The Peptidoglycan Recognition Protein 1 confers immune evasive properties on pancreatic cancer stem cells.

OBJECTIVE: Pancreatic ductal adenocarcinoma (PDAC) has limited therapeutic options, particularly with immune checkpoint inhibitors. Highly chemoresistant 'stem-like' cells, known as cancer stem cells (CSCs), are implicated in PDAC aggressiveness. Thus, comprehending how this subset of cells evades the immune system is crucial for advancing novel therapies. DESIGN: We used the KPC mouse model (LSL-KrasG12D/+; LSL-Trp53R172H/+; Pdx-1-Cre) and primary tumour cell lines to investigate putative CSC populations. Transcriptomic analyses were conducted to pinpoint new genes involved in immune evasion. Overexpressing and knockout cell lines were established with lentiviral vectors. Subsequent in vitro coculture assays, in vivo mouse and zebrafish tumorigenesis studies, and in silico database approaches were performed. RESULTS: Using the KPC mouse model, we functionally confirmed a population of cells marked by EpCAM, Sca-1 and CD133 as authentic CSCs and investigated their transcriptional profile. Immune evasion signatures/genes, notably the gene peptidoglycan recognition protein 1 (PGLYRP1), were significantly overexpressed in these CSCs. Modulating PGLYRP1 impacted CSC immune evasion, affecting their resistance to macrophage-mediated and T-cell-mediated killing and their tumourigenesis in immunocompetent mice. Mechanistically, tumour necrosis factor alpha (TNFα)-regulated PGLYRP1 expression interferes with the immune tumour microenvironment (TME) landscape, promoting myeloid cell-derived immunosuppression and activated T-cell death. Importantly, these findings were not only replicated in human models, but clinically, secreted PGLYRP1 levels were significantly elevated in patients with PDAC. CONCLUSIONS: This study establishes PGLYRP1 as a novel CSC-associated marker crucial for immune evasion, particularly against macrophage phagocytosis and T-cell killing, presenting it as a promising target for PDAC immunotherapy.

Stereotactic body radiotherapy in pancreatic adenocarcinoma.

BACKGROUND: Stereotactic body radiotherapy (SBRT) in pancreatic cancer allows high delivery of radiation doses on tumors without affecting surrounding tissue. This review aimed at the SBRT application in the treatment of pancreatic cancer. DATA SOURCES: We retrieved articles published in MEDLINE/PubMed from January 2017 to December 2022. Keywords used in the search included: "pancreatic adenocarcinoma" OR "pancreatic cancer" AND "stereotactic ablative radiotherapy (SABR)" OR "stereotactic body radiotherapy (SBRT)" OR "chemoradiotherapy (CRT)". English language articles with information on technical characteristics, doses and fractionation, indications, recurrence patterns, local control and toxicities of SBRT in pancreatic tumors were included. All articles were assessed for validity and relevant content. RESULTS: Optimal doses and fractionation have not yet been defined. However, SBRT could be the standard treatment in patients with pancreatic adenocarcinoma in addition to CRT. Furthermore, the combination of SBRT with chemotherapy may have additive or synergic effect on pancreatic adenocarcinoma. CONCLUSIONS: SBRT is an effective modality for patients with pancreatic cancer, supported by clinical practice guidelines as it has demonstrated good tolerance and good disease control. SBRT opens a possibility of improving outcomes for these patients, both in neoadjuvant treatment and with radical intent.

Current landscape of gastrointestinal radiation oncology in Spain: a multicenter real-life survey and comparison with key clinical guidelines.

Background: The GI Tumors Workgroup, a division of the Spanish Society of Radiation Therapy, conducted a survey in December 2020 to assess the adherence of radiation oncologists in Spain to international guidelines for gastrointestinal tumors. Materials and methods: Using Google Forms, we designed a survey covering treatments for esophageal, gastric, pancreatic, and rectal cancers. Results: In esophageal cancer treatment, neoadjuvant chemoradiation was the standard in 76.7% of institutions. Radiation doses range from 41.1 to 50.4 Gy in conventional fractionation. Planning positron emission tomography-computed tomography (PET-CT) was performed in 83.3% of centers, and intensity-modulated radiation therapy/volumetric-arc radiation therapy (IMRT/VMAT) was the preferred technique in 86.7% of institutions. For gastric cancer, 71.4% followed perioperative chemotherapy guidelines. In the case of adjuvant radiotherapy, the majority prescribed 45-50.4 Gy, and 82.1% used IMRT/VMAT for treatment. For pancreas cancer, neoadjuvant chemotherapy followed by surgery in borderline resectable tumors and induction chemotherapy followed by radical radiotherapy for non-resectable tumors were the most frequent approaches. IMRT/VMAT was the primary technique. Locally advanced rectal cancer treatment is mainly based on neoadjuvant radiotherapy in all institutions. The preferred radiation doses typically range from 45 to 50 Gy in conventional fractionation. IMRT/VMAT was standard in most Institutions. Conclusions: Spain's radiotherapy practices among respondents generally align with international guidelines for GI tumors highlighting Spain's commitment to evidence-based medical practice.

SARS-CoV-2 Virus in Cancer Patients: A New Unknown in an Unsolved Equation.

INTRODUCTION: Cancer patients are more susceptible to infections, and infection can be more severe than in patients without cancer diagnosis. We conducted this retrospective study in patients admitted for SARS-CoV-2 infection in order to find differences in inflammatory markers and mortality in cancer patients compared to others. METHODS: We reviewed the electronic records of patients admitted for SARS-CoV-2 infection confirmed by PCR from March to September 2020. Data on socio-demographics, comorbidities, inflammatory makers, and cancer-related features were analyzed. RESULTS: 2,772 patients were admitted for SARS-CoV-2, to the Hospital Universitario Ramón y Cajal in Madrid during this period. Of these, 2,527 (91%) had no history of neoplastic disease, 164 (5.9%) patients had a prior history of cancer but were not undergoing oncological treatment at the time of infection, and 81 (2.9%) were in active treatment. Mortality in patients without a history of cancer was 19.5%, 28.6% for patients with a prior history of cancer, and 34% in patients with active cancer treatment. Patients in active oncology treatment with the highest mortality rate were those diagnosed with lung cancer (OR 5.6 95% CI: 2.2-14.1). In the multivariate study, active oncological treatment (OR 2.259 95% CI: 1.35-3.77) and chemotherapy treatment (OR 3.624 95% CI: 1.17-11.17), were statistically significant factors for the risk of death for the whole group and for the group with active oncological treatment, respectively. CONCLUSION: Cancer patients on active systemic treatment have an increased risk of mortality after SARS-CoV-2 infection, especially with lung cancer or chemotherapy treatment.

The Diet as a Modulator of Tumor Microenvironment in Colorectal Cancer Patients.

Colorectal cancer (CRC) is one of the most common cancers in Western countries and remains the second most common cause of cancer death worldwide. Many studies show the importance of diet and lifestyle in the incidence of CRC, as well as in CRC prevention. However, this review summarizes those studies that analyze the impact of nutrition on tumor microenvironment modulation and cancer progression. We review the available information about the effects of specific nutrients on cancer cell progression and on the different cells within the tumor microenvironment. Diet and nutritional status in the clinical management of colorectal cancer patients are also analyzed. Finally, future perspectives and challenges are discussed, with a view to improving CRC treatments by employing nutritional approaches. These promise great benefits and will eventually improve CRC patients' survival.

Radiomics in pancreatic cancer for oncologist: Present and future.

Radiomics is changing the world of medicine and more specifically the world of oncology. Early diagnosis and treatment improve the prognosis of patients with cancer. After treatment, the evaluation of the response will determine future treatments. In oncology, every change in treatment means a loss of therapeutic options and this is key in pancreatic cancer. Radiomics has been developed in oncology in the early diagnosis and differential diagnosis of benign and malignant lesions, in the evaluation of response, in the prediction of possible side effects, marking the risk of recurrence, survival and prognosis of the disease. Some studies have validated its use to differentiate normal tissues from tumor tissues with high sensitivity and specificity, and to differentiate cystic lesions and pancreatic neuroendocrine tumor grades with texture parameters. In addition, these parameters have been related to survival in patients with pancreatic cancer and to response to radiotherapy and chemotherapy. This review aimed to establish the current status of the use of radiomics in pancreatic cancer and future perspectives.

Radiotherapy in Prostate Brain Metastases: A Review of the Literature.

Brain metastases in prostate cancer are infrequent. Treatment of brain metastases includes radiotherapy. The aim of this literature review was to study whole brain radiotherapy, radiosurgery, and fractionated stereotactic radiotherapy and its applications in the treatment of prostate brain metastasis. We searched MEDLINE and PUBMED for articles published in the last 5 years and identified 153 articles. After examining them, 31 articles met the selection criteria and were included. Most were retrospective studies. MeSH terms used in the search included: prostate cancer OR prostate brain metastases AND radiotherapy, brain metastases AND radiotherapy AND prostate cancer. English language articles with information on the type of radiotherapy, doses and fractionation, indications, local control, toxicities, and survival of radiotherapy in prostate brain metastasis were included in this review. All articles were assessed for validity and relevant content. The usual treatment of prostate brain metastasis involves whole brain radiotherapy; however, the current trend in the metastases of prostate cancer and of other origins is the use of radiosurgery techniques or stereotactic body radiotherapy.

Interobserver Variability in Contouring Hepatocellular Carcinoma at a Tertiary Center.

BACKGROUND/AIM: The optimal imaging test for delineation of the gross tumor volume (GTV) in hepatocellular carcinoma has not been defined. The hypothesis is that magnetic resonance imaging (MRI) allows for better visualization of the extent of tumor and will optimize the accuracy of tumor delineation for liver stereotactic radiotherapy compared with computed tomography (CT) only. We evaluated the interobserver agreement in GTV of hepatocellular carcinoma in a multicenter panel and compared MRI and CT in GTV delineation. MATERIALS AND METHODS: After the institutional review boards approved the study, we analyzed anonymous CT and MRI obtained from five patients with hepatocellular carcinoma. Eight radiation oncologists at our center used CT and MRI to delineate five GTVs of liver tumors. In both CT and MRI, the GTV volumes were compared. RESULTS: The median GTV volume on MRI was 2.4 cm3 (range=0.59-15.6 cm3) compared to 3.5 cm3 (range=0.52-24.9 cm3) on CT (p=0.36). The GTV volume as defined on MRI was larger or at least as large as the GTV volume on CT in two cases. Variance and standard deviation between observers in CT and MRI were minor (6 vs. 7.87 cm3, and 2.5 vs. 2.8 cm3 respectively). CONCLUSION: In cases with well-defined tumors, CT is easier and reproducible. In cases with no defined tumor in CT, other tools are needed and MRI can be complementary. The interobserver variability in target delineation of hepatocellular carcinoma in this study is noteworthy.

Establishment of Pancreatic Cancer-Derived Tumor Organoids and Fibroblasts From Fresh Tissue.

Tumor organoids are three-dimensional (3D) ex vivo tumor models that recapitulate the biological key features of the original primary tumor tissues. Patient-derived tumor organoids have been used in translational cancer research and can be applied to assess treatment sensitivity and resistance, cell-cell interactions, and tumor cell interactions with the tumor microenvironment. Tumor organoids are complex culture systems that require advanced cell culture techniques and culture media with specific growth factor cocktails and a biological basement membrane that mimics the extracellular environment. The ability to establish primary tumor cultures highly depends on the tissue of origin, the cellularity, and the clinical features of the tumor, such as the tumor grade. Furthermore, tissue sample collection, material quality and quantity, as well as correct biobanking and storage are crucial elements of this procedure. The technical capabilities of the laboratory are also crucial factors to consider. Here, we report a validated SOP/protocol that is technically and economically feasible for the culture of ex vivo tumor organoids from fresh tissue samples of pancreatic adenocarcinoma origin, either from fresh primary resected patient donor tissue or patient-derived xenografts (PDX). The technique described herein can be performed in laboratories with basic tissue culture and mouse facilities and is tailored for wide application in the translational oncology field.

SBRT in Localized Renal Carcinoma: A Review of the Literature.

Stereotactic body radiotherapy (SBRT) allows high doses of radiation to be administered in a limited number of fractions. The high doses per session might allow the theoretical radioresistance of renal carcinoma to be overcome. SBRT may be a therapeutic alternative in inoperable patients with localized renal carcinoma. This review studied the available literature on the use of SBRT in inoperable localized renal carcinoma. The review including data from English-language studies was conducted in PubMed and MEDLINE between January 2010 and December 2020. Articles were included with data from patients with renal carcinoma treated with SBRT, their indications, simulation, dose and fractionation, local control, survival and side effects, comparison with other treatments, response assessment and radioimmunotherapy. The articles included were evaluated for content and validation. The immobilization systems were variable between studies. Doses and fractions were variable from 25-26 Gy in single fractions to 21-48 Gy in 3-5 fractions, with local control being around 90% with a low rate of side-effects. We review the state of the art in SBRT for renal cell carcinoma. More research is needed to determine optimal doses and fractionation, and to develop a reliable response assessment tool. The role of radioimmunotherapy in renal carcinoma is being studied.

Interobserver variability in gross tumor volume contouring in non-spine bone metastases.

Background and Aim: The optimal imaging test for gross tumor volume (GTV) delineation in non-spine bone metastases has not been defined. The use of stereotactic body radiotherapy (SBRT) requires accurate target delineation. Magnetic resonance imaging (MRI) and/or 18fludesoxyglucose positron emission tomography (18FDG-PET) allow for better visualization of the extent of bone metastases and optimizes the accuracy of tumor delineation for stereotactic radiotherapy compared to computed tomography (CT) alone. We evaluated the interobserver agreement in GTV of non-spine bone metastases in a single center and compared MRI and/or 18FDG-PET and CT in GTV delineation. Methods: Anonymous CT and MRI and/or 18FDG-PET obtained from 10 non-spine bone metastases were analyzed by six radiation oncologists at our center. Images acquired by CT and MRI and/or 18FDG-PET were used to delineate 10 GTVs of non-spine bone metastases in the pelvis, extremities, and skull. The cases showed different characteristics: blastic and lytic metastases, and different primary cancers (lung, breast, prostate, rectum, urothelial, and biliary). In both CT and MRI and/or 18FDG-PET, the GTV volumes were compared. The index of agreement was evaluated according to Landis and Koch protocol. Results: The GTV volume as defined on MRI was in all cases larger or at least as large as the GTV volume on CT (P=0.25). The median GTV volume on MRI was 3.15 cc (0.027-70.64 cc) compared to 2.8 cc on CT (0.075-77.95 cc). Interobserver variance and standard deviation were lower in CT than MRI (576.3 vs. 722.2 and 24.0 vs. 26.9, respectively). The level of agreement was fair (kappa=0.36) between CT and MRI. The median GTV volume on 18FDG-PET in five patients was 5.8 cc (0.46-64.17 cc), compared to 4.1 cc on CT (0.99-54.2 cc) (P=0.236). Interobserver variance and standard deviation in CT, MRI, and 18FDG-PET were 576.3 versus 722.2 versus 730.5 and 24 versus 26.9 versus 27.0, respectively. The level of agreement was slight (kappa=0.08) between CT and 18FDG-PET. Conclusions: Interobserver variance in non-spine bone metastases was equal when MRI and PET were compared to CT. CT was associated with the lowest variance and standard deviation. Compared to CT GTVs, the GTVs rendered from MRI images had fair agreement, while the GTVs rendered from 18FDG-PET had only slight agreement. Relevance for Patients: The delimitation of the treatment volume in non-spine bone metastases with SBRT is important for the results determining its efficacy. It is therefore essential to know the variability and to manage it to achieve the highest quality of treatment.

Imaging standardisation in metastatic colorectal cancer: A joint EORTC-ESOI-ESGAR expert consensus recommendation.

BACKGROUND: Treatment monitoring in metastatic colorectal cancer (mCRC) relies on imaging to evaluate the tumour burden. Response Evaluation Criteria in Solid Tumors provide a framework on reporting and interpretation of imaging findings yet offer no guidance on a standardised imaging protocol tailored to patients with mCRC. Imaging protocol heterogeneity remains a challenge for the reproducibility of conventional imaging end-points and is an obstacle for research on novel imaging end-points. PATIENTS AND METHODS: Acknowledging the recently highlighted potential of radiomics and artificial intelligence tools as decision support for patient care in mCRC, a multidisciplinary, international and expert panel of imaging specialists was formed to find consensus on mCRC imaging protocols using the Delphi method. RESULTS: Under the guidance of the European Organisation for Research and Treatment of Cancer (EORTC) Imaging and Gastrointestinal Tract Cancer Groups, the European Society of Oncologic Imaging (ESOI) and the European Society of Gastrointestinal and Abdominal Radiology (ESGAR), the EORTC-ESOI-ESGAR core imaging protocol was identified. CONCLUSION: This consensus protocol attempts to promote standardisation and to diminish variations in patient preparation, scan acquisition and scan reconstruction. We anticipate that this standardisation will increase reproducibility of radiomics and artificial intelligence studies and serve as a catalyst for future research on imaging end-points. For ongoing and future mCRC trials, we encourage principal investigators to support the dissemination of these imaging standards across recruiting centres.

Toward Personalized Medicine in Radiotherapy of Hepatocellular Carcinoma: Emerging Radiomic Biomarker Candidates of Response and Toxicity.

Radiology and radiotherapy are currently undergoing radical transformation with use of biomarkers and digital technologies such as artificial intelligence. These current and upcoming changes in radiology speak of an overarching new vision for personalized medicine. This is particularly evident in the case of radiotherapy of cancers, and of liver cancer in particular. The development of modern radiotherapy with stereotactic body radiotherapy allows targeted treatments to be delivered to the tumor site, limiting the dose to surrounding healthy organs, thus becoming a new therapeutic alternative for hepatocellular carcinoma and other liver tumors. However, not all patients have the same response to radiotherapy or display the same side-effect profile. Biomarkers of response and toxicity in liver radiotherapy would facilitate the vision and practice of personalized medicine. This expert review examines the available molecular, radiomic, and radiogenomic biomarker candidates for acute liver toxicity with potential use for prediction of radiotherapy-induced liver toxicity. To this end, I highlight for oncologists and life scientists that radiomics allows diagnostic images to be analyzed using computer algorithms to extract information imperceptible to the human eye and of relevance to forecasting clinical outcomes. This article underscores particularly (1) the microRNA-based biomarker candidates as among the most promising predictors of radiation-induced liver toxicity and (2) the texture features in radiomic analyses for response prediction. Radiotherapy of hepatocellular carcinoma is edging toward personalized medicine with emerging radiomic biomarker candidates. Future large-scale biomarker studies are called for to enable personalized medicine in liver cancers.

Radiogenomics: Hunting Down Liver Metastasis in Colorectal Cancer Patients.

Radiomics is a developing new discipline that analyzes conventional medical images to extract quantifiable data that can be mined for new biomarkers that show the biology of pathological processes at microscopic levels. These data can be converted into image-based signatures to improve diagnostic, prognostic and predictive accuracy in cancer patients. The combination of radiomics and molecular data, called radiogenomics, has clear implications for cancer patients' management. Though some studies have focused on radiogenomics signatures in hepatocellular carcinoma patients, only a few have examined colorectal cancer metastatic lesions in the liver. Moreover, the need to differentiate between liver lesions is fundamental for accurate diagnosis and treatment. In this review, we summarize the knowledge gained from radiomics and radiogenomics studies in hepatic metastatic colorectal cancer patients and their use in early diagnosis, response assessment and treatment decisions. We also investigate their value as possible prognostic biomarkers. In addition, the great potential of image mining to provide a comprehensive view of liver niche formation is examined thoroughly. Finally, new challenges and current limitations for the early detection of the liver premetastatic niche, based on radiomics and radiogenomics, are also discussed.

GOECP/SEOR radiotherapy guidelines for small-cell lung cancer.

Small cell lung cancer (SCLC) accounts for approximately 20% of all lung cancers. The main treatment is chemotherapy (Ch). However, the addition of radiotherapy significantly improves overall survival (OS) in patients with non-metastatic SCLC and in those with metastatic SCLC who respond to Ch. Prophylactic cranial irradiation reduces the risk of brain metastases and improves OS in both metastatic and non-metastatic patients. The 5-year OS rate in patients with limited-stage disease (non-metastatic) is slightly higher than 30%, but less than 5% in patients with extensive-stage disease (metastatic). The present clinical guidelines were developed by Spanish radiation oncologists on behalf of the Oncologic Group for the Study of Lung Cancer/Spanish Society of Radiation Oncology to provide a current review of the diagnosis, planning, and treatment of SCLC. These guidelines emphasise treatment fields, radiation techniques, fractionation, concomitant treatment, and the optimal timing of Ch and radiotherapy. Finally, we discuss the main indications for reirradiation in local recurrence.

Advances and controversies in the management of early stage non-small cell lung cancer.

Complete resection continues to be the gold standard for the treatment of early-stage lung cancer. The landmark Lung Cancer Study Group trial in 1995 established lobectomy as the minimum intervention necessary for the management of early-stage non-small cell lung cancer, as it was associated with lower recurrence and metastasis rates than sublobar resection and lower postoperative morbidity and mortality than pneumonectomy. There is a growing tendency to perform sublobar resection in selected cases, as, depending on factors such as tumor size, histologic subtype, lymph node involvement, and resection margins, it can produce similar oncological results to lobectomy. Alternative treatments such as stereotactic body radiotherapy and radiofrequency ablation can also produce good outcomes in inoperable patients or patients who refuse surgery.

SBRT in non-spine bone metastases: a literature review.

Stereotactic Body Radiotherapy (SBRT) is a technique for delivering high doses of radiation to tumors while preserving the normal tissues located around this area. Bone metastases are frequent in cancer patients. They can be distressingly painful or may cause pathological fractures. Radiation therapy is a fundamental aspect of treatment for bone metastases. The objective of this study is to analyze the literature on non-spine bone metastasis treated with SBRT, including immobilization, volume delineation, dose and fractionation, local control, side effects, and assessment of response after treatment. Full-text articles written in English language and published in the last 10 years were included in this review and were accessible on PubMed and MEDLINE. We examined 78 articles. A total of 40 studies were included in this review. Most were retrospective studies. The articles included were evaluated for content and validation. The immobilization systems and imaging tests used for tumor delimitation were variable between studies. The use of CTV (Clinical Target Volume) has not been defined. Doses and fractions were variable from 15 to 24 Gy/1 fraction to 24-50 Gy in 3-5 fractions, with local control being around 90% with a low rate of side effects. We review state of the art in SBRT non-spine metastases. SBRT can result in better local control and pain management in non-spine bone metastases patients. We need more research in volume delineation determining whether or not to use CTV and the role of MRI in volume contouring, optimal doses, and fractionation according to histology and a reliable response assessment tool. Studies that compare SBRT to conventional radiotherapy in local control and pain control are needed.

Radiomics in lung cancer for oncologists.

Radiomics has revolutionized the world of medical imaging. The aim of this review is to guide oncologists in radiomics and its applications in diagnosis, prediction of response and damage, prediction of survival, and prognosis in lung cancer. In this review, we analyzed published literature on PubMed and MEDLINE with papers published in the last 10 years. We included papers in English language with information about radiomics features and diagnostic, predictive, and prognosis of radiomics in lung cancer. All citations were evaluated for relevant content and validation. RELEVANCE FOR PATIENTS: The evolution of technology allows the development of computer algorithms that facilitate the diagnosis and evaluation of response after different oncological treatments and their non-invasive follow-up.

Brain metastases: Single-dose radiosurgery versus hypofractionated stereotactic radiotherapy: A retrospective study.

BACKGROUND: Radiosurgery is employed for the treatment of brain metastases. The aim of this study is to evaluate the efficacy and tolerability of single-dose radiosurgery (SRS) compared to hypofractionated stereotactic radiotherapy (hFSRT). MATERIALS AND METHODS: Between 2004 and 2018, we analyzed treatments of 97 patients with 135 brain metastases. Fifty-six patients were treated with SRS, and 41 patients were treated with hFSRT. Median dose was 16 Gy (12-20 Gy) for the SRS group and 30 Gy in 5-6 fractions for the hFSRT group. hFSRT was used for larger lesions and lesions located near critical structures. Kaplan-Meier curves were constructed for overall survival (OS) and local control (LC). RESULTS: Median age was 64 years (range, 32-89 years). Median survival was 10 months (1-68 months). With a median follow-up of 10 months, no significant differences in OS between groups were found (P=0.21). LC for all patients was 67%. Local progression-free survival (LPFS) at 6 months and 1 year was 71% and 60% for the SRS group, respectively, and 80% and 69% for the hFSRT group, respectively (P=0.93). Although hFSRT was used for larger lesions and lesions in adverse locations, LPFS was not inferior compared to lesions treated with SRS. We observed acute toxicity grade 1-2 in 25 patients (25.8%). Late complications were observed in 11 patients (11.3%). Acute and late toxicity was similar in the SRS- and hFSRT-treated patients (P=0.63 and P=0.11, respectively). Brain recurrence occurred in 37.5% and 14.6% in the hFSRT and SRS group, respectively (P=0.06). CONCLUSIONS: Since patients treated with hFSRT exhibited similar survival and LPFS rates without differences in toxicity compared to those treated with SRS, hFSRT can be beneficial, particularly for patients with brain metastases. RELEVANCE FOR PATIENTS: Hypofractionated schemes in stereotactic radiosurgery offers treatment alternatives to patients with large lesions or lesions near critical structures.