PURPOSE: The presence of MYC and BCL2 translocations (ie, double-hit lymphoma, DHL) in large B-cell lymphoma (LBCL) is associated with reduced chemosensitivity, but less is known on its impact on radiotherapy (RT) efficacy. METHODS AND MATERIALS: Patients with LBCL who received their first course of RT for relapsed/refractory disease between 2008 and 2020 were eligible if there was adequate pathologic evaluation to be categorized as DHL versus non-DHL as per the World Health Organization (fifth edition). Separate analyses were conducted by treatment intent. Predictors for response (complete and partial) and local recurrence (LR) were evaluated using Cox regression analysis. LR analysis was restricted to curative-intent patients to ensure adequate follow-up. RESULTS: Three hundred and eighty-three patients (102 DHL, 281 non-DHL, and 44% curative) were treated at 447 sites. Median time from diagnosis to RT was 11.6 months, with 38.7% of patients having primary chemorefractory disease, 37.4% having received >2 lines of systemic therapy, and 24% status post-stem cell transplant. Median biological equivalent dose (alpha/beta: 10) was 28 Gy (range: 3.2-60.0) for palliative and 46.9 Gy (range: 6.4-84.0) for curative-intent patients. With a median follow-up of 41.1 and 41.5 months among curative and palliative patients, respectively, the response was high (81.1% curative, 60.1% palliative). On univariate analysis, DHL pathology was not associated with RT response in either curative or palliative patients. Among curative patients, 2-year LR rate was 38.8%. On multivariable analysis, DHL pathology was associated with a 2 times higher risk of LR (95% CI: 1.05-3.67, P = .03), with a crude LR rate of 42.9% (DHL) versus 28.9% (non-DHL). RT was well tolerated with low rates of grade 3 or higher acute toxicity (1.8% curative, 2.9% palliative). CONCLUSIONS: Relapsed/refractory LBCL remains radioresponsive with a 60%-80% response rate to RT. Although DHL pathology does not appear to influence RT response, its presence is associated with higher rates of LR, suggesting that it may be more radioresistant.

• MeSH
• Lymphoma, Large B-Cell, Diffuse * radiotherapy   pathology   genetics   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Neoplasm Recurrence, Local * pathology   MeSH
• Young Adult MeSH
• Proto-Oncogene Proteins c-bcl-2 genetics   MeSH
• Proto-Oncogene Proteins c-myc genetics   MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Translocation, Genetic MeSH
• Treatment Outcome MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Young Adult MeSH
• Male MeSH
• Aged, 80 and over MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH
• Multicenter Study MeSH

PURPOSE OF REVIEW: This review explores the design and endpoints of perioperative platforms in clinical trials for muscle-invasive bladder cancer (MIBC). RECENT FINDINGS: The choice of clinical trial design in perioperative platforms for MIBC must align with specific research objectives to ensure robust and meaningful outcomes. Novel designs in perioperative platforms for MIBC integrate bladder-sparing approaches. Primary endpoints such as pathological complete response and disease-free survival are highlighted for their role in expediting trial results in perioperative setting. Incorporating patient-reported outcomes is important to inform healthcare decision makers about the outcomes most meaningful to patients. Given the growing body of evidence, potential biomarkers, predictive and prognostic tools should be considered and implemented when designing trials in perioperative platforms for MIBC. SUMMARY: Effective perioperative platforms for MIBC trials are critical in enhancing patient outcomes. The careful selection and standardization of study designs and endpoints in the perioperative platform are essential for the successful implementation of new therapies and the advancement of personalized treatment approaches in MIBC.

• MeSH
• Cystectomy methods   adverse effects   MeSH
• Neoplasm Invasiveness * MeSH
• Clinical Trials as Topic MeSH
• Humans MeSH
• Urinary Bladder Neoplasms * surgery   pathology   therapy   mortality   MeSH
• Perioperative Care methods   standards   MeSH
• Endpoint Determination MeSH
• Treatment Outcome MeSH
• Research Design MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

Uroteliální karcinom patří v raných stadiích k nejčastějším nádorovým onemocněním, onkolog se však častěji setkává s pacienty s pokročilým onemocněním. Právě metastatický uroteliální karcinom zůstává velkou terapeutickou výzvou. Tradiční léčba byla a stále je postavena na chemoterapii obsahující platinový derivát, avšak za poslední roky i tato diagnóza prošla velkým vývojem a do léčby přibyly nové léky ze skupiny moderní imunoterapie. Zcela zásadní zlom pak přinesly kombinované režimy imunoterapie s konjugovanými protilátkami, kdy kombinace pembrolizumabu s enfortumab vedotinem přepsala doporučené postupy léčby uroteliálního karcinomu v první linii. Právě kombinovaná terapie se stane budoucností managementu uroteliálního karcinomu, tak jako je to patrné i u jiných nádorových onemocnění.

Muscle-invasive bladder cancer (MIBC) is an aggressive malignancy with a high risk of metastases and recurrence. The standard treatment involves neoadjuvant cisplatin-based chemotherapy followed by radical cystectomy, yet approximately 50 % of patients relapse within three years. Neoadjuvant chemotherapy improves overall survival (OS) and pathological complete response (pCR). Emerging treatment strategies include neoadjuvant immunotherapy, with phase II trials demonstrating increased pCR rates with pembrolizumab and atezolizumab. The recently published NIAGARA trial established that perioperative durvalumab combined with chemotherapy reduces disease progression risk by 32 % (HR = 0.68) and mortality risk by 25 % (HR = 0.75). This supports perioperative immunotherapy as the new standard of care. Ongoing studies focus on combining ADCs and ICIs and leveraging ctDNA to refine patient selection. These advancements drive personalized oncology and optimize neoadjuvant therapy.

• MeSH
• Circulating Tumor DNA MeSH
• Immunotherapy methods   MeSH
• Humans MeSH
• Urinary Bladder Neoplasms * drug therapy   MeSH
• Neoadjuvant Therapy MeSH
• Intraoperative Care MeSH
• Antineoplastic Combined Chemotherapy Protocols MeSH
• Randomized Controlled Trials as Topic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

CONTEXT: Several phase III randomized controlled trials (RCTs) have shown the importance of perioperative systemic therapy, especially for the efficacy of immune checkpoint inhibitors (ICIs) in both neoadjuvant and adjuvant settings for muscle-invasive bladder cancer (MIBC). OBJECTIVE: To synthesize the growing evidence on the efficacy and safety of systemic therapies for MIBC utilizing the data from RCTs. EVIDENCE ACQUISITION: Three databases and ClinicalTrials.gov were searched in October 2024 for eligible RCTs evaluating oncologic outcomes in MIBC patients treated with systemic therapy. We evaluated pathological complete response (pCR), disease-free survival (DFS), progression-free survival (PFS), event-free survival (EFS), overall survival (OS), and adverse events (AEs). EVIDENCE SYNTHESIS: Thirty-three RCTs (including 14 ongoing trials) were included in this systematic review. Neoadjuvant chemotherapy improved OS compared to radical cystectomy alone. Particularly, the VESPER trial demonstrated that dd-MVAC provided oncological benefits over GC alone in terms of pCR rates, OS (HR: 0.71), and PFS (HR: 0.70). Recently, the NIAGARA trial showed that perioperative durvalumab plus GC outperformed GC alone in terms of pCR rates, OS (HR: 0.75), and EFS (HR: 0.68). Despite the lack of data on overall AE rates in the VESPER trial, differential safety profiles in hematologic toxicity were reported between dd-MVAC and durvalumab plus GC regimens. In the adjuvant setting, no study provided the OS benefit from adjuvant chemotherapy. However, only adjuvant nivolumab had significant DFS and OS benefits compared to placebo. CONCLUSIONS: Neoadjuvant chemotherapy remains the current standard of care for MIBC. Durvalumab shed light on the promising impact of ICIs added to neoadjuvant chemotherapy. Nivolumab is the only ICI recommended as adjuvant therapy in patients who harbored adverse pathologic outcomes. Ongoing trials will provide further information on the impact of combination therapy, including chemotherapy, ICIs, and enfortumab vedotin, in both neoadjuvant and adjuvant settings.

• Publication type
• Journal Article MeSH
• Review MeSH

Strategie watch-and-wait (WW) nabízí u vybraných pacientů s distálním adenokarcinomem rekta alternativu k radikální resekci s totální mezorektální excizí (TME) po dosažení kompletní klinické odpovědi (complete clinical response – cCR) na neoadjuvantní terapii. Tento přístup je založen na intenzivním sledování, kdy je multidisciplinární tým, zejména chirurg, konfrontován s náročným follow-up režimem zahrnujícím opakované anorektoskopie, per rectum vyšetření a magnetické rezonance. Problematická je především predikce patologické kompletní odpovědi v případě cCR. Klíčovým faktorem je riziko recidivy (regrowth) u cCR, která se vyskytuje u 26–36 % pacientů zejména během prvních 3 let sledování a zvyšuje riziko vzniku metastáz. Včasná salvage R0 resekce je indikována při detekci regrowth a je proveditelná ve více než 90 % případů. WW nabízí u compliantních pacientů srovnatelné onkologické výsledky a lepší funkční výsledky ve srovnání s TME u pacientů s pCR.

Watch-and-wait (WW) strategy offers an alternative to radical resection with total mesorectal excision (TME) in selected patients with distal rectal adenocarcinoma after achieving complete clinical response (cCR) to neoadjuvant therapy. This approach is based on intensive follow-up, where a multidisciplinary team, especially the surgeon, is confronted with a demanding follow-up regimen including repeated anorectoscopies, per rectum examinations and magnetic resonance imaging. The prediction of pathological complete response in cCR is particularly problematic. The risk of recurrence (regrowth) in cCR is a key factor, which occurs in 26–36% of patients, especially during the first 3 years of follow-up, and increases the risk of metastasis. Early salvage R0 resection is indicated when regrowth is detected and is feasible in more than 90% of cases. WW offers comparable oncologic outcomes in compliant patients and better functional outcomes compared to TME in patients with pCR.

• MeSH
• Clinical Decision-Making MeSH
• Organ Sparing Treatments methods   MeSH
• Humans MeSH
• Neoplasm Metastasis MeSH
• Rectal Neoplasms * surgery   diagnostic imaging   complications   therapy   MeSH
• Neoadjuvant Therapy methods   MeSH
• Watchful Waiting * methods   MeSH
• Recurrence MeSH
• Risk MeSH
• Statistics as Topic MeSH
• Patient Selection MeSH
• Check Tag
• Humans MeSH
• Publication type
• Review MeSH

OBJECTIVE: Pulmonary involvement in chronic nonbacterial osteomyelitis (CNO) is rare. Limited awareness results in diagnostic challenges, especially because malignancy or infection needs to be considered. METHODS: Based on a survey shared among centers participating in the Kerndokumentation Deutsches Rheumaforschungszentrum (Germany), this study investigated clinical and imaging presentations, demographic features, treatment response and outcomes of pulmonary involvement in CNO (pCNO). Magnetic resonance imaging and computed tomography images were read centrally by an experienced pediatric radiologist. RESULTS: Twenty-two patients with pCNO were included in this study. Among patients with CNO, pulmonary involvement was more common in girls (91% vs 62.8%, P = 0.006) and patients with multifocal bone lesions (95% vs 65%, P <0.001) but was not associated with systemic inflammation or additional organ involvement. Forty-two pulmonary lesions were counted with a median of two per patient (two to six). They displayed a median size of 1.8 cm (0.3-4.0 cm) and followed mono- (40%) and oligo-focal (60%) patterns representing consolidations or nodules, abutting the pleura in 50%. Although prominent hilar lymph nodes were present (in 19% of patients), no pathologic enlargement (>1 cm) was seen. When available (3 of 22 patients), histology revealed granulomatous inflammation with lymphocyte infiltration. Development and courses of pCNO did not associate with treatments chosen. Complete remission was reported in 60% of patients, partial remission in 20%. CONCLUSION: pCNO is usually asymptomatic. Although more common in girls and patients with multifocal CNO, pCNO is not associated with systemic parameters of inflammation or specific organ involvement. Prognosis of pCNO is favorable, and most lesions resolve over time. Thus, a careful watch-and-wait strategy may be appropriate.

• Publication type
• Journal Article MeSH

BACKGROUND: Chronic low back pain (CLBP) is one of the most common musculoskeletal problems worldwide. Even though regular exercise is recommended as the primary conservative approach in treating this condition, significant part of patients lead sedentary lifestyle. Motivation to exercise is one of the variables that effects the adherence of exercise-based treatments. This study aimed to characterize the motives for exercise, as posited by self-determination theory, in persons with CLBP, and to identify subgroups (clusters) of motivational profiles in combination with socioeconomic and clinical characteristics using k-means cluster analysis. METHODS: Data were collected between September 2022 and September 2023. A total of 103 adults with CLBP completed the paper-pencil Exercise Self-Regulation Questionnaire (SRQ-E) and provided self-reported measures on anthropometric and socio-economic characteristics. Inclusion criteria were age (≥ 18 years) and non-specific CLBP (lasting longer than 12 weeks). Exclusion criteria included specific lumbar spine pathology (e.g., fracture, cancer), worsening neurological symptoms, recent injection therapy (within 3 months), and current alcohol or drug misuse. RESULTS: Three distinct motivational clusters were identified among the 103 participants: two clusters were characterized by predominantly autonomous motivation (moderately motivated cluster: 31.1%; highly motivated cluster: 54.4%), while one cluster (controlled convinced cluster: 14.6%) showed a higher level of controlled motivation. Associations were observed between the controlled cluster and factors such as higher disability scores, longer duration of pain, greater number of completed physiotherapy sessions, and elevated BMI. Notably, the controlled motivation cluster was linked with poorer clinical outcomes. CONCLUSIONS: This study provides insights into the exercise motivation of patients with CLBP, revealing that while most patients were primarily autonomously motivated, a notable subgroup exhibited lower, controlled motivation. The presence of controlled motivation was associated with worse functioning, longer pain duration, and increased utilization of physiotherapy services. Although these findings suggest a link between motivational profiles and clinical outcomes, the cross-sectional design limits causal inferences. Further research is needed to explore these relationships longitudinally. TRIAL REGISTRATION: ClinicalTrials.Gov Identifier: NCT05512338 (22.8.2022, NCT05512338).

• MeSH
• Chronic Pain * psychology   therapy   rehabilitation   MeSH
• Exercise psychology   MeSH
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Low Back Pain * psychology   therapy   rehabilitation   MeSH
• Motivation * MeSH
• Surveys and Questionnaires MeSH
• Aged MeSH
• Exercise Therapy * methods   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Journal Article MeSH

In less than a decade, immune checkpoint inhibitors (ICIs) have transformed the management of mismatch repair-deficient (dMMR) and microsatellite instability-high (MSI) cancers. However, beyond colorectal cancer (CRC), much of the evidence is mostly derived from non-randomized phase II studies or post-hoc analyses of broader clinical trials. dMMR/MSI tumours represent a specific subgroup of gastro-esophageal adenocarcinomas (GEA), accounting for approximately 9 % of cases, with a higher prevalence in early-stage compared to advanced-stage disease and older female patients. These tumours are predominantly sporadic, often linked to MLH1 promoter methylation, and rarely exhibit HER2 overexpression/ERBB2 amplification or other oncogenic drivers. The treatment landscape for early stage dMMR/MSI GEA is likely to change substantially soon, as ICIs have shown high pathological complete response (pCR) rates in small phase II trials, raising questions on optimisation of neoadjuvant therapy, and paving the way for organ preservation. The standard of treatment for untreated patients with advanced dMMR/MSI GEA is chemotherapy + ICI irrespectively of PDL-1 status. However, the role of chemotherapy-free regimen consisting of CTLA-4 plus PD-1 inhibitors remains undetermined. This review addresses these and other emerging questions, offering expert opinions and insights into the future therapeutic landscape for dMMR/MSI GEA.

• MeSH
• Adenocarcinoma * drug therapy   genetics   pathology   therapy   MeSH
• Immune Checkpoint Inhibitors therapeutic use   MeSH
• Humans MeSH
• Microsatellite Instability * MeSH
• Esophageal Neoplasms * drug therapy   genetics   pathology   MeSH
• Stomach Neoplasms * drug therapy   genetics   pathology   therapy   MeSH
• DNA Mismatch Repair * MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Review MeSH

In response to a recent case report published in the International Journal of Legal Medicine entitled "A case of hemorrhage at the junctions of the posterior intercostal arteries-a vital sign?", we wish to corroborate the findings of periadventitial hemorrhages at the junctions of the posterior intercostal arteries in cases of suicidal hanging and to reveal two other novel aortic lesions associated with hanging. In our ongoing prospective study, we identified six cases of aortic intimal ruptures among 257 suicidal hanging deaths, along with the novel observation of subintimal hemorrhages-both of which have not been previously documented in the forensic literature. Our findings suggest that the complex anatomy of the aorta and surrounding structures may increase the vulnerability of vascular structures during hanging, particularly under conditions of complete suspension. We propose that reported aortic lesions may serve as significant morphological indicators of hanging, thereby enriching its medicolegal investigation. To establish the diagnostic relevance of these findings, further prospective autopsy studies with larger sample sizes are warranted.

• MeSH
• Aorta * pathology   injuries   MeSH
• Asphyxia * pathology   MeSH
• Suicide, Completed * MeSH
• Adult MeSH
• Hemorrhage * pathology   MeSH
• Middle Aged MeSH
• Humans MeSH
• Neck Injuries * pathology   MeSH
• Prospective Studies MeSH
• Aortic Rupture * pathology   MeSH
• Aged MeSH
• Forensic Pathology MeSH
• Tunica Intima pathology   injuries   MeSH
• Check Tag
• Adult MeSH
• Middle Aged MeSH
• Humans MeSH
• Male MeSH
• Aged MeSH
• Female MeSH
• Publication type
• Letter MeSH
• Case Reports MeSH

BACKGROUND AND OBJECTIVE: Given the uncertainty regarding the role of radical nephroureterectomy (RNU) as part of a multimodal treatment strategy for upper tract urothelial carcinoma (UTUC) patients with cN+ disease, we aimed to perform a systematic review and meta-analysis of the corresponding literature. METHODS: Using the Preferred Reporting Items for Systematic Reviews and Meta-analyses guidelines, we identified 17 observational comparative and noncomparative studies, published between January 2000 and September 2024, evaluating UTUC patients with cTanyN+M0 disease (P) who received RNU as part of a multimodal treatment strategy (I), as compared with any treatment strategy if applicable (C), to assess oncological or postoperative outcomes (O). Meta-analyses were further performed, as appropriate. KEY FINDINGS AND LIMITATIONS: Overall, 15 studies evaluated the effectiveness of adding chemotherapy to RNU in the perioperative setting without specifying the exact timing of delivery (n = 1), in the induction setting (n = 14), or in the adjuvant setting (n = 5), while two studies evaluated the effectiveness of adding RNU to chemotherapy. Meta-analyses showed that the use of induction chemotherapy plus RNU versus RNU alone was associated with greater odds of pathological downstaging (risk ratio [RR] = 3.06; 95% confidence interval [CI] = [2.48-3.77]; p < 0.001; I2 = 0%; p = 0.44) and pathological complete nodal response (RR = 2.80; 95% CI = [2.03-3.86]; p < 0.001; I2 = 0%; p = 0.47) as well as prolonged overall survival (HR = 0.52; 95% CI = [0.42-0.64]; p < 0.001; I2 = 14%; p = 0.33) without any significant impact on the risk of overall (RR = 1.14; 95% CI = [0.79-1.64]; p = 0.48; I2 = 0%; p = 0.76) and major (RR = 0.48; 95% CI = [0.18-1.24]; p = 0.13; I2 = 0%; p = 0.87) postoperative complications. In addition, the use of induction chemotherapy plus RNU versus RNU plus adjuvant chemotherapy (HR = 0.58; 95% CI = [0.38-0.89]; p = 0.01) or chemotherapy alone (HR = 0.49; 95% CI = [0.32-0.76]; p = 0.001; I2 = 46%; p = 0.17) was associated with prolonged overall survival. Limitations include the observational design of all included studies. CONCLUSIONS AND CLINICAL IMPLICATIONS: The use of RNU could provide the greatest oncological benefits without any significant harm in selected UTUC patients with fit general condition and resectable cN+ disease responding to induction chemotherapy. PATIENT SUMMARY: In this report, we looked at the outcomes of radical surgery in combination with systemic chemotherapy for upper tract urothelial carcinoma with clinical evidence of dissemination to the surrounding lymph nodes. We observed that the use of radical surgery was associated with the greatest oncological benefits without any increased risk of postoperative complications in patients with fit general condition and resectable disease responding to induction chemotherapy. We conclude that the use of induction chemotherapy plus radical surgery could be the best multimodal treatment strategy for these patients.

• MeSH
• Carcinoma, Transitional Cell * pathology   surgery   therapy   MeSH
• Combined Modality Therapy MeSH
• Humans MeSH
• Lymphatic Metastasis MeSH
• Kidney Neoplasms * pathology   surgery   therapy   MeSH
• Ureteral Neoplasms * pathology   surgery   therapy   MeSH
• Nephroureterectomy * methods   adverse effects   MeSH
• Practice Guidelines as Topic MeSH
• Check Tag
• Humans MeSH
• Publication type
• Journal Article MeSH
• Meta-Analysis MeSH
• Review MeSH
• Systematic Review MeSH