The therapeutic effect of radiotherapy combined with systemic therapy compared to radiotherapy alone in patients with simple brain metastasis after first-line treatment of limited-stage small cell lung cancer: a retrospective study.

PURPOSE: We aimed to compare the therapeutic effect of radiotherapy (RT) plus systemic therapy (ST) with RT alone in patients with simple brain metastasis (BM) after first-line treatment of limited-stage small cell lung cancer (LS-SCLC). METHODS: The patients were treated at a single center from January 2011 to January 2022. BM only without metastases to other organs was defined as simple BM. The eligible patients were divided into RT alone (monotherapy arm) and RT plus ST (combined therapy arm). Univariate and multivariate Cox proportional hazards analyses were used to examine factors associated with increased risk of extracranial progression. After 1:1 propensity score matching analysis, two groups were compared for extracranial progression-free survival (ePFS), PFS, overall survival (OS), and intracranial PFS (iPFS). RESULTS: 133 patients were identified and 100 were analyzed (monotherapy arm: n = 50, combined therapy arm: n = 50). The ePFS of the combined therapy was significantly longer than that of the monotherapy, with a median ePFS of 13.2 months (95% CI, 6.6-19.8) in combined therapy and 8.2 months (95% CI, 5.7-10.7) in monotherapy (P = 0.04). There were no statistically significant differences in PFS (P = 0.057), OS (P = 0.309), or iPFS (P = 0.448). Multifactorial analysis showed that combined therapy was independently associated with better ePFS compared with monotherapy (HR = 0.617, P = 0.034); more than 5 BMs were associated with worse ePFS compared with 1-5 BMs (HR = 1.808, P = 0.012). CONCLUSIONS: Compared with RT alone, combined therapy improves ePFS in patients with simple BM after first-line treatment of LS-SCLC. Combined therapy and 1-5 BMs reduce the risk of extracranial recurrence.

Holistic Person-Centered Care in Radiotherapy: Protocol for a Scoping Review.

BACKGROUND: Several types of health care professionals are responsible for the care of patients with cancer throughout their engagement with the health care system. One such type is the radiotherapist. The radiotherapist not only administers treatment but is also directly involved with the patient during treatment. Despite this direct contact with the patient, the narrative tends to focus more on technical tasks than the actual patient. This task-focused interaction is often due to the highly sophisticated equipment and complex radiotherapy treatment processes involved. This often results in not meeting the psychosocial needs of the patient, and patients have acknowledged noncompliance and delayed treatment as a result. OBJECTIVE: The scoping review aims to explore, chart, and map the available literature on holistic person-centered care in radiotherapy and to identify and present key concepts, definitions, methodologies, knowledge gaps, and evidence related to holistic person-centered care in radiotherapy. METHODS: This protocol was developed using previously described methodological frameworks for scoping studies. The review will include both peer-reviewed and gray literature regarding holistic, person-centered care in radiotherapy. A comprehensive search strategy has been developed for MEDLINE (Ovid), which will be translated into the other included databases: Scopus, CINAHL (EBSCO), MEDLINE (PubMed), Embase (Elsevier), Cochrane Library, and the Directory of Open Access Journals. Gray literature searching will include Google (Google Books and Google Scholar), ProQuest, the WorldWideScience website, the OpenGrey website, and various university dissertation and thesis repositories. The title and abstract screening, full-text review, and relevant data extraction will be performed independently by all 3 reviewers using the Covidence (Veritas Health Innovation) software, which will also be used to guide the resolution of conflicts. Sources selected will be imported into ATLAS.ti (ATLAS.ti Scientific Software Development GmbH) for analysis, which will consist of content analysis, narrative analysis, and descriptive synthesis. Results will be presented using narrative, diagrammatic, and tabular formats. RESULTS: The review is expected to identify research gaps that will inform current and future holistic, person-centered care in radiotherapy. The review commenced in November 2023, and the formal literature search was completed by the end of February 2024. Final results are expected to be published in a peer-reviewed journal by 2025. CONCLUSIONS: The findings of this review are expected to provide a wide variety of strategies aimed at providing holistic, person-centered care in radiotherapy, as well as to identify some gaps in the literature. These findings will be used to inform future studies aimed at designing, developing, evaluating, and implementing strategies toward improved holistic, person-centered care in radiotherapy. INTERNATIONAL REGISTERED REPORT IDENTIFIER (IRRID): DERR1-10.2196/51338.

Understanding therapeutic radiographers' confidence in assessing, managing & teaching radiation induced skin reactions (RISR): A national survey in the UK.

INTRODUCTION: The standard toxicity tools adopted for assessing Radiation Induced Skin Reactions (RISR) do not currently reflect how skin changes occur across all skin tones. A one size fits all approach is adopted currently for RISR assessment. The aim of this study was to understand what evidence-based practice and RISR tools are being used across the therapeutic radiography workforce and the levels of confidence in using these tools. METHODS: A survey using Likert scales to assess confidence in RISR assessment and management was made available to 77 departments in the UK between August-November 2021. Descriptive statistics were used to understand respondents' confidence in assessing, managing, and teaching RISR between white, brown, and black skin tones; Fisher's exact test was used to assess the significance of differences between groups. RESULTS: Complete responses were received from 406 therapeutic radiographers. Radiation Therapy Oncology Group (RTOG) was the most used RISR assessment tool (58% of respondents n = 237). Most respondents (74.2% n = 303) reported use of locally produced patient information on skin care, rather than the Society and College of Radiographers evidence-based patient leaflets. Confidence in assessing and managing RISR in white skin was higher than that in brown and black skin. Similarly, confidence was higher in teaching of appropriate RISR assessment and management in white skin tones when compared to brown and black skin. CONCLUSION: White skin tones appear to be more confidently assessed and managed for RISR along with taught appropriate assessment and management, than brown and black skin tones in the sample of the workforce that responded. IMPLICATIONS FOR PRACTICE: A greater understanding of the reasons for these differences is required but this study aims to instigate change and positive growth within this area.

Evaluation of safety margins for cone beam CT-based adaptive prostate radiotherapy.

Adaptive radiotherapy is characterized by the use of a daily imaging system, such as CBCT (Cone-Beam Computed Tomography) images to re-optimize the treatment based on the daily anatomy and position of the patient. By systematically re-delineating the Clinical Target Volume (CTV) at each fraction, target delineation uncertainty features a random component instead of a pure systematic. The goal of this work is to identify the random and systematic contributions of the delineation error and compute a new relevant Planning Target Volume (PTV) safety margin. 169 radiotherapy sessions from 10 prostate cancer patients treated on the Varian ETHOS treatment system have been analyzed. Intra-patient and inter-patient delineation variabilities were computed in six directions, by considering the prostate as a rigid, non-rotating volume. By doing so, we were able to directly compare the delineations done by the physicians on daily CBCT images with the initial delineation done on the CT-sim and MRI, and sort them by direction using the polar coordinates of the points. The computed variabilities were then used to compute a PTV margin based on Van Herk margin recipe. The total margin computed with random and systematic delineation uncertainties was of 2.7, 2.4, 5.6, 4.8, 4.9 and 3.6 mm in the left, right, anterior, posterior, cranial and caudal directions, respectively. According to our results, the gain offered by the separation of the delineation uncertainty into systematic and random contributions due to the adaptive delineation process justifies a reduction of the PTV margin down to 3 to 5 mm in every direction.

Inter-scanner super-resolution of 3D cine MRI using a transfer-learning network for MRgRT.

OBJECTIVE: Deep-learning networks for super-resolution (SR) reconstruction enhance the spatial-resolution of 3D magnetic resonance imaging (MRI) for MR-guided radiotherapy (MRgRT). However, variations between MRI scanners and patients impact the quality of SR for real-time 3D low-resolution (LR) cine MRI. In this study, we present a personalized super-resolution (psSR) network that incorporates transfer-learning to overcome the challenges in inter-scanner SR of 3D cine MRI. Approach: Development of the proposed psSR network comprises two-stages: 1) a cohort-specific SR (csSR) network using clinical patient datasets, and 2) a psSR network using transfer-learning to target datasets. The csSR network was developed by training on breath-hold and respiratory-gated high-resolution (HR) 3D MRIs and their k-space down-sampled LR MRIs from 53 thoracoabdominal patients scanned at 1.5 T. The psSR network was developed through transfer-learning to retrain the csSR network using a single breath-hold HR MRI and a corresponding 3D cine MRI from 5 healthy volunteers scanned at 0.55 T. Image quality was evaluated using the peak-signal-noise-ratio (PSNR) and the structure-similarity-index-measure (SSIM). The clinical feasibility was assessed by liver contouring on the psSR MRI using an auto-segmentation network and quantified using the Dice-similarity-coefficient (DSC). Results. Mean PSNR and SSIM values of psSR MRIs were increased by 57.2% (13.8 to 21.7) and 94.7% (0.38 to 0.74) compared to cine MRIs, with the reference 0.55 T breath-hold HR MRI. In the contour evaluation, DSC was increased by 15% (0.79 to 0.91). Average time consumed for transfer-learning was 90 s, psSR was 4.51 ms per volume, and auto-segmentation was 210 ms, respectively. Significance. The proposed psSR reconstruction substantially increased image and segmentation quality of cine MRI in an average of 215 ms across the scanners and patients with less than 2 minutes of prerequisite transfer-learning. This approach would be effective in overcoming cohort- and scanner-dependency of deep-learning for MRgRT. .

Patient-reported outcomes after personalised dose-escalation for stage II-III non-small-cell lung cancer patients: Results from the randomised ARTFORCE PET-Boost trial.

BACKGROUND AND PURPOSE: The ultimate challenge in dose-escalation trials lies in finding the balance between benefit and toxicity. We examined patient-reported outcomes (PROs), including health-related quality of life (HRQoL) in patients with locally advanced non-small cell lung cancer (LA-NSCLC), treated with dose-escalated radiotherapy. MATERIALS AND METHODS: The international, randomised, phase 2 ARTFORCE PET-Boost study (NCT01024829) aimed to improve 1-year freedom from local failure rates in patients with stage II-III NSCLC, with a ≥ 4 cm primary tumour. Treatment consisted of an individualised, escalated fraction dose, either to the primary tumour as a whole or to its most FDG-avid subvolume (24 x 3.0-5.4 Gy). Patients received sequential or concurrent chemoradiotherapy, or radiotherapy only. Patients were asked to complete the EORTC QLQ-C30, QLQ-LC13, and the EuroQol-5D at eight timepoints. We assessed the effect of dose-escalation on C30 sum score through mixed-modelling and evaluated clinically meaningful changes for all outcomes. RESULTS: Between Apr-2010 and Sep-2017, 107 patients were randomised; 102 were included in the current analysis. Compliance rates: baseline 86.3%, 3-months 85.3%, 12-months 80.3%; lowest during radiation treatment 35.0%. A linear mixed-effect (LME) model revealed no significant change in overall HRQoL over time, and no significant difference between the two treatment groups. Physical functioning showed a gradual decline in both groups during treatment and at 18-months follow-up, while clinically meaningful worsening of dyspnoea was seen mainly at 3- and 6-months. CONCLUSION: In patients with LA-NSCLC treated with two dose-escalation strategies, the average patient-reported HRQoL remained stable in both groups, despite frequent patient-reported symptoms, including dyspnoea, dysphagia, and fatigue.

Myeloid-derived suppressor cells attenuate the antitumor efficacy of radiopharmaceutical therapy using 90Y-NM600 in combination with androgen deprivation therapy in murine prostate tumors.

RATIONALE: Androgen deprivation therapy (ADT) is pivotal in treating recurrent prostate cancer and is often combined with external beam radiation therapy (EBRT) for localized disease. However, for metastatic castration-resistant prostate cancer, EBRT is typically only used in the palliative setting, because of the inability to radiate all sites of disease. Systemic radiation treatments that preferentially irradiate cancer cells, known as radiopharmaceutical therapy or targeted radionuclide therapy (TRT), have demonstrable benefits for treating metastatic prostate cancer. Here, we explored the use of a novel TRT, 90Y-NM600, specifically in combination with ADT, in murine prostate tumor models. METHODS: 6-week-old male FVB mice were implanted subcutaneously with Myc-CaP tumor cells and given a single intravenous injection of 90Y-NM600, in combination with ADT (degarelix). The combination and sequence of administration were evaluated for effect on tumor growth and infiltrating immune populations were analyzed by flow cytometry. Sera were assessed to determine treatment effects on cytokine profiles. RESULTS: ADT delivered prior to TRT (ADT→TRT) resulted in significantly greater antitumor response and overall survival than if delivered after TRT (TRT→ADT). Studies conducted in immunodeficient NRG mice failed to show a difference in treatment sequence, suggesting an immunological mechanism. Myeloid-derived suppressor cells (MDSCs) significantly accumulated in tumors following TRT→ADT treatment and retained immune suppressive function. However, CD4+ and CD8+ T cells with an activated and memory phenotype were more prevalent in the ADT→TRT group. Depletion of Gr1+MDSCs led to greater antitumor response following either treatment sequence. Chemotaxis assays suggested that tumor cells secreted chemokines that recruited MDSCs, notably CXCL1 and CXCL2. The use of a selective CXCR2 antagonist, reparixin, further improved antitumor responses and overall survival when used in tumor-bearing mice treated with TRT→ADT. CONCLUSION: The combination of ADT and TRT improved antitumor responses in murine models of prostate cancer, however, this was dependent on the order of administration. This was found to be associated with one treatment sequence leading to an increase in infiltrating MDSCs. Combining treatment with a CXCR2 antagonist improved the antitumor effect of this combination, suggesting a possible approach for treating advanced human prostate cancer.

Progression-directed Therapy in Oligoprogressive Castration-resistant Prostate Cancer: Final Results from the Prospective, Single-arm, Phase 2 MEDCARE Trial.

BACKGROUND AND OBJECTIVE: Next-line systemic treatment (NEST) is the standard of care for patients presenting with progressive metastatic castration-resistant prostate cancer (mCRPC). Progression-directed therapy (PDT), defined as a lesion-directed approach in patients with a limited number of progressive and/or new lesions, could postpone the need for NEST in these patients with so-called oligoprogressive mCRPC. Our aim was to investigate the feasibility of postponing NEST initiation in oligoprogressive mCRPC by using PDT. METHODS: MEDCARE was a prospective, single-arm, nonrandomized phase 2 trial. Eligible patients had oligoprogressive mCRPC and were treated with PDT while their ongoing systemic therapy was continued. The primary endpoint was NEST-free survival (NEST-FS). Secondary endpoints were prostate-specific antigen response, clinical progression-free survival (cPFS), prostate cancer-specific survival (PCSS), overall survival (OS), and PDT-induced toxicity. KEY FINDINGS AND LIMITATIONS: Twenty patients underwent PDT for 38 oligoprogressive lesions. At median follow-up of 28 mo, median NEST-FS was 17 mo and the 2-yr NEST-FS rate was 35%. Median PCSS and median OS were not reached. The PCSS and OS rates at 2 yr were 80% and 70%, respectively. The 2-yr local control rate was 95%. No patient experienced early or late grade ≥3 toxicity. NEST-FS was longer for patients who received PDT to all lesions visible on 18F-PSMA positron emission tomography/computed tomography (30 vs 13 mo; p = 0.002). CONCLUSIONS AND CLINICAL IMPLICATIONS: This single-center, single-arm, phase 2 trial demonstrated that PDT in oligoprogressive mCRPC resulted in median NEST-FS of 17 mo without any early or late grade ≥3 toxicity. PATIENT SUMMARY: For patients with metastatic prostate cancer no longer responding to hormone therapy, we investigated radiotherapy targeted at progressive cancer lesions while continuing their ongoing systemic treatment. The results show that this targeted therapy had very low toxicity and delayed the need to start a new line of systemic treatment by 17 months.

Comparative Analysis of Stereotactic Radiation Therapy and Conventional Radiation Therapy in Cancer Pain Control: A Systematic Review and Meta-Analysis.

AIMS: Approximately 55% of patients diagnosed with primary or metastatic cancer endure pain directly attributable to the disease. Consequently, it becomes imperative to address pain management through a comparative analysis of stereotactic radiotherapy (SRT) and conventional radiation therapy (CRT), especially in light of the less efficacious improvement achieved solely through pharmacological interventions. MATERIALS AND METHODS: A systematic exploration was undertaken on PubMed, the Cochrane Library, and Elsevier's ScienceDirect databases to identify studies that compare Stereotactic Radiotherapy to Conventional radiation therapy for pain management in individuals with metastatic bone cancer. The analyses were executed utilizing the random-effects model. RESULTS: A cohort of 1152 participants with metastatic bone cancer was analyzed, demonstrating significantly higher complete pain relief in the Stereotactic Radiotherapy group during both early and late follow-up (RR: 1.61; 95% CI: 1.17, 2.23, p-value: 0.004; I2: 0%). Stereotactic Radiotherapy also showed a non-significant increase in the incidence of partial pain relief (RR: 1.07; 95% CI: 0.85, 1.34, p-value: 0.56; I2: 18%). Furthermore, Stereotactic Radiotherapy was associated with a significantly reduced risk of stationary pain throughout follow-up (RR: 0.61; 95%CI: 0.48, 0.76, p-value: <0.0001; I2: 0. The incidence of progressive pain was non-significantly reduced with Stereotactic Radiotherapy during both early and late follow-up (RR: 0.77; 95% CI: 0.50, 1.17, p-value: 0.22; I2: 0%). Secondary outcomes exhibited a non-significant trend favoring Stereotactic Radiotherapy for dysphagia, esophagitis, pain, and radiodermatitis, while a non-significant increase was observed for nausea, fatigue, and vertebral compression fracture. CONCLUSION: In summary, stereotactic radiation therapy (SRT) has improved in achieving complete pain relief while exhibiting a decreased probability of delivering stationary pain compared to conventional radiation therapy (CRT). Nevertheless, it is crucial in future research to address a noteworthy limitation, specifically, the risk of vertebral compression fracture.

Patterns of Failure After Prostate-Only Radiotherapy in High-Risk Prostate Cancer: Implications for Refining Pelvic Nodal Contouring Guidelines.

PURPOSE: To study prostate specific membrane antigen - positron emission tomography (Ga68PSMA-PETCT) based patterns of relapse at biochemical failure (BCF) after prostate-only radiotherapy (PORT) in high-risk (HR) prostate cancer and its implications on pelvic contouring recommendations. METHODS AND MATERIALS: Patients with clinico-radiological high-risk node-negative prostate cancer treated with curative PORT and androgen deprivation therapy (ADT), either within the POP-RT randomised trial or off trial, who underwent a Ga68PSMA-PETCT upon BCF were included. Patterns of regional and distant recurrence on Ga68PSMA-PETCT were studied. Pelvic nodal recurrences were mapped with reference to the superior border of pubic symphysis. Pelvic lymph nodal caudal border (PLNcb) recommendations in the published contouring guidelines (RTOGcb, GETUGcb, PIVOTALcb, NRGcb, GFRUcb) were evaluated. RESULTS: Of the total 262 patients screened, 68 eligible patients were included (POP-RT trial 35 patients; off-trial 33 patients). Median follow-up was 91 months (IQR, 72-117) and median time to BCF was 65 months (IQR, 49-83). Regional and distant recurrence was seen in 31 (46%) and 31 (46%) patients, respectively. Of the nodal recurrences, nearly half (46%, 14/31) had no distant metastases and 64% (20/31) had a failure in the common iliac nodal region. The lower-most nodal recurrence was 20 mm cranial to the top of pubic symphysis (RTOGcb, GETUGcb, GFRUcb) and 10 mm cranial to the PIVOTALcb. The PLNcb recommended by NRG guideline (NRGcb) had an inter-patient variability of 32 mm, ranging from 16 mm above to 16 mm below the top of pubic symphysis, and the lower most nodal recurrence ranged from 4 mm to 36 mm cranial to NRGcb. CONCLUSION: Pelvic failures accounted for a major proportion of recurrences after prostate-only radiotherapy, with the caudal most nodal recurrence being 20 mm cranial to the top of pubic symphysis. This could have implications in defining the caudal border of contouring recommendations.

Pelvic target volume inter-fractional motion during radiotherapy for cervical cancer with daily iterative cone beam computed tomography.

BACKGROUND: Tumor regression and organ movements indicate that a large margin is used to ensure target volume coverage during radiotherapy. This study aimed to quantify inter-fractional movements of the uterus and cervix in patients with cervical cancer undergoing radiotherapy and to evaluate the clinical target volume (CTV) coverage. METHODS: This study analyzed 303 iterative cone beam computed tomography (iCBCT) scans from 15 cervical cancer patients undergoing external beam radiotherapy. CTVs of the uterus (CTV-U) and cervix (CTV-C) contours were delineated based on each iCBCT image. CTV-U encompassed the uterus, while CTV-C included the cervix, vagina, and adjacent parametrial regions. Compared with the planning CTV, the movement of CTV-U and CTV-C in the anterior-posterior, superior-inferior, and lateral directions between iCBCT scans was measured. Uniform expansions were applied to the planning CTV to assess target coverage. RESULTS: The motion (mean ± standard deviation) in the CTV-U position was 8.3 ± 4.1 mm in the left, 9.8 ± 4.4 mm in the right, 12.6 ± 4.0 mm in the anterior, 8.8 ± 5.1 mm in the posterior, 5.7 ± 5.4 mm in the superior, and 3.0 ± 3.2 mm in the inferior direction. The mean CTV-C displacement was 7.3 ± 3.2 mm in the left, 8.6 ± 3.8 mm in the right, 9.0 ± 6.1 mm in the anterior, 8.4 ± 3.6 mm in the posterior, 5.0 ± 5.0 mm in the superior, and 3.0 ± 2.5 mm in the inferior direction. Compared with the other tumor (T) stages, CTV-U and CTV-C motion in stage T1 was larger. A uniform CTV planning treatment volume margin of 15 mm failed to encompass the CTV-U and CTV-C in 11.1% and 2.2% of all fractions, respectively. The mean volume change of CTV-U and CTV-C were 150% and 51%, respectively, compared with the planning CTV. CONCLUSIONS: Movements of the uterine corpus are larger than those of the cervix. The likelihood of missing the CTV is significantly increased due to inter-fractional motion when utilizing traditional planning margins. Early T stage may require larger margins. Personal radiotherapy margining is needed to improve treatment accuracy.

The efficacy and safety of short-course radiotherapy followed by sequential chemotherapy and Cadonilimab for locally advanced rectal cancer: a protocol of a phase II study.

BACKGROUND: For patients with locally advanced rectal cancer (LARC), total neoadjuvant therapy (TNT), namely, intensifying preoperative treatment through the integration of radiotherapy and systemic chemotherapy before surgery, was commonly recommended as the standard treatment. However, the risk of distant metastasis at 3 years remained higher than 20%, and the complete response (CR) rate was less than 30%. Several clinical trials had suggested a higher complete response rate when combining single-agent immunotherapy with short-course radiotherapy (SCRT). The CheckMate 142 study had shown encouraging outcomes of dual immunotherapy and seemingly comparable toxicity for CRC compared with single-agent immunotherapy in historical results. Therefore, dual immunotherapy might be more feasible in conjunction with the TNT paradigm of SCRT. We performed a phase II study to investigate whether the addition of a dual immune checkpoint inhibitor bispecific antibody, Cadonilimab, to SCRT combined with chemotherapy might further increase the clinical benefit and prognosis for LARC patients. METHODS: This single-arm, multicenter, prospective, phase II study included patients with pathologically confirmed cT3-T4N0 or cT2-4N + rectal adenocarcinoma with an ECOG performance score of 0 or 1. Bispecific antibody immunotherapy was added to SCRT combined with chemotherapy. Patients enrolled would be treated with SCRT (25 Gy in five fractions over 1 week) for the pelvic cavity, followed by 4 cycles of CAPOX or 6 cycles of mFOLFOX and Cadonilimab. The primary endpoint was the CR rate, which was the ratio of the pathological CR rate plus the clinical CR rate. The secondary endpoints included local-regional control, distant metastasis, disease-free survival, overall survival, toxicity profile, quality of life and functional outcome of the rectum. To detect an increase in the complete remission rate from 21.8% to 40% with 80% power, 50 patients were needed. DISCUSSION: This study would provide evidence on the efficacy and safety of SCRT plus bispecific antibody immunotherapy combined with chemotherapy as neoadjuvant therapy for patients with LARC, which might be used as a candidate potential therapy in the future. TRIAL REGISTRATION: This phase II trial was prospectively registered at ClinicalTrials.gov, under the identifier NCT05794750.

The effectiveness of adjustable trans-obturator male system (ATOMS) in radiated patients is reduced: A propensity score-matched analysis.

Objectives: This study aimed to compare the effectiveness and safety of the adjustable trans-obturator male system (ATOMS®) to treat post-prostatectomy incontinence (PPI) in radiated patients compared with non-radiated patients, using propensity score-matching analysis to enhance the validity of the comparison. Patients and methods: Consecutive men with PPI treated with silicone-covered scrotal port ATOMS (A.M.I., Feldkirch, Austria) in nine different institutions between 2016 and 2022 were included. Preoperative assessment evaluated 24-h pad usage, urethroscopy and urodynamics, if indicated. Propensity score-matching analysis was based on age, length of follow-up, previous PPI treatment, previous bladder neck stricture, androgen deprivation and pad usage. The primary endpoint was dry rate, defined as no pads post-operatively with a security pad allowed. The secondary endpoints were complications, device removal and self-perceived satisfaction with the Patient Global Impression of Improvement (PGI-I) scale. Results: Of the 710 included patients, 342 were matched, and the study groups were balanced for the baseline matched variables. The mean baseline 24-h pad was 4.8 in both groups (p = 0.48). The mean follow-up was 27.5 ± 18.6 months, which was also equivalent between groups (p = 0.36). The primary outcome was achieved in 73 (42.7%) radiated patients and in 115 (67.3%) non-radiated patients (p < 0.0001). The mean pad count at the last follow-up was 1.5 and 0.8, respectively (p < 0.0001). There was no significant difference in complications (p = 0.94), but surgical revision and device explant rates were higher (p = 0.03 and p = 0.01, respectively), and the proportion of patients highly satisfied (PGI-I = 1) was lower in the radiated group (p = 0.01). At sensitivity analysis, the study was found to be reasonably robust to hidden bias. Conclusion: ATOMS implantation significantly outperformed in patients without adjuvant radiation over radiated patients.

Unraveling a Rare Case of Epidural Extramedullary Hematopoiesis in a Patient With Transfusion-Dependent Beta Thalassemia Presenting With Spinal Cord Compression.

Thalassemia is known to induce extramedullary hematopoiesis (EMH), which is a compensatory mechanism in which the body forms blood cells outside the bone marrow. While EMH typically affects organs such as the spleen and liver, there are rare instances where it leads to spinal cord compression (SCC) in the epidural space. A 31-year-old male patient with transfusion-dependent beta thalassemia presented with numbness and bilateral limb weakness due to EMH. Neurological examination revealed increased tone in both legs, reduced power, loss of crude touch and pain sensation, and increased deep tendon reflexes. Magnetic resonance imaging (MRI) indicated a lobulated soft tissue structure in the posterior dural intrathecal space causing SCC. Laminectomy of the T2-T8 vertebrae was done, after which the lesion was identified and completely removed. Post-surgery, significant neurological improvements were observed in both motor and sensory functions. Thalassemia patients presenting with symptoms of SCC should be investigated for the presence of epidural EMH. Treatment options include decompressive surgery, blood transfusions, hydroxyurea, and radiotherapy.

Case report: Characteristics and nature of primary cardiac synovial sarcoma.

Primary malignant cardiac tumors rarely occur, and cardiac synovial sarcoma (SS) is especially rare among such tumors. Herein, we present the case of a 35-year-old female with primary cardiac SS treated with surgery, chemotherapy, and radiotherapy. She presented with chest symptoms and underwent imaging examinations. A cardiac tumor was suspected, and an open biopsy was performed. The pathological findings suggested cardiac SS. Next, we performed a resection, and the tumors persisted at a macroscopic level. Immunohistochemistry was negative for SS18-SSX and positive for the SSX C-terminus and cytokeratin CAM5.2, a reduction of SMARCB1/INI1 was observed, and fluorescence in situ hybridization showed positive SS18 split staining. Owing to the FNCLCC grade 3 tumor and R2 margins, adjuvant chemotherapy with ifosfamide, doxorubicin, and radiotherapy was initiated, and the patient was diagnosed with cardiac SS. The differences in patients with cardiac SS compared with general SS include male predominance, larger tumor size, and poorer prognosis. Pathological findings of immunohistochemistry and fluorescence in situ hybridization were found to be more reliable than imaging findings for a correct diagnosis. Additionally, because incomplete resection is frequently performed, adjuvant therapy, including chemotherapy and radiation therapy, may be performed. The findings indicate that multiple therapies, including surgery, chemotherapy, and radiotherapy, are essential treatment strategies for improving the prognosis of patients with cardiac SS.

Long-term efficacy analysis of radiotherapy and local management of metastases in patients with newly diagnosed oligometastatic nasopharyngeal carcinoma: A prospective, single-arm, single-center clinical study.

PURPOSE: We conducted a single-center, single-arm study (NCT03129412) to prospectively analyze the long-term outcomes of newly diagnosed patients with oligometastatic nasopharyngeal carcinoma (NPC) who received radical radiotherapy and local treatment of metastases. PATIENTS AND METHODS: Patients who reached disease controll after platinum-based palliative chemotherapy continued to receive radical radiotherapy for the nasopharyngeal region and neck. Appropriate local treatments were selected to treat the metastatic lesions. The primary endpoint of this study was overall survival (OS) and the secondary endpoint was progression-free survival (PFS). RESULTS: Fifty-one patients were included in the final analysis. During a median follow-up of 60 months, the median OS and PFS were 53.87 and 24.23 months, respectively. The 1-year, 3-year, and 5-year PFS and OS rates were 76.5 %, 38.1 %, and 31.8 % and 98 %, 75.4 %, 45.6 %, respectively. Both single and multivariate analysis indicated that maintenance therapy after radiotherapy could significantly increase PFS (36.43 vs. 16.1 months, P = 0.005). The OS of patients with single organ metastasis was significantly better than that of patients with double organ metastasis (P = 0.001). In addition, the number of metastatic organs also significantly affected PFS in the multifactor analysis. CONCLUSION: Patients with newly diagnosed oligometastatic NPC can achieve long-term survival after receiving radical radiotherapy to the primary site and local treatment for metastases.

Long-Term Second Malignancies in Prostate Cancer Patients Treated With Low-Dose-Rate Brachytherapy and Radical Prostatectomy.

PURPOSE: Second malignancy is a rare but potentially lethal event after prostate brachytherapy, but data remain scarce on its long-term risk. The objective of this study is to estimate the number of pelvic second malignancies following brachytherapy compared to radical prostatectomy (RP). MATERIALS AND METHODS: We retrospectively reviewed patients treated with low-dose 125I brachytherapy and RP in British Columbia from 1999 to 2010. Kaplan-Meier estimates for pelvic (bladder and rectum), invasive pelvic, any second malignancy, and death from any second malignancy were assessed. Cox multivariable analyses were performed adjusting for initial treatment type, age, post-RP adjuvant/salvage external beam radiation therapy status, and smoking history. RESULTS: Two thousand three hundred seventy-eight brachytherapy and 9089 RP patients were included. Median age was 66 years (interquartile range [IQR] 61-71) and 63 years (IQR 58-67), respectively. Median follow-up time to event or censured was 14 years (IQR 11.5-17.3). The Kaplan-Meier estimates for pelvic second malignancy at 15 and 20 years were 6.4% and 9.8%, respectively, after brachytherapy, and 3.2% and 4.2% after RP. Time to any second malignancy and time to death from any second malignancy were not significantly different (P > .05). On Cox multivariable analysis, brachytherapy, compared to surgery, was an independent factor for pelvic (hazard ratio [HR] 1.81 [95% CI 1.45-2.26], P < .001) and invasive pelvic second malignancy (HR 2.13 [95% CI 1.61-2.83], P < .001). Increased age and smoking were also associated with higher estimates of events (P < .001). CONCLUSIONS: After adjustment for age, post-RP adjuvant/salvage external beam radiation therapy status, and smoking status, numerically higher long-term HRs of pelvic and invasive pelvic second malignancy in patients treated with brachytherapy compared to RP were noted.

Effect of radiotherapy on the surface roughness and microhardness of contemporary bioactive restorative materials.

OBJECTIVE: The aim of this in vitro study was to evaluate the effect of radiotherapy on the surface microhardness and roughness of different bioactive restorative materials. MATERIALS AND METHODS: A total of 60-disc specimens (5 mm × 2 mm) were performed in four groups (n = 15 each) from Equia Forte HT, Cention N, Activa Bioactive Restorative, and Beautifil II. Following the polishing procedure (600, 1000, 1200 grit silicon carbide papers), all specimens were irradiated at 2 Gy per fraction, five times a week for a total dose of 70 Gy in 30 fractions over 7 weeks. Before and after the irradiation, the specimens were analyzed regarding the surface roughness and microhardness. Surface morphology was also analyzed by scanning electron microscopy. Kruskal-Wallis test, Wilcoxon test, and paired sample t-test were used for statistical analysis. RESULTS: Significant differences were found after radiation with increased mean roughness of both Cention N (p = 0.001) and Beautifil II (p < 0.001) groups. In terms of microhardness, only the Beautifil II group showed significant differences with decreased values after radiation. There were statistically significant differences among the groups' roughness and microhardness data before and after radiotherapy (p < 0.05). CONCLUSION: The effect of radiotherapy might differ according to the type of the restorative material. Although results may differ for other tested materials, giomer tends to exhibit worse behaviour in terms of both surface roughness and microhardness. CLINICAL RELEVANCE: In patients undergoing head and neck radiotherapy, it should be taken into consideration that the treatment process may also have negative effects on the surface properties of anti-caries restorative materials.

Anti-PD-1 antibody in combination with radiotherapy as first-line therapy for unresectable intrahepatic cholangiocarcinoma.

BACKGROUND: Unresectable intrahepatic cholangiocarcinoma (iCCA) has a poor prognosis despite treatment with standard combination chemotherapy. We aimed to evaluate the efficacy and safety of radiotherapy in combination with an anti-PD-1 antibody in unresectable iCCA without distant metastases. METHODS: In this phase II study, patients with histopathologically confirmed unresectable primary or postoperative recurrent iCCA without distant metastases were enrolled. Patients received external radiotherapy with a dose of ≥45 Gy (2-2.5 Gy per fraction), followed by anti-PD-1 immunotherapy (camrelizumab 200 mg once, every 3 weeks) initiated within 7 days after completion of radiotherapy as first-line therapy. The primary endpoint was 1-year progression-free survival (PFS) rate. The secondary end points included safety, objective response rate (ORR), disease control rate (DCR), and overall survival (OS). RESULTS: From December 2019 to March 2021, 36 patients completed radiotherapy and at least one cycle of immunotherapy and were included in efficacy and safety analyses. The median follow-up was 19.0 months (IQR 12.0-24.0), and the one-year PFS rate was 44.4% (95% CI, 30.8-64.0). The median PFS was 12.0 months (95% CI, 7.5-not estimable); the median OS was 22.0 months (95% CI, 15.0-not estimable). The ORR was 61.1% and the DCR was 86.1%. Seventeen of 36 (47.2%) patients experienced treatment-related adverse effects (AEs) of any grade. The most common AE was reactive cutaneous capillary endothelial proliferation (25.0%). Five (13.9%) patients experienced grade ≥3 treatment-related AEs, including decreased lymphocyte (5.6%), bullous dermatitis (2.8%), decreased platelet count (2.8%), and deep-vein thrombosis (2.8%). CONCLUSIONS: External radiotherapy plus camrelizumab, as first-line therapy, met its primary endpoint and showed antitumor activity and low toxicity levels in patients with unresectable iCCA without distant metastases, warranting further investigation. TRIAL REGISTRATION: NCT03898895. Registered 2 April 2019.