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Smooth muscle neoplasms are more frequent in human immunodeficiency infected children than in HIV seropositive adults. Endobronchial leiomyoma is a rare benign tumor in HIV infected adult patients. Epstein-Barr virus (EBV) has been implicated in the pathogenesis of these tumors. Here we describe an adult patient with HIV infection with atelectasis of the left upper pulmonary lobe as the first clinical expression of an intrabronchial leiomyoma. In this case, we can not show the association with EBV. Our report suggests that smooth muscle tumors as leiomyoma should be included in the differential diagnosis of endobronchial masses in AIDS patients.Neoplasmas da musculatura lisa são mais freqüentes em crianças infectadas pelo vírus da imunodeficiência humana do que em adultos HIV-soropositivos. Leiomioma endobronquial é um tumor benigno em pacientes adultos infectados por HIV. Vírus Epstein-Barr (EBV) tem sido implicado na patogenia destes tumores. Descrevemos paciente adulto infectado pelo HIV com atelectasia do lobo pulmonar superior esquerdo como primeira manifestação clínica de leiomioma intrabronquial. Neste caso não pudemos demonstrar a associação com EBV. Nosso relato sugere que tumores de musculatura lisa como leiomioma deveriam ser incluídos no diagnóstico diferencial de massas endobronquiais em pacientes com AIDS.

The aim of this study was to present a nationwide survey on the specialist's attitudes towards stereotactic body radiotherapy (SBRT) combined with poly (ADP-ribose) polymerase inhibitors (PARPi) with oligometastatic/oligoprogressive/oligorecurrent ovarian cancer (oMPR-OC) patients. The 19-item questionnaire was developed by specialists and distributed online. Replies were stratified by categories and analyzed using descriptive statistics. Respondents ( N = 100) were radiation oncologists (57%), medical oncologists (32%), and gynecologic oncologists (11%). Fifty-four percent of respondents considered medical oncologists as the primary oncologists for oMPR-OC, while 23% preferred radiation oncologists and 15% favored gynecologic oncologists. Seventy-three percent discuss these cases in the Multidisciplinary Tumor Board, while 15, 6, and 2% send the patients straight to SBRT, surgery, or chemotherapy, respectively. Seventy-four percent of the experts interviewed were treated with SBRT less than 10 oMPR-OC patients. Concomitant treatment was highly heterogeneous, but it had little to no reported side effects. A significant variation in how PARPi is managed during SBRT was found: 34% do not interrupt the administration, while 52% pause and restart it later. Forty-three percent of respondents believe that the PARPi dosage should not be reduced when administered concurrently with SBRT. Sixty-nine percent of respondents believe that the SBRT dose should not be decreased while receiving PARPi if the constraints are met. The majority of respondents (40%) favored expert consensus for enhancing the clinical management of oMPR-OC, while 34% preferred clinical guidelines. A lack of or low toxicity with the combination of PARPi and SBRT was perceived, and a significant degree of heterogeneity concerning clinical protocols for their combination. Moreover, it emphasizes the low number of patients who have received this treatment approach nationwide., (Copyright © 2025 Wolters Kluwer Health, Inc. All rights reserved.)

Purpose: MITO-RT3/RAD (NCT04593381) is a prospective multicenter phase 2 trial designed to assess the effectiveness and safety of stereotactic body radiation therapy (SBRT) in patients who received diagnoses of oligometastatic ovarian cancer. In this report, we provide the results of the trial in the setting of lymph node disease., Methods and Materials: The primary endpoint was the complete response (CR) rate, secondary endpoints included local control (LC), progression-free survival (PFS), overall survival, treatment-free interval, and toxicity rates. The sample size was based on a previous study reporting an average 70.0% CR with SBRT. The study was powered to detect an improvement in the CR rate from 70.0% to 85.0%, with an α error of 0.05 (one-side) and a β error of 0.1., Results: The study met its primary endpoint of a statistically significant improvement in CR. One hundred thirty-five patients with 249 lesions were enrolled across 15 institutions from May 2019 to November 2023. CRs were observed in 194 lesions (77.9%), partial responses in 40 (16.1%), stable disease in 14 (5.6%), and progressive disease in 1 lesion (0.4%). The objective response rate was 94%, with an overall clinical benefit rate of 99.6%. CR lesions exhibited a significantly higher LC rate than partial or not responding lesions (12-month LC: 92.7% vs 63.1%, P < .001). The 12-month actuarial rates for PFS and for overall survival were 36.6% (CR, 38.3% vs not-CR, 18.8%; P, .022) and 97.2% (CR, 97.8% vs not-CR, 93.8%; P, .067), respectively. The 12-month actuarial rate for treatment-free interval was 52.7% (CR, 58.4% vs not-CR, 24.4%; P, .004). CR was substantially associated with higher PFS (P, .036) and treatment-free interval (P, .006) rates in the univariate analysis. Twenty-three patients (17.0%) experienced mild acute toxicity. Late toxicity was reported in 9 patients (6.7%), mostly grade 1., Conclusions: This trial confirms the efficacy of ablative SBRT, with minimal toxicity observed. SBRT offered a high CR rate, promising long-term outcomes, and a significant systemic therapy-free survival period for complete responders., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The utilization of poly-ADP-ribose polymerase (PARP) inhibitors (PARPi) as a first-line maintenance therapy for advanced ovarian cancer has increased significantly, with ∼80% of patients potentially eligible. This expansion has led to a rise in the population experiencing platinum-sensitive recurrence, yet data on first recurrence during PARPi are limited. This real-world study from a high-volume referral center aims to elucidate recurrence rates, disease distribution, and treatment modalities at the time of progression in PARPi-treated patients., Materials and Methods: We analyzed our prospectively maintained database to identify patients receiving first-line PARPi maintenance from January 2019 to December 2022 at our institution., Results: A total of 373 cases were identified, 51.5% of which had a BRCA mutation. With a median follow-up of 38 months, 44.8% of patients experienced recurrence, with 90.3% having a platinum-free interval exceeding 6 months. Recurrences were oligometastatic in 44.9% of cases, with BRCA mutations strongly predicting this pattern (hazard ratio 3.014, confidence interval 1.486-6.113, P = 0.002). The median progression-free survival was 39 months, significantly longer for BRCA-mutated and homologous recombination deficiency-positive patients. Over one-third of platinum-sensitive recurrent patients were candidates for local treatments, and PARPi administration was prolonged in 53.7%., Conclusions: Despite the notable survival improvement, a significant proportion of the population will experience a platinum-sensitive recurrence on PARPi, for which local treatments are often a viable option. Our study highlights the need for further research to determine whether the ablation of oligometastatic sites has a significant impact on post-recurrence survival and to identify if there are patient categories that would benefit from personalized follow-up due to their susceptibility to oligometastatic recurrences and local treatments., (Copyright © 2025 The Authors. Published by Elsevier Ltd.. All rights reserved.)

Purpose: The aim of this observational, retrospective, multicenter study (Epimetheo) was to analyze the activity and the safety of stereotactic body radiation therapy (SBRT) during poly(ADP-ribose)-polymerase inhibitor (PARPi) maintenance in a series of oligometastatic ovarian cancer (OC) patients., Methods and Materials: Patients treated with PARPi in maintenance setting received SBRT if oligometastatic progression occurred. Maintenance treatment was continued until the extensive progression of the disease. The primary endpoints of the study were as follows: next systemic treatment change-free survival (NEST-FS) and acute and late toxicity; the secondary endpoints were as follows: the rate of clinical complete response (CR), the 2-year actuarial local control (LC, progression of disease inside SBRT field) rate on "per lesion" basis, the 2-year actuarial progression-free survival, and 2-year overall survival (OS)., Results: From April 2018 to September 2023, SBRT was used to treat 74 OC patients with a total of 158 lesions (98 lymph nodes and 60 parenchymal lesions) under PARPi maintenance. Olaparib, niraparib, and rucaparib were administered to 41.9%, 48.6%, and 9.5% of patients, respectively. CR, partial response, stable disease, and progressive disease were observed in 115 (72.8%), 32 (20.3%), 9 (5.7%), and 2 lesions (1.3%), respectively. Severe toxicities were reported in less than 3% of patients. The actuarial median NEST-FS was 10 months, with a range of 6.7-13.3 months. The 12- and 24-month actuarial NEST-FS rates were 44.9% and 31.4%, respectively. The 2-year actuarial LC, progression-free survival, and OS were 68.1%, 22.5%, and 77%, respectively with differences in figures between complete and incomplete responders. The achievement of CR was found to be correlated with an improvement in LC and OS., Conclusions: This study reports the activity and the low toxicity profile of SBRT in association with PARPi in oligometastatic OC patients. A rapid, minimally invasive, and cost-effective treatment such as SBRT may be proposed as a means of prolonging NEST-FS and maintaining an effective treatment regimen involving PARPi., (Copyright © 2024 Elsevier Inc. All rights reserved.)

The risk of developing type 2 diabetes (T2D) is heterogeneous among individuals with obesity. Functional decline of adipocyte precursor cells (APCs) and accumulation of senescent cells in the subcutaneous adipose tissue contributes to the progression toward T2D. LncRNAs regulate cell senescence and may be implicated in determining this abnormality in APCs. Here, we report that APCs from individuals with obesity show a gradual increase in multiple senescence markers, which worsens in parallel with the progression from normal glucose tolerance (NGT) to impaired glucose tolerance (IGT) or T2D. Transcriptomic analysis identified PANDAR as the top-ranked lncRNA differentially expressed in APCs from individuals with obesity and T2D and non-obese subjects. Q-PCR confirmed PANDAR up-regulation in APCs from individuals with obesity, at progressively increased levels in those who developed, respectively, IGT and T2D. Bisulfite sequencing and luciferase assays revealed that, in parallel with glucose tolerance deterioration, the -1317 CpG at the PANDAR promoter became hypo-methylated in obesity, resulting in enhanced PANDAR induction by p53. PANDAR silencing in senescent APCs from individuals with obesity and T2D caused repression of senescence programs and cell cycle re-entry. PANDAR transcription in white blood cells (WBCs) mirrored that in APCs. Also, individuals with obesity exhibited rescue of PANDAR transcription in WBCs following bariatric surgery, accompanied by enhanced methylation at the regulatory PANDAR -1317 CpG. In conclusion, PANDAR dysregulation is a newly identified mechanism determining the early senescence of APCs from individuals with obesity, which worsens along the progression toward T2D. In the future, PANDAR targeting may represent a valuable strategy to delay this progression., (© 2024 The Author(s). The FASEB Journal published by Wiley Periodicals LLC on behalf of Federation of American Societies for Experimental Biology.)

Multi-modal therapies for gynecological cancers management may determine a wide range of side effects which depend on therapy-related factors and patient characteristics and comorbidities. Curative or adjuvant pelvic radiotherapy is linked with acute and late toxicity due to irradiation of organs at risk, as small and large bowel, rectum, bladder, pelvic bone, vagina and bone marrow. Successful toxicity management varies with its severity, Radiation Centre practice and experience and skills of radiation oncologists. This position paper was designed by the Italian Association of Radiation and Clinical Oncology Gynecology Study Group to provide radiation oncologists with evidence-based strategies to prevent and manage acute and late toxicities and follow-up recommendations for gynecological cancer patients submitted radiotherapy. Six workgroups of radiation oncologists with over 5 years of experience in gynecologic cancers were setup to investigate radiotherapy-related toxicities. For each topic, PubMed database was searched for relevant English language papers from January 2005 to December 2022. Titles and abstracts of results were checked to verify suitability for the document. Reference lists of selected studies and review papers were added if pertinent. Data on incidence, etiopathogenesis, prevention, treatment and follow-up of acute and late side effects for each organ at risk are presented and discussed., (© 2024. The Author(s).)

Background: Cardiovascular diseases (CVD) affect over half a billion people worldwide and are the leading cause of global deaths. In particular, due to population aging and worldwide spreading of risk factors, the prevalence of heart failure (HF) is also increasing. HF accounts for approximately 36% of all CVD-related deaths and stands as the foremost cause of hospitalization. Patients affected by CVD or HF experience a substantial decrease in health-related quality of life compared to healthy subjects or affected by other diffused chronic diseases., Main Body: For both CVD and HF, prediction models have been developed, which utilize patient data, routine laboratory and further diagnostic tests. While some of these scores are currently used in clinical practice, there still is a need for innovative approaches to optimize CVD and HF prediction and to reduce the impact of these conditions on the global population. Epigenetic biomarkers, particularly DNA methylation (DNAm) changes, offer valuable insight for predicting risk, disease diagnosis and prognosis, and for monitoring treatment. The present work reviews current information relating DNAm, CVD and HF and discusses the use of DNAm in improving clinical risk prediction of CVD and HF as well as that of DNAm age as a proxy for cardiac aging., Conclusion: DNAm biomarkers offer a valuable contribution to improving the accuracy of CV risk models. Many CpG sites have been adopted to develop specific prediction scores for CVD and HF with similar or enhanced performance on the top of existing risk measures. In the near future, integrating data from DNA methylome and other sources and advancements in new machine learning algorithms will help develop more precise and personalized risk prediction methods for CVD and HF., (© 2024. The Author(s).)

Purpose: We present a large real-world multicentric dataset of ovarian, uterine and cervical oligometastatic lesions treated with SBRT exploring efficacy and clinical outcomes. In addition, an exploratory machine learning analysis was performed., Methods: A pooled analysis of gynecological oligometastases in terms of efficacy and clinical outcomes as well an exploratory machine learning model to predict the CR to SBRT were carried out. The CR rate following radiotherapy (RT) was the study main endpoint. The secondary endpoints included the 2-year actuarial LC, DMFS, PFS, and OS., Results: 501 patients from 21 radiation oncology institutions with 846 gynecological metastases were analyzed, mainly ovarian (53.1%) and uterine metastases(32.1%).Multiple fraction radiotherapy was used in 762 metastases(90.1%).The most frequent schedule was 24 Gy in 3 fractions(13.4%). CR was observed in 538(63.7%) lesions. The Machine learning analysis showed a poor ability to find covariates strong enough to predict CR in the whole series. Analyzing them separately, in uterine cancer, if RT dose≥78.3Gy, the CR probability was 75.4%; if volume was <13.7 cc, the CR probability became 85.1%. In ovarian cancer, if the lesion was a lymph node, the CR probability was 71.4%; if volume was <17 cc, the CR probability rose to 78.4%. No covariate predicted the CR for cervical lesions. The overall 2-year actuarial LC was 79.2%, however it was 91.5% for CR and 52.5% for not CR lesions(p < 0.001). The overall 2-year DMFS, PFS and OS rate were 27.3%, 24.8% and 71.0%, with significant differences between CR and not CR., Conclusions: CR was substantially associated to patient outcomes in our series of gynecological cancer oligometastatic lesions. The ability to predict a CR through artificial intelligence could also drive treatment choices in the context of personalized oncology., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: Oligo-progression or further recurrence is an open issue in the multi-integrated management of oligometastatic disease (OMD). Re-irradiation with stereotactic body radiotherapy (re-SBRT) technique could represent a valuable treatment option to improve OMD clinical outcomes. MRI-guided allows real-time visualization of the target volumes and online adaptive radiotherapy (oART). The aim of this retrospective study is to evaluate the efficacy and toxicity profile of MRI-guided repeated SBRT (MRIg-reSBRT) in the OMD setting and propose a re-SBRT classification., Methods: We retrospectively analyzed patients (pts) with recurrent liver metastases or abdominal metastatic lesions between 1 and 5 centimeters from liver candidate to MRIg-reSBRT showing geometric overlap between the different SBRT courses and assessing whether they were in field (type 1) or not (type 2)., Results: Eighteen pts completed MRIg-reSBRT course for 25 metastatic hepatic/perihepatic lesions from July 2019 to January 2020. A total of 20 SBRT courses: 15 Type 1 re-SBRT (75%) and 5 Type 2 re-SBRT (25%) was delivered. Mean interval between the first SBRT and MRIg-reSBRT was 8,6 months. Mean prescribed dose for the first treatment was 43 Gy (range 24-50 Gy, mean BED α/β10 =93), while 41 Gy (range 16-50 Gy, mean BED α/β10 =92) for MRIg-reSBRT. Average liver dose was 3,9 Gy (range 1-10 Gy) and 3,7 Gy (range 1,6-8 Gy) for the first SBRT and MRIg-reSBRT, respectively. No acute or late toxicities were reported at a median follow-up of 10,7 months. The 1-year OS and PFS was 73,08% and 50%, respectively. Overall Clinical Benefit was 54%., Conclusions: MRIg-reSBRT could be considered an effective and safe option in the multi-integrated treatment of OMD., (© 2024. The Author(s).)

Background and Purpose: We aimed to develop and validate different machine-learning (ML) prediction models for the complete response of oligometastatic gynecological cancer after SBRT., Material and Methods: One hundred fifty-seven patients with 272 lesions from 14 different institutions and treated with SBRT with radical intent were included. Thirteen datasets including 222 lesions were combined for model training and internal validation purposes, with an 80:20 ratio. The external testing dataset was selected as the fourteenth Institution with 50 lesions. Lesions that achieved complete response (CR) were defined as responders. Prognostic clinical and dosimetric variables were selected using the LASSO algorithm. Six supervised ML models, including logistic regression (LR), classification and regression tree analysis (CART) and support vector machine (SVM) using four different kernels, were trained and tested to predict the complete response of uterine lesions after SBRT. The performance of models was assessed by receiver operating characteristic curves (ROC), area under the curve (AUC) and calibration curves. An explainable approach based on SHapley Additive exPlanations (SHAP) method was deployed to generate individual explanations of the model's decisions., Results: 63.6% of lesions had a complete response and were used as ground truth for the supervised models. LASSO strongly associated complete response with three variables, namely the lesion volume (PTV), the type of lesions (lymph-nodal versus parenchymal), and the biological effective dose (BED 10 ), that were used as input for ML modeling. In the training set, the AUCs for complete response were 0.751 (95% CI: 0.716-0.786), 0.766 (95% CI: 0.729-0.802) and 0.800 (95% CI: 0.742-0.857) for the LR, CART and SVM with a radial basis function kernel, respectively. These models achieve AUC values of 0.727 (95% CI: 0.669-0.795), 0.734 (95% CI: 0.649-0.815) and 0.771 (95% CI: 0.717-0.824) in the external testing set, demonstrating excellent generalizability., Conclusion: ML models enable a reliable prediction of the treatment response of oligometastatic lesions receiving SBRT. This approach may assist radiation oncologists to tailor more individualized treatment plans for oligometastatic patients., Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper., (Copyright © 2023 Elsevier B.V. All rights reserved.)

There is growing recognition of the importance of patient, public and community engagement in health research, which has not been used widely in analyzing health administrative datasets. In Ontario, health data are stewarded by ICES, whose strategic decision making is guided by a diverse Public Advisory Council (PAC). In a first foray into publicly led projects, the ICES PAC undertook an analysis project on mental health and addiction health service use. Public members guided the project through all stages of research. This generated critical lessons for ICES on improving participation, collaboration and trust., (Copyright © 2024 Longwoods Publishing.)

Background: HAPPY (Humanity Assurance Protocol in Interventional Radiotherapy) reports the necessity for gynecological cancer patients to undergo interventional radiotherapy (IRT, also called brachytherapy). The present paper has evaluated how some precautions may improve the psychological well-being of the patients during IRT., Methods: Patients with gynecological cancer undergoing IRT-HDR were analyzed. Patients answered three questionnaires before the IRT procedure (T0) and at the end of IRT (T1): Distress Thermometer (DT), Numerical Rating Scale for IRT procedure distress (NRS), and Hospital Anxiety and Depression Scale (HADS). Correlations have been calculated pairwise through pandas. corrwith with a Pearson algorithm, and the p-values have been calculated through scipy.stats.pearsonr. Plots have been generated through seaborn and matplotlib. A Wilcoxon test was used., Results: 55 patients were selected for this study. The median age of the patients was 64 (range, 39-84) years. 52 patients were with stage I endometrial cancer, whereas 3/3 patients with cervical cancer had locally advanced stages (IIB-IVA). 26 patients had a high education level (47.3%), and 38 were married or with a partner (69.1%). Only 14/55 (25.45%) patients were working. The HADS, DT, and NRS averages before the IRT procedure (T0) were 10.2, 3.8, and 4.3, respectively. After applying the HAPPY protocol, the HADS, DT, and NRS averages after IRT (T1) were 9.4, 3.4, and 2.6, respectively. The Wilcoxon signed rank test analysis showed a significant improvement in NRS (p < 0.00001) and HADS (p = 0.034). Living with a partner, parents or relatives was the only parameter statistically significantly associated with better DT pre-IRT (p = 0.04), HADS pre-IRT (p = 0.01), DT post-IRT (p = 0.01), and HADS post-IRT (p = 0.04)., Conclusion: In our study, the HAPPY protocol was associated with a significant reduction in patients' distress, anxiety, and discomfort., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Purpose: This retrospective, multicenter study analyzes the efficacy and safety of stereotactic body radiation therapy in a large cohort of patients with oligometastatic/persistent/recurrent uterine cancer., Methods and Materials: Clinical and radiation therapy data from several radiation therapy centers treating patients by stereotactic body radiation therapy between March 2006 and October 2021 were collected. Objective response rate was defined as complete and partial response, and clinical benefit included objective response rate plus stable disease. Radiation Therapy Oncology Group/European Organization for Research and Treatment of Cancer and Common Terminology Criteria for Adverse Events scales were used to grade toxicities. Primary endpoints were the rate of complete response to stereotactic body radiation therapy, and the 2-year actuarial local control rate "per-lesion" basis. Secondary endpoints were progression-free survival and overall survival, as well as toxicity., Results: In the study, 157 patients with oligometastatic/persistent/recurrent uterine cancer bearing 272 lesions treated by stereotactic body radiation therapy at 14 centers were analyzed. Lymph node metastases (137, 50.4%) were prevalent, followed by parenchyma lesions (135, 49.6%). Median total dose was 35 Gy (10-75.2), in 5 fractions (range, 1-10). Complete and partial responses were 174 (64.0%), and 54 (19.9%), respectively. Stable disease was registered in 29 (10.6%), and 15 (5.5%) lesions progressed. Type of lesion (lymph node), volume (≤13.7 cc) and total dose (BED 10 >59.5 Gy) were significantly associated with a higher probability of achieving complete response. Patients achieving complete response (CR) "per-lesion" basis experienced a 2-year actuarial local control rate of 92.4% versus 33.5% in lesions not achieving complete response (NCR; P < .001). Moreover, the 2-year actuarial progression-free survival rate in patients with CR was 45.4%, and patients with NCR had a 2-year rate of 17.6% (P < .001). Finally, patients who had a CR had a 2-year overall survival rate of 82.7%, compared with 56.5% for NCR patients (P <.001). Severe acute toxicity was around 2%, including one toxic death due to gastric perforation, and severe late toxicity around 4%., Conclusions: The efficacy of stereotactic body radiation therapy in this setting was confirmed. The low toxicity profile and the high local control rate in complete responder patients encourage the wider use of this approach., (Copyright © 2023 Elsevier Inc. All rights reserved.)