BACKGROUND:Histiocytic diseases are significantly rarer than diseases derived from lymphocytic, plasmacytic, or myeloid lineages, and thus are encountered infrequently in hematology and oncology clinics. The most common form is Langerhans cell histiocytosis, which in adults has an incidence of 1-2 cases per 1 million; the others are considerably rarer, with their occurrence reported only by the number of described cases rather than through incidence or prevalence. Their rarity leads to delays in establishing an accurate diagnosis. OBJECTIVE:The group of histiocytic diseases includes seven clinical units: Langerhans cell histiocytosis, indeterminate dendritic cell histiocytosis, diseases from the juvenile xanthogranuloma group, Erdheim-Chester disease, Rosai-Dorfman disease, ALK-positive histiocytosis, and histiocytic sarcoma. Each of the described diseases has specific manifestations that distinguish it from the manifestations of other malignant blood disorders. The aim of this article is to remind the reader of these manifestations through images and text, thereby contributing to the timely recognition of these rare diseases. CONCLUSION:Treatment procedures are rapidly evolving, but the clinical presentations of these diseases remain unchanged. The disease profiles presented in this publication should aid in their early diagnosis and consequently in timely treatment.

BACKGROUND:Data on the prognostic value of dMMR/MSI-H in locally advancer rectal cancer (LARC) are inconsistent and mostly from patients treated with conventional neoadjuvant therapy. We sought to evaluate oncological outcomes by mismatch repair/microsatellite (MMR/MS) status in LARC patients treated with total neoadjuvant therapy (TNT). METHODS:Patients from the International Real-World Study of TNT in Rectal Cancer tested for dMMR/MSI-H by immunohistochemistry and/or molecular testing were included. Pathological complete response (pCR), complete response (CR, pCR + clinical complete response), event-free survival (EFS) and overall survival (OS) were assessed by MMR/MS status in the overall and matched populations. For the latter, variable-ratio matching according to nine variables (age, year of diagnosis, tumour location, staging modality, cT stage, cN stage, presence of lateropelvic lymphadenopathy, distance from the mesorectal fascia, TNT regimen) was applied. RESULTS:Of 1911 patients, 1320 (69.1%) (09/2012-09/2025) had information on the MMR/MS status, 46 (3.5%) having dMMR/MSI-H tumours. No outcome differences were found by MMR/MS status in the overall population. In the matched population (n = 372), pCR was 14.2% among patients with pMMR/MSS tumours versus 12.5% among those with dMMR/MSI-H tumours (adjusted OR 1.07, 95%CI 0.39-2.91, p = 0.899), while CR was 18.9% and 16.7%, respectively (adjusted OR 0.95, 95%CI 0.35-2.58, p = 0.917). 3-year EFS and 5-year OS were 65.8% and 79.2%, and 67.6% and 93.5% in patients with pMMR/MSS and in those with dMMR/MSI-H tumours, respectively (adjusted HR EFS 1.30, 95%CI 0.57-2.89, p = 0.527; adjusted HR OS 2.52, 95%CI 0.67-9.42, p = 0.171). CONCLUSIONS:In this study, the dMMR/MSI-H phenotype did not hold prognostic value in LARC patients treated with TNT.

In pancreatic ductal adenocarcinoma (PDAC), clinicians often ask whether young age is associated with more aggressive disease or patients more likely to tolerate curative-intent multimodality treatment. The prognostic meaning of age after surgery remains uncertain. We analyzed a retrospective multicenter surgical cohort of patients with resected non-metastatic PDAC. Candidate clinical variables were evaluated in univariable Cox models. The prespecified primary multivariable model included age, sex, N status, T stage, and CA19-9 status. Adjuvant therapy was evaluated in a sensitivity model. The cohort included 696 surgical patients; 70 (10.1%) were aged < 55 years. Median overall survival was 34.4 months in patients aged < 55 years versus 22.0 months in those aged ≥ 55 years (log-rank p = 0.019). In the primary multivariable model, age < 55 years remained independently favorable (HR 0.66, 95% CI 0.49–0.89; p = 0.007). Elevated CA19-9 value independently predicted worse survival (HR 1.39, 95% CI 1.13–1.71; p = 0.002). The sensitivity model confirmed favorable associations for young age and not elevated CA19-9 value. In surgically managed PDAC patients, young age and normal CA19-9 value carried independent favorable prognostic information. Prognosis was also shaped by nodal status, T stage, and receipt of adjuvant therapy.

Pancreatic ductal adenocarcinoma (PDAC) is a malignancy with an exceptionally poor prognosis, characterized by a relatively stable and recurrent spectrum of driver mutations that fail to fully explain the clinical heterogeneity of the disease. In this review, we evaluate alternative splicing (AS) as an additional regulatory layer underlying tumor plasticity and adaptive rewiring. We provide a mechanistically integrated overview of AS dysregulation in PDAC, including the contributions of specialized bioinformatics resources and databases such as TCGASpliceSeq, OncoSplicing, and MAJIQlopedia. We discuss how dysregulation of splicing factors, particularly from the SR and hnRNP protein families, acts as an upstream regulator reprogramming the isoform landscape. Furthermore, we examine how AS deregulation functionally contributes to key hallmarks of malignancy, including apoptosis resistance, metabolic adaptation, and metastatic plasticity. Then, we critically address the methodological aspects of isoform identification and outline future research directions, emphasizing the need for protein-level validation and the translational potential of therapeutic strategies, such as antisense oligonucleotides or spliceosome inhibitors. In conclusion, this review establishes that AS represents a biologically important and potentially therapeutically exploitable dimension of PDAC molecular biology, extending classical genetic models of tumor pathogenesis.

693 Background: Platinum-based chemotherapy followed by avelumab 1L maintenance treatment for patients with nonprogressive disease is a standard of care in la/mUC. In the Czech Republic, following EU approval, there is a requirement to provide real-world data for “highly innovative medicinal products” and obtaining reimbursement requires registry creation for data collection. Interim results from a retrospective analysis of a national reimbursement registry for avelumab 1L maintenance treatment in the Czech Republic were reported previously; here, we report longer-term results. Methods: Registry data were collected by the Health Insurance Bureau for patients with la/mUC receiving avelumab 1L maintenance treatment between Oct 2021 and Jan 2024. The primary endpoint was overall survival (OS) from start of avelumab 1L maintenance (index date); secondary endpoints included progression-free survival (PFS) and safety. Descriptive statistics were used to analyze the data. OS, PFS, and probability of ongoing response were estimated using the Kaplan-Meier method. Results: Overall, 107 patients with la/mUC were treated with avelumab 1L maintenance (77 male/30 female). 1L platinum-based chemotherapy was cisplatin based in 55 patients (51.4%) and carboplatin based in 46 patients (43.0%); 6 patients (5.6%) switched regimens. At the start of avelumab, median age was 72 years (range, 45-92), and 41 patients (38.3%) had visceral metastases. Median follow-up was 8.2 months (range, 0-26.2). Median duration of avelumab treatment was 9.7 months (range, 1.0-29.2). The table shows effectiveness data for avelumab 1L maintenance. Overall, 16 adverse events were reported in 18 patients (16.8%), including 1 patient with a grade 3 infusion reaction and 2 patients with grade 2 diarrhea. At data cutoff (Jan 31, 2024), 88 patients were alive, and 23 had started subsequent treatment. Conclusions: These updated data are generally consistent with results from the JAVELIN Bladder 100 phase 3 trial and other real-world studies, supporting the effectiveness and favorable safety profile of avelumab as 1L maintenance treatment in patients with la/mUC that has not progressed with 1L platinum-based chemotherapy. N=107 Median OS, months Not reached OS rate, % (95% CI) 6 months12 months18 months 93.4 (88.4-98.7)79.3 (69.8-90.2)68.0 (54.6-84.6) Median PFS, months (95% CI) 11.0 (8.6-not estimable) PFS rate, % (95% CI) 6 months12 months18 months 67.8 (58.7-78.2)48.9 (38.8-61.6)39.1 (27.5-55.4) Objective response rate, n (%) Complete response Partial response 29 (27.1)12 (11.2)17 (15.9) Median duration of response, months Not reached Probability of ongoing response, % (95% CI) 6 months12 months18 months 91.1 (80.0-100)80.4 (64.7-99.8)80.4 (64.7-99.8) Median time to response, months 3.4 (1.8-18.2)

Artificial intelligence (AI) and machine learning (ML) are rapidly advancing fields within computer science, driving significant progress in cancer diagnostics. Various ML models have been developed to assist diagnosis, guide therapy decisions, and facilitate early disease detection. In this review, we discuss diverse AI and ML approaches and critically evaluate their applications and limitations in pancreatic cancer histopathology, diagnostics, and biomarker discovery.

Biliary drainage is then one of the necessary procedures to help patients suffering from icterus to reduce serum bilirubin levels and relieve symptoms. The aim of this study was identifying risk factors for survival in patients with cholangiocarcinoma (CCA) treated with percutaneous transhepatic biliary drainage (PTBD) and to develop a simple scoring system predicting survival from PTBD insertion. This single-centre retrospective study included 175 consecutive patients undergoing PTBD for extrahepatic CCA (perihilar and distal). Prognostic factors affecting survival of patients with CCA treated with PTBD were analysed. A multivariate analysis showed that mass forming tumor with mass larger than 5 cm and presence of metastasis at the time of PTBD served as a negative prognostic factor (p = 0.002), better survival was associated with lower preprocedural bilirubin and lower CRP (p = 0.003). Multivariate analysis identified two significant risk factors for 3-month mortality: mass-forming tumors and bilirubin levels exceeding 185 µmol/L. A simple scoring system was developed to predict 3-month mortality after PTBD in patients with advanced CCA, demonstrating 86.3% negative predictive value and 43.2% positive predictive value.

ABSTRACT:Pancreas is a vital gland of gastrointestinal system with exocrine and endocrine secretory functions, interweaved into essential metabolic circuitries of the human body. Pancreatic ductal adenocarcinoma (PDAC) represents one of the most lethal malignancies, with a 5-year survival rate of 11%. This poor prognosis is primarily attributed to the absence of early symptoms, rapid metastatic dissemination, and the limited efficacy of current therapeutic interventions. Despite recent advancements in understanding the etiopathogenesis and treatment of PDAC, there remains a pressing need for improved individualized models, identification of novel molecular targets, and development of unbiased predictors of disease progression. Here we aim to explore the concept of precision medicine utilizing 3-dimensional, patient-specific cellular models of pancreatic tumors and discuss their potential applications in uncovering novel druggable molecular targets and predicting clinical parameters for individual patients.

ABSTRACT Background Molecular tumor boards (MTBs) support the development of personalized treatment strategies for patients with various cancer types based on comprehensive genomic profiling (CGP) of tumor tissue. Despite the unprecedented results demonstrated in many molecularly driven clinical trials, access to matched therapy remains a significant challenge in routine clinical practice worldwide. Methods In this study, we analyzed the MTB cohort from University Hospital Brno in the Czech Republic. Between February 2021 and April 2025, a total of 553 cancer patients with limited therapeutic options underwent CGP of tumor tissue and were subsequently presented at the MTB. Results The median age of the patients was 61.1 years, and 62.2% were female. The most frequently tested diagnoses were colorectal cancer (n = 88; 15.9%), cholangiocarcinoma (n = 66; 11.9%), and pancreatic cancer (n = 65; 11.8%). The median number of prior lines of standard systemic therapy before CGP testing was two. MTB‐recommended matched therapy for 326 (59.0%) out of 553 tested patients, based on 545 unique molecular alterations. The most frequently recommended drugs included immunotherapy (162/545; 29.7%), tyrosine kinase inhibitors (140/545; 25.7%), and poly (ADP‐ribose) polymerase inhibitors (63/545; 11.6%). Reimbursement was requested from healthcare insurance providers in 115 cases, with 87 (75.7%) approvals. Together with other reimbursement forms, a total of 96 (17.4%) out of 553 patients initiated matched therapy. A progression‐free survival ratio (PFS2/PFS1) of ≥ 1.3 was observed in 29 (41.4%) of the 70 evaluable pretreated patients. Conclusion This is the first study to report on a real‐world MTB cohort from the Czech Republic, demonstrating a diagnostic yield comparable to previously published studies, good availability of recommended drugs, and clinical benefit in evaluable patients.

Importance:This was a clinical study of total neoadjuvant therapy (TNT) for rectal cancer. Objective:To assess the use and outcomes of TNT in routine practice. Design, Setting, and Participants:This international, multicenter study was conducted at 61 centers across 21 countries and included consecutive patients treated off trial with TNT for stage II/III rectal adenocarcinoma from September 2012 to December 2023. Data were analyzed between August and October 2024. Exposure:TNT, defined as the delivery of radiotherapy and nonradiosensitizing chemotherapy before surgery or watch and wait. Main Outcomes and Measures:The primary outcome was type of TNT administered. Secondary outcomes were patient characteristics, treatment adherence, safety, and efficacy overall and by type of TNT in the entire population and after propensity vector matching. Results:A total of 1585 patients (588 female [37.1%]; median [IQR] age, 61 [53-68] years) were included, 1260 (79.5%) of whom had 1 or more high-risk features (eg, cT4, cN2, extramural venous invasion, threatened/involved mesorectal fascia, and lateropelvic lymphadenopathy). Patients were treated with the PRODIGE 23-like regimen (FOLFIRINOX/FOLFOXIRI followed by long-course chemoradiotherapy) (271 [17.7%]), RAPIDO-like regimen (short-course radiotherapy followed by consolidation FOLFOX/CAPOX) (529 [33.4%]), OPRA induction-like (induction FOLFOX/CAPOX followed by long-course chemoradiotherapy) (190 [12.0%]), OPRA consolidation-like (long-course chemoradiotherapy followed by consolidation FOLFOX/CAPOX) (257 [16.2%]), and other regimens (360 [22.7%]). After TNT, 192 (12.1%) underwent watch and wait, and 30 (1.9%) underwent local excision. Pathological or clinical complete response was reported in 23.2% of cases. At treatment failure, 8.5% was local and 16.4% was distant progression. Three-year event-free survival (EFS) was 68% (95% CI, 64%-71%), and 5-year overall survival (OS) was 79% (95% CI, 75%-83%). In the overall population, patients treated with the PRODIGE 23-like regimen were most likely to have serious adverse events (61 [23.5%]) but had better local control and survival outcomes than those treated with the RAPIDO-like (EFS: hazard ratio [HR], 0.68; 95% CI, 0.49-0.95; P = .03; OS: HR, 0.51; 95% CI, 0.27-0.97; P = .04), OPRA induction-like (EFS: HR, 0.66; 95% CI, 0.44-0.98; P = .04; OS: HR, 0.35; 95% CI, 0.18-0.70; P = .003), and OPRA consolidation-like (EFS: HR, 0.64; 95% CI, 0.44-0.93; P = .02; OS: HR, 0.50; 95% CI, 0.25-1.00; P = .05) regimens. In the matched population (928 patients [58.5%]), no differences in survival outcomes were observed between the TNT regimens. Conclusions and Relevance:The findings of this case series study show substantial variation in the choice of the TNT regimen and were overall aligned with those reported in clinical trials, suggesting the efficacy of TNT in a clinical setting regardless of the specific regimen.

Multidisciplinary molecular tumor boards (MTB) are already well established in many comprehensive cancer centers and play an important role in the individual treatment planning for cancer patients. Comprehensive genomic profiling of tumor tissue based on next-generation sequencing is currently performed for diagnostic and mainly predictive testing. If somatic genomic variants are identified, which are suspected to be pathogenic germline variants (PGVs), MTB propose genetic counseling and germline DNA testing. Commonly used comprehensive genomic profiling approaches of tumor tissue do not include a matched germline DNA control. Therefore, the detection of PGVs could be only predicted based on the content of tumor cells (CTC) in selected tumor area (%) and variant allele frequency score (%). For conclusion, the role of a medical geneticist is essential in these cases. The overall prevalence of PGVs in patients with pancreatic ductal adenocarcinoma (PDAC) and colorectal cancer (CRC) is approximately 10%. In this single-center study, we present 37 patients with PDAC and 48 patients with CRC who were presented at MTB and tested using the large combined DNA/RNA sequencing panel. Content of tumor cells and variant allele frequency scores were evaluated in all tested patients. In case of suspicion of PGV and no previous genetic testing based on the standard guidelines, genetic counseling was recommended regardless of age, sex, and family history. In the PDAC subgroup, five patients were recommended by MTB for genetic counseling based on suspicious genetic findings. Based on a medical geneticist's decision, germline DNA sequencing was performed in four of these cases, and all of them tested positive for PGV in the following genes: ATM, ATM, BRCA1, and BRCA2. In the CRC subgroup, no PGV was confirmed in the two patients genetically tested based on the MTB recommendations. Furthermore, we present data from our center's registry of patients with PDAC and CRC who underwent genetic counseling and germline DNA testing based on the standard screening criteria. Our data confirm that comprehensive genomic profiling of tumor tissue can identify patients with hereditary forms of PDAC, who could remain unidentified by standard screening for hereditary forms of cancer.

The incidence of pancreatic cancer (pancreatic ductal adenocarcinoma - PDAC) is increasing, especially in developed countries. In 2021, 496,000 new PDAC cases were dia-gnosed worldwide. In the Czech Republic, the incidence is one of the highest in the world, with 2,332 new PDAC patients dia-gnosed in 2018. Due to the absence of symptoms in the early stages, approximately 50% of patients are initially dia-gnosed with distant metastases. Mortality is slightly lower than the incidence count and, despite significant advances in cancer research, PDAC remains a fatal dia-gnosis. However, microbio-me seems to be an interesting approach, and not only in PDAC patients. Microbio-me is defined as the set of all microorganisms (microbio-ta, i.e. bacteria, fungi, viruses, archaea, and protozoa) and their genome in a certain environment. In a physiological setting, the gut microbio-me is in symbio-sis with the host organism, maintaining the balance of metabolism, mucosal immunomodulation and regulating the digestion process. When dysregulation of the number or function of intestinal microorganisms occurs, dysbio-sis is developed. It may lead to metabolic and cardiovascular diseases, nervous system disorders, induction of intestinal inflammation, or carcinogenesis. Microbio-ta can induce carcinogenesis in multiple ways, such as by activating an inflammatory response, reducing the immune system's ability to eliminate damaged cells, and deregulation of the host genome by microbial metabolites. This deregulation may lead to an activation of pro-apoptotic and pro-proliferative proteins. To date, research shows that the gut or oral microbio-me may be involved in the development of PDAC. One of the most studied bacteria is Porphyromonas gingivalis. Other bacteria, such as Fusobacteria, Enterobacter, Klebsiella, Prevotella, and Rothia, have also been shown to play a role in PDAC.

Introduction/Background The program of the applied precision oncology approach using combined genomic and immunohistochemical (IHC) analyses to develop individual treatment plans in adult patients (pts) with solid tumors has been established in University Hospital Brno since March 2021. We hereby report the results achieved in patients with gynecological tumors. Methodology Patients undergoing systemic treatment with palliative intent are referred to Molecular Tumor Board (MTB). Whenever possible, the molecular analyses using next-gene sequencing (NGS) together with IHC analyses of key potential targets as requested by the referring physician are performed. The patients whose tumors show an aberration are treated with matched targeted therapy proposed by MTB, when available. Results Between March 2021 and April 2023, 76 pts with gynecological tumors were referred to MTB; 45 (59%) with ovarian cancer, 15 (20%) uterine cancer, 11 (14%) cervical cancer, 4 (5%) with vaginal/vulvar cancer and 1 (1%) with both ovarian and uterine cancer. Median age at the time of profiling was 59 years, median time from the tumor sampling to profiling was 17 months. Results of profiling were available for 68 tumors with actionable aberrations detected in 49 samples (72%). Based on NGS, actionable genomic signature was found in 13/68 tumors (19%) and gene alterations with targeted therapy available in 30/68 tumors (44%). In total, only 2 samples (3%) did not meet the quality criteria for NGS. By IHC, PDL1 positivity (≥1 either by TPS or CPS) was detected in 32/58 examined tumors (57%), MMR-deficiency in 5/56 tumors (9%) and HER-2 positivity in 2/19 tumors (11%). So far, proposed matched therapy has been started in 16/49 patients (33%) with median time of duration 74.5 days compared to 63.5 days within the prior line of treatment. Conclusion Combined genomic and immunohistochemical profiling of gynecological tumors is an efficient approach to match patients with targeted therapy. Disclosures This research was funded by the Ministry of Health of the Czech Republic (MHCR), grant number NU21–03-00306, and MHCR-Development of Research Organization (FNBr, 65269705).

Extragonadální nádory ze zárodečných buněk jsou vzácná, ale často agresivní onemocnění, která vyžadují časnou diagnostiku a intenzivní terapii. Do této skupiny patří i extragonadální choriokarcinom, který je spojován především s ženským pohlavím v období gestace, může se však vyskytovat i u mužů. V naší kazuistice popisujeme případ mladého pacienta s "high-volume" metastatickým extragonadálním choriokarcinomem, který i přes život ohrožující komplikace po intenzivní terapii dosáhl celkové remise onemocnění.

Pheochromocytomas (PCCs) are rare neuroendocrine tumors derived from the chromaffin cells of the adrenal medulla. When these tumors have an extra-adrenal location, they are called paragangliomas (PGLs) and arise from sympathetic and parasympathetic ganglia, particularly of the para-aortic location. Up to 25% of PCCs/PGLs are associated with inherited genetic disorders. The majority of PCCs/PGLs exhibit indolent behavior. However, according to their affiliation to molecular clusters based on underlying genetic aberrations, their tumorigenesis, location, clinical symptomatology, and potential to metastasize are heterogenous. Thus, PCCs/PGLs are often associated with diagnostic difficulties. In recent years, extensive research revealed a broad genetic background and multiple signaling pathways leading to tumor development. Along with this, the diagnostic and therapeutic options were also expanded. In this review, we focus on the current knowledge and recent advancements in the diagnosis and treatment of PCCs/PGLs with respect to the underlying gene alterations while also discussing future perspectives in this field.

Pancreatic ductal adenocarcinoma (PDAC) is a dreaded malignancy with a dismal 5-year survival rate despite maximal efforts on optimizing treatment strategies. Currently, early detection is considered to be the most effective way to improve survival as radical resection is the only potential cure. PDAC is often divided into four categories based on the extent of disease: resectable, borderline resectable, locally advanced, and metastatic. Unfortunately, the majority of patients are diagnosed with locally advanced or metastatic disease, which renders them ineligible for curative resection. This is mainly due to the lack of or vague symptoms while the disease is still localized, although appropriate utilization and prompt availability of adequate diagnostic tools is also critical given the aggressive nature of the disease. A cost-effective biomarker with high specificity and sensitivity allowing early detection of PDAC without the need for advanced or invasive methods is still not available. This leaves the diagnosis dependent on radiodiagnostic methods or endoscopic ultrasound. Here we summarize the latest epidemiological data, risk factors, clinical manifestation, and current diagnostic trends and implications of PDAC focusing on serum biomarkers and imaging modalities. Additionally, up-to-date management and therapeutic algorithms are outlined.

The presence of activating somatic mutations in the KRAS and NRAS oncogenes is a negative predictor of treatment with the anti-epidermal growth factor receptor (EGFR) monoclonal antibody in colorectal cancer. The BRAF oncogene also plays an important role in carcinogenesis, and, in colorectal cancer, is associated with an unfavorable prognosis. Mutations in RAS and BRAF are usually considered mutually exclusive. Concomitant mutations present in these oncogenes are rare. However, according to recent analyzes, the incidence of concomitant RAS and BRAF mutations in colorectal cancer may be higher than it is currently expected. In the presented case report of a 44-year-old woman treated for metastatic rectal cancer with concomitant KRAS and BRAF mutations in primary tumor and wild-type KRAS status in metastases, we demonstrated improved survival outcome and quality of life after treatment with BRAF inhibitor encorafenib and the anti-EGFR monoclonal antibody cetuximab.Patient Consent Statement: Written informed consent was obtained from the patient's family for the publication of this report.

Pancreatic cancer is the third leading cause of cancer death in the developed world and is predicted to become the second by 2030. A cure may be achieved only with surgical resection of an early diagnosed disease. Surgery for more advanced disease is challenging and can be contraindicated for many reasons. Neoadjuvant therapy may improve the probability of achieving R0 resection. It consists of systemic treatment followed by radiation therapy applied concurrently or sequentially with cytostatics. A novel approach to irradiation, stereotactic body radiotherapy (SBRT), has the potential to improve treatment results. SBRT can deliver higher doses of radiation to the tumor in only a few treatment fractions. It has attracted significant interest for pancreatic cancer patients, as it is completed quickly, requires less time away from full-dose chemotherapy, and is well-tolerated than conventional radiotherapy. In this review, we aim to provide the reader with a basic overview of current evidence for SBRT indications in the treatment of pancreatic tumors. In the second part of the review, we focus on practical information with respect to SBRT treatment plan preparation the performance of such therapy. Finally, we discuss future directions related to the use of magnetic resonance linear accelerators.