic and/or mitral valve disease were excluded. Based on the presence and degree of AR, patients were divided into those without AR, those with mild, and those with moderate AR. Data on cardiovascular death, heart failure (HF) rehospitalization, and their composite (major adverse cardiovascular events) were collected., Results: The final study population consisted of 458 HFpEF patients: 156 (34.1%) with mild-AR, 153 (33.4%) with moderate-AR, and the remaining 149 (32.5%) with no AR. Mild-to-moderate AR patients were older, with larger left atrium-left ventricle (LV) volumes, greater LV mass index, higher filling pressure, and prevalence of diastolic dysfunction compared with the no-AR group (all P<.05). During 5-year follow-up, 113 patients died of cardiovascular causes, 124 patients were rehospitalized for HF, whereas 196 experienced the composite endpoint. Mild-to-moderate AR was identified as an independent predictor of all-cause death (HR, 1.62; 95% CI, 1.14 to 1.58; P=.04) and major adverse cardiovascular event occurrence (HR, 1.48; 95% CI, 1.05 to 2.09; P=.02). A total of 126 (35.5%) of 355 patients showed progression of AR at follow-up echocardiography., Conclusion: Mild-to-moderate AR is common among patients hospitalized for HFpEF. It is associated with adverse LV remodeling and worse long-term outcomes. These findings warrant further prospective studies addressing the importance of AR in prognostic stratification and exploring therapeutic strategies to mitigate its hemodynamic effect on HF., (Copyright © 2023. Published by Elsevier Inc.)