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Hepatocellular carcinoma (HCC) carries significant morbidity and mortality. Management of the HCC requires a multidisciplinary approach. Surgical resection and liver transplantation are the gold standard options for the appropriate settings. Stereotactic body radiation therapy (SBRT) has emerged as a promising treatment modality in managing HCC; its use is more studied and well-established in advanced HCC (aHCC). Current clinical guidelines universally endorse SBRT as a viable alternative to radiofrequency ablation (RFA), transarterial chemoembolisation (TACE), and transarterial radioembolisation (TARE), a recommendation substantiated by literature demonstrating comparable efficacy among these modalities. In early-stage HCC, SBRT primarily manages unresectable tumours unsuitable for ablative procedures such as microwave ablation and RFA. SBRT has been incorporated as a modality to downstage tumours or as a bridge to transplant. In the case of intermediate or advanced HCC, SBRT offers excellent results either as a single modality or adjunct to other locoregional modalities such as TACE/TARE. Recent data from late-stage HCC patients illustrate the effectiveness of SBRT in achieving local tumour control while minimising damage to surrounding healthy liver tissue. It has promising local control of approximately 80-90% in managing HCC. Additional prospective data comparing the efficacy of SBRT with the first-line recommended therapies such as RFA, TACE, and surgery are essential. The standard of care for patients with advanced/metastatic disease is systemic therapy (immunotherapy/tyrosine kinase inhibitors). SBRT, in combination with immune-checkpoint inhibitors, has an immune-modulatory effect that results in a synergistic effect. Recent findings indicate that the combination of immunotherapy and SBRT in HCC is well-tolerated and exhibits synergistic effects. Further exploration of diverse immunotherapy and radiotherapy strategies is essential to identify the appropriate time for combination treatments and to optimise dose and fraction regimens. Prospective, randomised studies are imperative to establish SBRT as the primary treatment for HCC.

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The management of colorectal cancer liver metastases requires a multidisciplinary approach, which may incorporate systemic therapy, surgery, or local ablative therapies. Stereotactic body radiation therapy (SBRT) is a non-invasive highly conformal radiation technique that enables the delivery of large doses of radiation in a few fractions to well-defined targets using image-guidance and motion management. For selected patients with colorectal cancer liver metastases, stereotactic body radiation therapy can be delivered safely, with excellent long-term local control and overall survival. The purpose of this clinical practice review is to review the background, indications, and treatment details of stereotactic body radiation therapy for the treatment of colorectal liver metastases. SBRT for colorectal cancer liver metastases may be considered for patients with oligometastatic colorectal cancer in combination with surgery or other locally ablative therapies; for patients who are not candidates for surgical resection; or after failure of resection or other ablative therapies. When planning SBRT both a computed tomography and magnetic resonance imaging simulation may be obtained, where feasible, for target delineation. One or 3 fraction SBRT can be considered for lesions away from the central liver and luminal organs at risk, whereas 5 fraction SBRT is preferred otherwise. Image-guidance and motion management strategies are essential components of liver SBRT and will guide the creation of relevant internal and planning target volume margins. For lesions in close proximity to or overlapping with organs-at-risk, the balance between adequate local control and potential for cure with potential acute and late toxicity must be carefully considered.

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Background: In oligometastatic colorectal cancer (CRC), stereotactic body radiation therapy (SBRT) represents a valid non-invasive local ablative treatment with high rates of local control (LC) and a low toxicity profile. This literature review was performed to evaluate the clinical benefit and toxicity of SBRT on non-liver metastases in CRC oligometastatic patients. Methods: After searching PubMed, Medscape and Embase databases, 18 retrospective studies focused on body oligometastases excluding bone metastases were included in the analysis. Results: A total of 1,450 patients with 3,227 lung metastases and 53 patients with 66 nodes lesions were analyzed. BED10 ranged from 76 to 180 Gy. In the lung group, the LC rate was 62-91%, 54-81% and 56-77% after 1, 3 and 5 years, respectively. In the nodes group, the 3-year LC rate was 65-75%. The 1-, 3- and 5-year OS rates were 73-100%, 51-64% and 34-43%, respectively for the lung group, and 63-81% at 3 years for the nodes group. Conclusions: In CRC patients with non-liver oligometastases, the use of SBRT is effective and safe reaching high LC and survival, with few severe side effects. However, prospective randomized studies are needed to validate the results. These studies will also be useful for identifying any predictive factors that allow us to select the subgroup of patients who benefit from SBRT.

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Background and Objective: Stereotactic body radiation therapy (SBRT) is a highly conformal technique of external beam radiotherapy precisely delivering high total (ablative) doses in a small number of fractions to clearly defined target volumes. Its development enabled efficient and safe radiation treatments in patients with localized hepatocellular cancer (HCC) unsuitable for other local treatment options. Moreover, it can be easily combined with several other therapy approaches. Thus, the aim of this narrative review is to outline the current role of SBRT in the multifocal treatment of HCC patients. Methods: We searched PubMed for articles dealing with SBRT alone, in combination with other local or systemic treatments or in comparison to other local treatments in patients with HCC. This included original articles, reviews and conceptional articles dealing with the technique of SBRT. All articles were analysed for suitability by two independent reviewers. Key Content and Findings: This review summarizes the currently available evidence for SBRT as a definitive treatment for HCC as well as its role within combination approaches including bridging to transplantation. SBRT is an effective and safe definitive treatment option in patients with localized HCC unsuitable for surgery and/or other local therapies based on retrospective and prospective series. Its combination with other local treatments yields superior results compared to single modality treatment based on non-randomized data. A growing number of prospective trials confirmed at least similar if not superior rates of local control with low toxicities compared to well established other local treatments even in non-selected patients. Conclusions: SBRT is a promising tool in the treatment of HCC. It can be used either as definitive treatment, within combination approaches or as a bridging tool. Several phase III trials comparing SBRT with other local options are ongoing, which will further clarify its encouraging role.

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PURPOSE: The aim of this study is to determine the effect of forcing and filling the electron density (ED) to 1.0 of the planning target volume (PTV) overdose distribution in lung SBRT treatment leading to shortening patient treatment time and increasing patient comfort by reducing MU/fraction due to ED manipulation effect. METHODS: In this study, 36 lung SBRT plans of 12 suitable patients who prescribed a total dose of 50 Gy in five fractions were generated with Monaco v.5.10 TPS using the Monte Carlo (MC) algorithm and volumetric modulated arc therapy (VMAT) technique by PTV ED values forcing as well as filling to 1.0 and comparatively assessed. The first group of plans was created by using the patient's original ED, second and third groups of plans were reoptimized by forcing and filling the ED of PTV to 1.0, respectively, therefore acquiring a new dose distribution which lead to comparatively assessment the effects of changes in ED on PTV and OAR doses. RESULTS: Assessment of treatment plans revealed that mean MU/fx numbers were decreased by 76% and 75.25% between Groups 1 and 2, Groups 1 and 3, respectively. The number of segments was also reduced in Group 1 by up to 15% compared with Groups 2 and 3. Maximum HI and CI differences for PTV between Groups 1 and 2 were less than 1% and Groups 1 and 3 were 1.5% which indicates all 3 group plans were comparable in terms of dose distribution within PTV. CONCLUSIONS: Forcing and filling the ED of PTV to 1.0 strategy has provided reduced a number of segments and MU/fx without a significant change in PTV mean and maximum doses, thereby decreasing treatment time and patient discomfort during treatment. This process should be considered in line of a potential number of patients as well as prescribed dose and MU/fx numbers.

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BACKGROUND: Surgery has been the standard procedure for resectable primary LC. Survival after stereotactic body radiation therapy, another treatment, is significantly biased due to preponderance of data from patients deemed unsuitable for surgery. We examined survival of patients refusing surgery in favor of radiation therapy. METHODS: We used the Surveillance, Epidemiology, and End Results database to identify patients with primary Stage I NSCLC diagnosed between 2007 and 2016. Patients were excluded if it was unknown if they were recommended for surgery or if surgery was contraindicated. Multiple predictors were assessed: radiation versus surgery, age at diagnosis, sex, race/ethnicity, health insurance status, marital status, tumor size, and histology. A multivariate analysis was performed to estimate hazard ratios and generate Kaplan-Meier survival curves. RESULTS: When adjusted for confounding variables, survival was greater for patients undergoing surgical resection than those refusing surgery in favor of radiation (HRadj 2.66; 95% CI: 2.27-3.11, p < 0.001) or for those receiving no standardized treatment (HRadj 4.43; 95% CI: 3.57-5.50, p < 0.001). CONCLUSIONS: SBRT is an effective treatment for inoperable early LC but there is limited data comparing outcomes against surgical resection. When eligible for both, patients refusing surgery and choosing radiation had worse survival when adjusting for variables including age, tumor size, and histology, and suggests that surgical resection is a superior treatment modality.

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Introduction: Androgen deprivation therapy has been shown to improve cancer control when combined with radiotherapy. Relugolix is an oral GnRH receptor antagonist that achieves rapid profound testosterone suppression, which may increase the perception and/or impact of fatigue. This study sought to evaluate neoadjuvant relugolix-induced fatigue in prostate cancer patients prior to the start of stereotactic body radiation therapy (SBRT). Methods: Relugolix was initiated at least two months before SBRT. The 13-item Functional Assessment of Chronic Illness Therapy-Fatigue (FACIT-F) questionnaire was collected at baseline and one hour prior to SBRT initiation. A five-point scale was used to score individual items. Overall scores range from 0-52 and individual item scores were converted to 0-100, with higher scores reflecting less fatigue. Five "experience" items explored self-perceptions of fatigue, and eight "impact" items sought to evaluate the effect of fatigue on daily activities. Items were evaluated for statistical significance (paired t-test, p < 0.05) and clinical significance (minimally important difference (MID); 0.5 standard deviation from baseline). Results: Between March 2021 to December 2023, 89 men were treated at Georgetown with neoadjuvant relugolix and SBRT. Mean age was 71 years (range: 49-87). Median initiation of relugolix was 4.5 months prior to SBRT (range: 2-14.2 months). 93% patients achieved castration (testosterone levels ≤ 50 ng/dL) and 85% patients achieved profound castration (testosterone levels ≤ 20 ng/dL). 87 patients completed the FACIT-F questionnaire, with an average overall score of 45.6 at baseline and 41.0 at SBRT initiation. This difference was statistically and clinically significant (p < 0.01, MID = 3.55). Patients experienced an increase in fatigue for 12 of 13 items, with statistically significant changes for 11 items. Three of five experience items showed a clinically significant increase in fatigue. Only two of eight impact items were clinically significant. Discussion: Our study shows that relugolix significantly increases fatigue, affecting multiple areas of life. While the fatigue does not appear to generally impact a patient's ability to carry out normal activities, patients demonstrate frustration with being too tired for these activities. It is essential for clinicians to counsel prostate cancer patients on the impact of neoadjuvant relugolix on quality-of-life issues like fatigue.

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This retrospective study was performed to evaluate plan quality and treatment delivery parameters of stereotactic body radiation therapy (SBRT) for prostate cancer. The study utilized different isocentric modulated techniques: intensity modulated radiotherapy (IMRT) and volumetric modulated arc therapy (VMAT) using 6 MV flattening filter (FF) and 10 MV flattening filter-free beams (FFF). Fifteen retrospective prostate cancer patients were selected for this study. Sixty plans were created with an SBRT-prescribed dose of 36.25 Gy delivered in five fractions. Planning target volume (PTV) coverage, plan quality indices, doses delivered to organs at risk (OARs), and treatment delivery parameters were compared for all plans. It turned out that VMAT plans, particularly those using the FFF beam, provided superior target conformality and a steeper dose gradient as compared to IMRT plans. Additionally, VMAT plans showed better OARs sparing compared to IMRT plans. However, IMRT plans delivered a lower maximum dose to the target than VMAT plans. Importantly, the VMAT plans resulted in reduced treatment delivery parameters, including beam on time (BOT), monitor unit (MU), and modulation factor (MF), compared to IMRT plans. Furthermore, a statistically significant difference was observed in BOT and mean body dose between FF and FFF beams, with FFF beams showing superior performance. Considering all results, VMAT using 10 MV (FFF) is suggested for treating prostate cancer patients with SBRT. This offers the fastest delivery in addition to maintaining the highest plan quality.

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To compare the dosimetric differences in volumetric modulated arc therapy (VMAT) and intensity modulated proton therapy (IMPT) in stereotactic body radiation therapy (SBRT) of multiple lung lesions and determine a normal tissue complication probability (NTCP) model-based decision strategy that determines which treatment modality the patient will use. A total of 41 patients were retrospectively selected for this study. The number of patients with 1-6 lesions was 5, 16, 7, 6, 3, and 4, respectively. A prescription dose of 70 GyRBE in 10 fractions was given to each lesion. SBRT plans were generated using VMAT and IMPT. All the IMPT plans used robustness optimization with ± 3.5% range uncertainties and 5 mm setup uncertainties. Dosimetric metrics and the predicted NTCP value of radiation pneumonitis (RP), esophagitis, and pericarditis were analyzed to evaluate the potential clinical benefits between different planning groups. In addition, a threshold for the ratio of PTV to lungs (%) to determine whether a patient would benefit highly from IMPT was determined using receiver operating characteristic curves. All plans reached target coverage (V70GyRBE ≥ 95%). Compared with VMAT, IMPT resulted in a significantly lower dose of most thoracic normal tissues. For the 1-2, 3-4 and 5-6 lesion groups, the lung V5 was 29.90 ± 9.44%, 58.33 ± 13.35%, and 81.02 ± 5.91% for VMAT and 11.34 ± 3.11% (p < 0.001), 21.45 ± 3.80% (p < 0.001), and 32.48 ± 4.90% (p < 0.001) for IMPT, respectively. The lung V20 was 12.07 ± 4.94%, 25.57 ± 6.54%, and 43.99 ± 11.83% for VMAT and 6.76 ± 1.80% (p < 0.001), 13.14 ± 2.27% (p < 0.01), and 19.62 ± 3.48% (p < 0.01) for IMPT. The Dmean of the total lung was 7.65 ± 2.47 GyRBE, 14.78 ± 2.75 GyRBE, and 21.64 ± 4.07 GyRBE for VMAT and 3.69 ± 1.04 GyRBE (p < 0.001), 7.13 ± 1.41 GyRBE (p < 0.001), and 10.69 ± 1.81 GyRBE (p < 0.001) for IMPT. Additionally, in the VMAT group, the maximum NTCP value of radiation pneumonitis was 73.91%, whereas it was significantly lower in the IMPT group at 10.73%. The accuracy of our NTCP model-based decision model, which combines the number of lesions and PTV/Lungs (%), was 97.6%. The study demonstrated that the IMPT SBRT for multiple lung lesions had satisfactory dosimetry results, even when the number of lesions reached 6. The NTCP model-based decision strategy presented in our study could serve as an effective tool in clinical practice, aiding in the selection of the optimal treatment modality between VMAT and IMPT.

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Background: Stereotactic body radiation therapy (SBRT) is often delivered in patients with oligometastatic disease (OMD). However, the specific subset of patients with polymetastatic non-small cell lung cancer (NSCLC) on novel systemic therapies who develop induced oligopersistant disease (OpersisD) or oligoprogressive disease (OprogD), as defined by the European Organisation for Research and Treatment of Cancer (EORTC) OMD classification, has not been well described. This study explores the outcomes of patients treated with this strategy. Methods: Patients with stage IV NSCLC being treated with osimertinib or immune checkpoint inhibitors (ICIs) who received extracranial SBRT for OpersisD or OprogD were identified in our retrospective analysis. Outcomes reported include progression-free survival (PFS), time to change of systemic treatment (TTCST), overall survival (OS), local control (LC) and treatment-related toxicity. Results: Forty-nine patients received SBRT for OpersisD (34.7%) or OprogD (65.3%) at a median of 5.8 and 15.3 months after start of systemic therapy, respectively. 55.1% received concurrent osimertinib and 44.9% received ICI. Seventy-seven extracranial lesions were treated with various fractionation schemas. At a median of 18.8 months follow-up from first SBRT, LC was achieved in 92.2% of total lesions treated (71). The 1-year OS was 91.7% for OpersisD and 83.3% for OprogD. OpersisD compared to OprogD had a longer median PFS (18.3 vs. 6.1 months) and longer median TTCST (23.6 vs. 13.5 months), median OS was not reached for either cohort. On multivariate analysis, patients treated with osimertinib had shorter PFS (HR: 2.20; 95% CI: 1.01-4.82; P=0.048) and shorter TTCST (HR: 2.83; 95% CI: 1.09-7.33; P=0.032). One patient (2%) experienced grade 3 pneumonitis after SBRT, and no grade 4-5 toxicities were reported with SBRT treatment. Conclusions: This study indicates that SBRT for OpersisD or OprogD in Stage IV NSCLC patients on osimertinib or ICIs is safe, very well tolerated, and may prolong the time before needing a shift in systemic therapy. Further prospective research is needed to validate and expand upon these findings.

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OPINION STATEMENT: The treatment of oligometastatic genitourinary cancers is a rapidly advancing field with ablative radiotherapy as one of the critical treatment components. The oligometastatic disease state, which can be defined as 1-5 metastatic sites with a controlled primary, represents a distinct clinical state where comprehensive ablative local therapies may provide improved outcomes. Enhanced imaging has increased the number of patients identified with oligometastatic disease. Evidence for improved outcomes with metastasis-directed therapy (MDT) in oligometastatic genitourinary cancers is increasing, and previously published outcome data continues to mature with an increasing body of prospective data to inform the role of MDT in histology-specific settings or in the context of systemic therapy. In select patients, MDT can offer benefits beyond improved local control and allow for time off of systemic therapy, prolonged time until next therapy, or even the hope of cure. However, treatment decisions for locally ablative therapy must be balanced with consideration towards safety. There are exciting advances in technologies to target and adapt treatment in real-time which have expanded options for safer delivery and dose escalation to metastatic targets near critical organs at risk. The role of systemic therapies in conjunction with MDT and incorporation of tumor genetic information to further refine prognostication and treatment decision-making in the oligometastatic setting is actively being investigated. These developments highlight the evolving field of treatment of oligometastatic disease. Future prospective studies combining MDT with enhanced imaging and integrating MDT with evolving systemic therapies will enable the optimal selection of patients most likely to benefit from this "all-or-none" approach and reveal settings in which a combination of therapies could result in synergistic outcomes.

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There is considerable interest in the potential of stereotactic body radiation therapy (SBRT) combined with systemic therapy such as tyrosine kinase inhibitors (TKIs) or immune checkpoint inhibitors (ICIs). However, its efficacy and safety remain unclear. The purpose of this study was to evaluate the efficacy and safety of conducting SBRT during ICI or TKI treatment in different disease settings for patients with metastatic renal cell carcinoma (mRCC). A total of 16 studies were ultimately included. Under the random effects model, the pooled 1-year local control rate (1-yr LCR) and objective response rate (ORR) were 90% (95% confidence interval [CI]: 80%-95%, I 2 = 67%) and 52% (95% CI: 37%-67%, I 2 = 90%), respectively. SBRT concomitant with different systemic therapy yield significant different 1-yr LCR (p < 0.01) and ORR (p = 0.02). Regarding survival benefits, the pooled 1-year progression-free survival (1-yr PFS) and 1-year overall survival (1-yr OS) rates were 45% (95% CI: 29%-62%, I 2 = 91%) and 85% (95% CI: 76%-91%, I 2 = 66%), respectively. 1-yr PFS and 1-yr OS in different disease settings demonstrated significant difference (p < 0.01). As for toxicity, the pooled incidence of grade 3-4 adverse events was 14% (95% CI: 5%-26%, I 2 = 90%). This study highlights the feasibility of utilizing these strategies in mRCC patients, especially those with a low metastatic tumor burden.

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Introduction: Sexual function following local treatment for prostate cancer is an important quality of life concern. Relugolix is a novel oral GnRH receptor antagonist used in combination with radiation therapy in the treatment of unfavorable prostate cancer. It has been shown to achieve rapid and profound testosterone suppression. As a result, these very low testosterone levels may impact both sexual functioning and perceptions. This prospective study sought to assess neoadjuvant relugolix-induced sexual dysfunction prior to stereotactic body radiation therapy (SBRT). Methods: Between March 2021 and September 2023, 87 patients with localized prostate cancer were treated with neoadjuvant relugolix followed by SBRT per an institutional protocol. Sexual function and bother were assessed via the sexual domain of the validated Expanded Prostate Index Composite (EPIC-26) survey. Responses were collected for each patient at pre-treatment baseline and after several months of relugolix. A Utilization of Sexual Medications/Devices questionnaire was administered at the same time points to assess erectile aid usage. Results: The median age was 72 years and 43% of patients were non-white. The median baseline Sexual Health Inventory for Men (SHIM) score was 13 and 41.7% of patients utilized sexual aids prior to relugolix. Patients initiated relugolix at a median of 4.5 months (2-14 months) prior to SBRT. 95% and 87% of patients achieved effective castration (≤ 50 ng/dL) and profound castration (< 20 ng/dl) at SBRT initiation, respectively. Ability to have an erection, ability to reach orgasm, quality of erections, frequency of erections, and overall sexual function significantly declined following relugolix. There was a non- significant increase in sexual bother. Discussion: In concordance with known side effects of androgen deprivation therapy (ADT), neoadjuvant relugolix was associated with a significant decline in self-reported sexual function. However, patients indicated only a minimal and non-significant increase in bother. Future investigations should compare outcomes while on relugolix directly to GnRH agonist-induced sexual dysfunction.

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It remains highly unclear and debatable whether combining radiotherapy (RT) and immune checkpoint blocker (ICB) therapy yields improved outcomes compared to either modality alone. Whereas some randomized data have shown improved outcomes, others have not. As a result of these conflicting data, it is essential to reconcile differences in the data and postulate reasons thereof. This work seeks to address these discrepancies, and uses the lessons learned from both positive and negative trials, including the most cutting-edge data available, in order to guide future clinical trial design and clarify the ideal/expected role of combinatorial therapy going forward. Because RT offers two distinct contributions (cytoreductive (local) effects & immune-stimulating (systemic) effects), RT should complement immunotherapy by addressing immunotherapy-resistant clones, and immunotherapy should complement RT by addressing RT-resistant or out-of-field clones. RT is not merely a single "drug", but rather a constellation of diverse "drugs" that can be varied based on dose regimens, previous systemic therapy regimens, number of irradiated sites, treatment intent/location/timing, tumor biology, and individual patient immunological circumstances. These factors are discussed as an important explanation for the discrepancies in results of various randomized trials in heterogeneous populations and clinical settings, and these discrepancies may continue until trials of more uniform circumstances are designed to use particular RT paradigms that meaningfully add value to systemic therapy.

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Purpose: MR-guided radiotherapy (MRgRT) has the advantage of utilizing high soft tissue contrast imaging to track daily changes in target and critical organs throughout the entire radiation treatment course. Head and neck (HN) stereotactic body radiation therapy (SBRT) has been increasingly used to treat localized lesions within a shorter timeframe. The purpose of this study is to examine the dosimetric difference between the step-and-shot intensity modulated radiation therapy (IMRT) plans on Elekta Unity and our clinical volumetric modulated arc therapy (VMAT) plans on Varian TrueBeam for HN SBRT. Method: Fourteen patients treated on TrueBeam sTx with VMAT treatment plans were re-planned in the Monaco treatment planning system for Elekta Unity MR-Linac (MRL). The plan qualities, including target coverage, conformity, homogeneity, nearby critical organ doses, gradient index and low dose bath volume, were compared between VMAT and Monaco IMRT plans. Additionally, we evaluated the Unity adaptive plans of adapt-to-position (ATP) and adapt-to-shape (ATS) workflows using simulated setup errors for five patients and assessed the outcomes of our treated patients. Results: Monaco IMRT plans achieved comparable results to VMAT plans in terms of target coverage, uniformity and homogeneity, with slightly higher target maximum and mean doses. The critical organ doses in Monaco IMRT plans all met clinical goals; however, the mean doses and low dose bath volumes were higher than in VMAT plans. The adaptive plans demonstrated that the ATP workflow may result in degraded target coverage and OAR doses for HN SBRT, while the ATS workflow can maintain the plan quality. Conclusion: The use of Monaco treatment planning and online adaptation can achieve dosimetric results comparable to VMAT plans, with the additional benefits of real-time tracking of target volume and nearby critical structures. This offers the potential to treat aggressive and variable tumors in HN SBRT and improve local control and treatment toxicity.

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BACKGROUND: Stereotactic Body Radiotherapy (SBRT) is as a standard treatment for prostate cancer (PCa). Tight margins and high dose gradients are needed, and the precise localization of the target is mandatory. Our retrospective study reports our experience regarding the evaluation of intrafraction prostate motion during LINAC-based SBRT evaluated with a novel electromagnetic (EM) tracking device. This device consists of an integrated Foley catheter with a transmitter connected to a receiver placed on the treatment table. METHODS: We analyzed 31 patients who received LINAC-based SBRT using flattening filter-free (FFF) volumetric modulated arc therapy (VMAT). The patients were scheduled to be treated for primary (n = 27) or an intraprostatic recurrent PCa (n = 4). A simulation CT scan was conducted while the patients had a filled bladder (100-150 cc) and an empty rectum, and an EM tracking device was used. The same rectal and bladder conditions were employed during the treatment. The patients received 36.25 Gy delivered over five consecutive fractions on the whole prostate and 40 Gy on the nodule(s) visible via MRI, both delivered with a Simultaneous Integrated Boost approach. The CTV-to-PTV margin was 2 mm for both the identified treatment volumes. Patient positioning was verified with XVI ConeBeam-CT (CBCT) matching before each fraction. When the signals exceeded a 2 mm threshold in any of the three spatial directions, the treatment was manually interrupted. A new XVI CBCT was performed if this offset lasted >20 s. RESULTS: We analyzed data about 155 fractions. The median and mean treatment times, calculated per fraction, were 10 m31 s and 12 m44 s (range: 6 m36 s-65 m28 s), and 95% of the fractions were delivered with a maximum time of 27 m48 s. During treatment delivery, the mean and median number of XVI CBCT operations realized during the treatment were 2 and 1 (range: 0-11). During the treatment, the prostate was outside the CTV-to-PTV margin (2 mm), thus necessitating the stoppage of the delivery +/- a reacquisition of the XVI CBCT for 11.2%, 8.9%, and 3.9% of the delivery time in the vertical, longitudinal, and lateral direction, respectively. CONCLUSIONS: We easily integrated an EM-transmitter-based gating for prostate LINAC-based SBRT into our normal daily workflow. Using this system, a 2 mm CTV-to-PTV margin could be safely applied. A small number of fractions showed a motion exceeding the predefined 2 mm threshold, which would have otherwise gone undetected without intrafraction motion management.

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BACKGROUND: Tumor necrosis factor (TNF) is a multipotent cytokine involved in inflammation and anti-tumor activity. TNF-α exerts its function upon binding to TNF-receptor 1 (TNF-R1) and TNF-receptor 2 (TNF-R2). This study investigates the relationship of soluble (s) TNF-R1 levels in non-small-cell lung cancer (NSCLC) patients with treatment and overall survival. METHODS: In total, 134 NSCLC patients treated at the Medical Faculty of Martin Luther University Halle-Wittenberg between 2017 and 2019 were included in this study. Serum levels of sTNF-R1 were measured via ELISA at baseline and during and after treatment. A linear mixed-effects model was used to assess sTNF-R1 changes over time. Linear regression was applied to investigate the association between clinical characteristics and changes in sTNF-R1. Cox regression models were used to estimate associations with overall mortality. RESULTS: The estimated average sTNFR-1 at baseline was 2091.71 pg/mL, with a change of 6.19 pg/mL per day. Cox models revealed that the individual change in sTNF-R1 was more strongly associated with mortality than its baseline value, especially after adjusting for covariates. CONCLUSIONS: This study provides evidence that the individual change in sTNF-R1 levels during and after treatment were associated with the risk of mortality, suggesting the use of the sTNF-R1 trajectory as a prognostic marker.

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Hepatocellular carcinoma (HCC)is a common type of liver cancer with a poor prognosis, especially in patients with advanced stages or underlying liver disease. While surgical resection, liver transplantation, and ablation therapies have traditionally been the mainstay of treatment for HCC, radiation therapy has become increasingly recognized as an effective alternative, particularly for those who are not surgical candidates. Stereotactic Body Radiation Therapy (SBRT) is a highly precise form of radiation therapy that delivers very high doses of radiation to the tumor while sparing surrounding healthy tissue. Several studies have reported favorable outcomes with SBRT in HCC treatment. Moreover, SBRT can be used to treat recurrent HCC after prior treatment, offering a potentially curative approach in select cases. While SBRT has demonstrated its efficacy and safety in treating HCC, future studies are needed to further investigate the potential role of SBRT in combination with other treatments for HCC.

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Introduction: Injectable GnRH receptor agonists have been shown to improve cancer control when combined with radiotherapy. Prostate SBRT offers an abbreviated treatment course with comparable efficacy to conventionally fractionated radiotherapy. Relugolix is a new oral GnRH receptor antagonist which achieves rapid, sustained testosterone suppression. This prospective study sought to evaluate early testosterone suppression and PSA response following relugolix and SBRT for intermediate to high prostate cancer. Methods: Relugolix was initiated at least 2 months prior to SBRT. Interventions to improve adherence were not utilized. PSA and total testosterone levels were obtained prior to and 1-4 months post SBRT. Profound castration was defined as serum testosterone ≤ 20 ng/dL. Early PSA nadir was defined as the lowest PSA value within 4 months of completion of SBRT. Per prior trials, we examined the percentage of patients who achieved PSA level of ≤ 0.5 ng/mL and ≤ 0.2 ng/mL during the first 4 months post SBRT. Results: Between July 2021 and January 2023, 52 men were treated at Georgetown with relugolix (4-6 months) and SBRT (36.25-40 Gy in 5 fractions) per an institutional protocol (IRB 12-1775). Median age was 71 years. 26.9% of patients were African American and 28.8% were obese (BMI ≥30 kg/m2). The median pretreatment PSA was 9.1 ng/ml. 67% of patients were ≥ Grade Group 3. 44 patients were intermediate- and 8 were high-risk. Patients initiated relugolix at a median of 3.6 months prior to SBRT with a median duration of 6.2 total months. 92.3% of patients achieved profound castration during relugolix treatment. Poor drug adherence was observed in 2 patients. A third patient chose to discontinue relugolix due to side effects. By post-SBRT month 4, 87.2% and 74.4% of patients achieved PSA levels ≤ 0.5 ng/ml and ≤ 0.2 ng/ml, respectively. Discussion: Relugolix combined with SBRT allows for high rates of profound castration with low early PSA nadirs. We observed a 96% testosterone suppresion rate without the utilization of scheduled cues/reminders. This finding supports the notion that patients with localized prostate cancer can consistently and successfully follow an oral ADT protocol without daily reminders. Given relugolix's potential benefits over injectable GnRH receptor agonists, its usage may be preferred in specific patient populations (fear of needles, prior cardiovascular events). Future studies should focus on boundaries to adherence in specific underserved populations.