Search Results (169)

Pancreatic ductal adenocarcinoma (PDAC) remains one of the most lethal malignancies, with limited treatment options for patients with locally advanced or metastatic disease. Endoscopic ultrasound (EUS)-guided intra-tumoral radioactive implantation has emerged as a minimally invasive approach to enhance local tumor control while minimizing systemic toxicity. Among the available isotopes, phosphorus-32 (³²P) microparticle brachytherapy has demonstrated promising outcomes, including significant tumor regression, reductions in CA 19-9, and higher rates of tumor downstaging and surgical conversion when combined with systemic chemotherapy. Compared with stereotactic body radiotherapy (SBRT), ³²P delivers higher intratumoral radiation doses, spares adjacent healthy tissues, and can be administered during ongoing chemotherapy without treatment interruption. Additionally, preliminary evidence suggests that ³²P may modulate the tumor microenvironment, improving vascularity and enhancing chemotherapy efficacy. The procedure shows high technical success and a favorable safety profile, with minimal serious adverse events. Future directions include prospective randomized trials to validate its impact on survival, optimize dosing, and establish treatment protocols. EUS-guided intra-tumoral ³²P brachytherapy holds potential as a key component of multimodal therapy, bridging local tumor control and systemic disease management in PDAC. Full article

Background/Objectives: Stereotactic body radiation therapy (SBRT) is widely used for small lung tumors, but the physics of electron transport in low-density lungs remains incompletely understood. This study quantifies the effect of lung density on dosimetry for small lesions. Methods: To study the dosimetric parameters a pseudo patient option was chosen. A lung SBRT patient with a central lesion was modeled in the Eclipse treatment planning system using the AAA algorithm. Three target sizes (1.0, 1.5, and 2.0 cm) were planned with lung densities overridden from 0.1 to 1.0 g/cm³. Standard SBRT constraints were applied, and dosimetry indices (CI, HI, GI), maximum dose, and MU/Gy were recorded to see the pattern. Results: Dose–volume histograms (DVHs) showed marked dependence on both lesion size and lung density. Lower densities produced higher maximum doses (up to 135% at 0.1 g/cm³), steeper DVH tails, and significantly increased MU/Gy. Conformity was achievable in all cases, but at the cost of degraded homogeneity and gradient indices. At higher density (1.0 g/cm³), maximum dose values fell to 108–110% which is typical in non-lung cases. Conclusions: SBRT planning in low-density lungs requires substantially higher MU and results in greater dose spillage despite acceptable conformity. These findings highlight the importance of considering density effects when comparing clinical outcomes across institutions and selecting optimal plans, where minimizing MU/Gy may reduce unnecessary dose burden. Full article

Introduction: Metabolomics-based phylogenetic profiling of prostate cancer (PCa) patients before and after stereotactic body radiation therapy (SBRT) can provide insight into the way in which treatment outcomes relate to the underlying physiology and physiological responses of individual patients. It also offers the potential for helping identify precision biomarkers. Methods: In this study, we used integrated mass spectrometry to obtain untargeted serum metabolomics data from PCa patients (n = 55), which we then analyzed using a parsimony phylogenetic systems biology approach before correlating the results with the patients’ clinical parameters before and after treatment. Results: Radiotherapy (RT) generated five phylogenetic subgroups with distinct metabolomic profiles that did not correspond to hormonal treatment, risk assessment, metastasis, or PSA levels. PSA was neither a factor influencing clade membership nor an indicator of risk assessment or metastasis. Moreover, the hormone-treated patients did not form their own clade but were rather spread among the five clades. The same absence of correlation applied to risk assessment and metastasis. The 88 significantly altered pre-RT and 29 post-RT features showed aberrations in the metabolic pathways of purines, porphyrin, glycerophospholipids, and 2-methylglutaric acid, among others. Discussion: Significantly altered metabolites in a majority of patients who developed metastasis included D-tryptophan, carbamate, 5′-Benzoylphosphoadenosine, Phosphatidylcholine (PC), bilirubin, and hypoxanthine. In general, the cladogram offers a new perspective on evaluating the clinical variables that represent significant indicators of PCa progression, metastasis, and treatment response in individuals. Conclusions: Metabolic profiles and associated clinical phenotypes provided by this precision phylometabolomics approach may offer a deeper understanding of the metabolic factors and pathways implicated in cancer progression and metastasis and should contribute to the development of targeted treatments and more precise monitoring of cancer and cancer therapies. Full article

Background: This study aimed to analyse treatment outcomes, determine prognostic factors and assess the toxicity of reirradiation using high-dose-rate (HDR) brachytherapy for liver metastases in the oligometastatic stage of disease. Materials and Methods: The study included 59 patients who had previously undergone SBRT (stereotactic body radiation therapy) or HDR brachytherapy and experienced progression within (type 1) or outside (type 2) the irradiated area, but in a different location within the liver. Patients were divided according to the type of reirradiation and the reason for treatment. Local control (LC), progression-free survival (PFS) and overall survival (OS) were analysed in relation to the following factors: age; gender; performance status; tumour type; line of systemic treatment; location of extrahepatic metastases; type of reirradiation; time since previous irradiation; indication for treatment; size and number of metastases; dose; and degree of response to treatment. Treatment toxicity and the influence of dose, irradiation volume, number of metastases, time since previous radiotherapy and dose to the non-irradiated part of the liver on hepatic toxicity were also assessed. Results: With a median follow-up period of 13 months, the median LC, PFS and OS were 9, 8 and 13 months, respectively. The respective rates of partial regression (PR), stable disease (SD) and progressive disease (PD) were 32%, 44% and 12%. The most significant factors influencing LC were the degree of tumour shrinkage, with PFS influenced by the degree of tumour shrinkage and a low number of metastases, and OS influenced by the degree of tumour shrinkage, a low number of metastases and one to two lines of systemic therapy. Treatment toxicity was low, and there was no strong correlation between the dosimetric parameters of the treatment plan and the biochemical parameters of liver function. Conclusions: Brachytherapy is a safe and effective method of re-irradiating liver metastases. However, due to the limitations of the study, further investigation is required. Full article

Background/Objectives: Stereotactic body radiation therapy (SBRT) is a therapeutic option for hepatocellular carcinoma (HCC). This study reviewed outcomes and toxicities of SBRT for HCC using a gimbal-mounted linear accelerator and real-time monitoring system. Methods: A single-institution, retrospective review of SBRT for HCC using DTT between January 2018 and December 2020 was undertaken. Endpoints included local control (LC) and overall survival (OS). Results: A total of 74 patients with 82 tumors treated were identified. Median follow-up was 40.8 months. LC at 1, 3, and 5 years was 89.6%, 71.0%, and 59.9%, respectively. Median time to local failure was not reached. Median OS was 41.3 months (95% CI 30.7–51.8 months). OS at 1, 3, and 5 years was 89.2%, 60.6%, and 33.9%, respectively. On UVA, GTV ≥ 30 cm³ (p = 0.038), and PTV ≥ 150 cm³ (p = 0.010) were associated with an absolute drop in platelet count by ≥50,000/mm³ within six weeks of SBRT, while prior focal liver treatment (p = 0.097) showed a trend toward significance. Underlying viral cirrhosis (p = 0.033), A6 or higher pre-SBRT Child–Pugh score (p = 0.010), and pre-SBRT platelet count <100,000/mm³ (p = 0.017) were significant for a rise in Child–Pugh score of 2 points or more, and the volume of liver-GTV <1000 cm³ (p = 0.093) approached significance. Conclusions: SBRT using DTT is an effective therapeutic option for selected patients with HCC, providing acceptable local control and toxicity. Full article

Hepatocellular carcinoma (HCC) is the most common primary liver cancer. At the time of diagnosis, many HCC patients are not candidates for surgical resection and are considered for other locoregional therapies, including transarterial radioembolization (TARE) and stereotactic body radiation therapy (SBRT). To date only a few studies have explored the safety and efficacy of combining TARE and SBRT. Therefore, we aimed to evaluate it. Patients who received both SBRT and TARE from 2016 to 2024 were retrospectively evaluated for treatment-related toxicity based on criteria for adverse events (CTCAE v4.0). Treatment response was evaluated by modified response evaluation criteria for solid tumors (m-RECIST). We identified 12 patients with median age of 66.5 (range: 40, 87) and median follow up of 12 months. The median time between TARE and SBRT was 6.5 months (range: 1.5 to 24). Following the second treatment, ALBI grade remined the same among all patients at 3-month post treatment compared to baseline. Baseline CP was A among all patients and remained unchanged during follow-up and no higher than grade 3 clinical or biochemical toxicity was seen. The objective response rate (ORR) among patients receiving treatment to the same lesion was 100%. The combination treatment was consistent with prior studies in which the combination of TARE and SBRT has been shown to have good local control with few cases of grade 3 toxicity. Our study demonstrates that treatment with TARE and SBRT was safe and effective among our small sample of patients. Full article

Background: Liver resection remains the gold standard treatment for colorectal cancer (CRC) liver metastases, while stereotactic body radiotherapy (SBRT) offers an alternative for patients with unresectable metastases. However, the precise indications for SBRT, optimal radiation doses, and treatment regimens have yet to be definitively established. Methods: A total of 91 patients with 152 lesions underwent SBRT, receiving a total dose ranging from 40 to 60 Gy delivered in 4–5 fractions per lesion, with a median dose of 50 Gy. Results: The three-year local control (LC) and overall survival (OS) rates were 62.6% and 45.1%, respectively. No cases of Grade ≥ 3 toxicity were observed. Factors negatively affecting LC included metastasis diameter ≥ 2.7 cm and number of metastases ≥ 3, with hazard ratios (HR) of 2.73 and 2.24, respectively. A biologically effective dose (BED) of ≥137.7 Gy was associated with a significant improvement in local control (LC) (HR 0.25), a finding that was also confirmed by the inverse probability of treatment weighting (IPTW) analysis. Significant predictors for poorer OS included RAS gene mutations, metastasis diameter ≥ 2.6 cm, and synchronous metastases, with HRs of 2.27, 2.03, and 2.11, respectively. Landmark analysis demonstrated that local recurrence within 12 months after SBRT significantly reduced OS (HR 2.68). Conclusions: SBRT is a safe and effective method for achieving local control of CRC liver oligometastases. Further research is warranted to optimize treatment protocols and refine patient selection criteria. Full article

Background: To compare the costs of open retropubic radical prostatectomy (RRP), robotic-assisted radical prostatectomy (RALP), intensity-modulated radiation therapy (IMRT), low-dose brachytherapy (LDBT), stereotactic body radiotherapy (SBRT), cryotherapy (Cryo), and high-intensity focused ultrasound (HIFU) for low/intermediate-risk prostate cancer (PCa), from the healthcare system perspective. Methods: This retrospective, IRB-approved study compared the costs and charges of primary treatment options for localized PCa at Duke University Hospital between January 2018 and December 2019. We identified cases by querying the relevant disease, procedural, and charge codes from Duke Finance. Consecutive cases with NCCN high-risk disease, prior treatment, or missing institutional financial information were excluded. Costs were calculated from the point at which the treatment option was selected until the last treatment session (SBRT and IMRT) or hospital discharge (other modalities). All modalities except RRP were considered technology-intensive. Results: A total of 552 patients with a mean age of 65.0 years met the inclusion criteria. NCCN risk categories included 85 (13%) low, 218 (41%) favorable-intermediate, and 249 (46%) unfavorable-intermediate risk cases. RALP, RRP, Cryo, and HIFU were single-session treatments, whereas IMRT, SBRT, and LDBT were delivered over multiple sessions. IMRT and SBRT were the most expensive modalities, followed by RALP, HIFU, LDBT, Cryo, and RRP. The number of sessions (ρ = 0.55, p < 0.001) and being technology-intensive (ρ = 0.58, p < 0.001) were significantly correlated with treatment costs. Conclusions: In this cohort of PCa patients, treatment costs were highest for IMRT and SBRT, followed by RALP, HIFU, LDBT, Cryo, and RRP. The number of treatment sessions was a significant predictor of higher costs. Full article

Stereotactic body radiation therapy (SBRT) for lung tumors near the chest wall often causes significant chest wall pain (CWP), negatively impacting patients’ quality of life. The mechanisms behind SBRT-induced CWP remain unclear and may involve multiple factors. We investigated crosstalk between radiation-activated osteoclasts and sensory neurons, focusing on osteoclast-derived factors in CWP. Using murine pre-osteoclast cell line Raw264.7, we induced differentiation with Receptor Activator of Nuclear Factor kappa-beta Ligand (RANKL), followed by 10 Gy gamma-irradiation. Conditioned media (C.M) from irradiated osteoclasts was used to treat sensory neuronal cultures from mouse dorsal root ganglia. Neuronal cultures were also exposed to 10 Gy radiation, with and without osteoclast co-culture. Osteoclast markers and pain-associated neuropeptides were analyzed using RT-qPCR and histochemical staining. Osteoclasts differentiation and activity were inhibited using osteoprotegerin (OPG) and risedronate. High-dose radiation significantly increased the size of tartrate-resistant-acid-phosphatase (TRAP)-positive osteoclasts (1.36-fold) and activity biomarkers (Ctsk, 1.35-fold, Mmp9, 1.76-fold). Neurons treated with C.M from irradiated osteoclasts showed ~1.5-fold increase in Calca (calcitonin gene-related peptide) and Tac1 (substance P) expression, which was mitigated by osteoclast inhibitors. These findings suggest that radiation enhances osteoclast activity and promotes pain signaling. Osteoclast inhibitors may represent a therapeutic strategy to reduce CWP and improve quality of life. Full article

Background/Objectives: Patients with non-small cell lung cancer (NSCLC) being evaluated for stereotactic body radiation therapy (SBRT) are frequently staged non-invasively with positron emission tomography/computed tomography (PET/CT). Performing endobronchial ultrasound-guided transbronchial needle aspiration (EBUS-TBNA) in addition to PET/CT scanning may increase clinical certainty in lymph node staging, but the magnitude of added benefit of EBUS-TBNA over non-invasive staging methods is unclear. Methods: A single-center prospective cohort study involving patients with suspected or confirmed Stage I or IIa NSCLC referred for EBUS-TBNA prior to SBRT was performed. The primary outcome was concordance between PET/CT and EBUS-TBNA for nodal metastases. Secondary endpoints included sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) of PET/CT, and clinical outcomes based on staging results. Results: Among 115 patients, the concordance between PET/CT and EBUS-TBNA was 84.3% (95% CI: 0.76 0.90). EBUS-TBNA led to a stage shift in 15.7% of cases: 4 of 98 PET/CT N0 patients (4.1%) had nodal metastases, while 14 of 17 PET/CT N1 patients (82.4%) were downstaged to N0. PET/CT sensitivity was 42.9% (95% CI: 0.09–0.81), specificity 87% (95% CI: 0.79–0.93), PPV 17.6% (95% CI: 0.04–0.43), and NPV 95.9% (95% CI: 0.90–0.99). PET/CT-positive, EBUS-TBNA-negative patients had worse survival (HR 4.25, 95% CI: 1.24–14.53, p = 0.021) compared with double-negative patients. Conclusions: EBUS-TBNA improves staging accuracy over PET/CT in early-stage NSCLC, impacting SBRT candidacy. However, PET/CT-positive, EBUS-TBNA-negative patients had worse outcomes in comparison to double-negative patients, suggesting a need for additional therapy or surveillance in that population. Full article

Background: Stereotactic body radiation therapy (SBRT) has proven effective in controlling spinal lesions with minimal toxicity, primarily due to its ability to limit spinal cord dose. Recent advances in MR-linac (MRL) technology offer superior spinal cord visualization and real-time gating, which can facilitate dose escalation in spinal tumor treatment while maintaining safety. Purpose: This study aimed to optimize motion management for spine SBRT on an MRL by analyzing patient-specific motion dynamics and evaluating the most effective registration structures. We hypothesized that baseline shifts (BLS) would improve delivery efficiency while maintaining spinal cord dose constraints. The goal was to establish displacement thresholds and assess the role of baseline shift correction adaptative planning in improving treatment delivery efficiency. Methods: Twelve patients underwent two MRI sessions on the MRL. The optimal registration structure was identified, and intrafraction motion was assessed to calculate delivery efficiency. Baseline shift (BLS) simulations were applied for five cases that showed significant motion and suboptimal delivery efficiency, and the dosimetric impact of the BLS was evaluated. The simulated BLS-based plan adaptation was implemented via a segment aperture morphing adapt-to-position workflow. Results: The most stable registration structure was the spinal canal plus three adjacent vertebrae. Cine imaging revealed average intrafraction motion (95th to 5th percentiles) of 0.8 ± 0.5 mm in the right-left (RL) direction, 0.9 ± 0.6 mm in the anterior–posterior (AP) direction, and 0.7 ± 0.5 mm in the SI direction. Simulated BLS improved delivery efficiency to >80% in all but one case, with a ±1 mm displacement threshold tolerance. While target coverage remained consistent after BLS simulation, the spinal cord dose increased by 7–60%, exceeding the 14 Gy constraint in three of the five simulated cases. Conclusions: Cine imaging and BLS can enhance delivery efficiency in spine SBRT but may increase spinal cord dose. These findings underscore the need for careful patient selection, advanced motion management, and patient-specific BLS protocols. Full article

Objectives: We investigated the performance of a slow computed tomography (CT) protocol to reduce alignment errors arising from motion when using CT-on-rail (CTOR) for image guidance for patients receiving thoracic stereotactic body radiation therapy (SBRT). Methods: A Quasar lung phantom with a moving tumor was programmed with three breathing rates and three motion amplitudes. MIP and average 4DCT images were used for contouring and alignment, respectively. Ten CTOR images were obtained for each of the breathing rates and amplitudes, under both CT protocols. We used in-house CAT software for image guidance, centering the tumor in the lung window within the gross tumor volume contour. Longitudinal coordinate reproducibility was compared between the two protocols. We also retrospectively analyzed CBCT SBRT image guidance alignment data from 31 patients to evaluate the systematic error in the longitudinal direction between simulation and daily treatments. Results: The mean (standard deviation) alignments (mm) for the standard and slow CT protocol ranged from 0.7 (0.68) and 1.0 (0.0), respectively, for the 28 BPM breathing rate and 5 mm amplitude combination to 5.2 (2.0) and 1.6 (0.52) for the 8 BPM breathing rate and 15 mm amplitude combination. Our retrospective analysis of patient alignment data showed a notable systematic difference in the relative bone and gross tumor volume alignment between the simulation and daily cone beam CT datasets. The mean longitudinal difference was −0.19 cm (standard deviation, 0.17 cm; range, 0.28 cm to −1.14 cm). Therefore, the position of the vertebral body cannot be used as a surrogate for mean tumor position in the longitudinal direction. Longitudinal position must be accurately determined for each patient using multiple CT images. Conclusions: A slow CT protocol improved the alignment with slower breathing rates being more challenging. A 5 mm PTV is not sufficient for tumor motion greater than 9 mm. Averaging the coordinates from multiple CTOR images is recommended. Full article

Despite advances in surgery, chemotherapy, and radiation treatments for pancreatic ductal adenocarcinoma (PDAC), 5-year survival rates remain at nearly 11%. Cholangiocarcinoma, while not as severe, also possesses similar survival rates. Fewer than 20% of patients are surgical candidates at time of diagnosis; therefore, it is imperative that alternative therapies are effective for non-surgical patients. There are several thermal ablative techniques, including radiofrequency ablation (RFA), high-intensity focused ultrasound (HIFU), microwave ablation (MWA), alcohol ablation, stereotactic body radiotherapy (SBRT), cryoablation, irreversible electroporation (IRE), biliary intraluminal brachytherapy, and biliary photodynamic therapy (PDT). Emerging literature in animal models and human patients has demonstrated that endoscopic ultrasound (EUS)-guided RFA (EUS-RFA) prevents tumor progression through coagulative necrosis, protein denaturation, and activation of anticancer immunity in local and distant tumor tissue (abscopal effect). RFA treatment has been shown to not only reduce tumor-associated immunosuppressive cells but also increase functional T cells in distant tumor cells not treated with RFA. The remarkable ability to reduce tumor progression and promote tumor microenvironment (TME) remodeling makes RFA a very promising non-surgical therapy technique that has the potential to reduce mortality in this patient population. EUS-RFA offers superior precision and safety compared to other ablation techniques for pancreatic and biliary cancers, due to real-time imaging capabilities and minimally invasive nature. Future research should focus on optimizing RFA protocols, exploring combination therapies with chemotherapy or immunotherapy, and expanding its use in patients with metastatic disease. This review article will explore the current data and underlying pathophysiology of EUS-RFA while also highlighting the role of ablative therapies as a whole in immune activation response. Full article

Introduction: Radiomics is the extraction of non-invasive and reproducible quantitative imaging features, which may yield mineable information for clinical practice implementation. Quantification of lung function through radiomics could play a role in the management of patients with pulmonary lesions. The aim of this study is to test the capability of radiomic features to predict pulmonary function parameters, focusing on the diffusing capacity of lungs to carbon monoxide (DL_CO). Methods: Retrospective data were retrieved from electronical medical records of patients treated with Stereotactic Body Radiation Therapy (SBRT) at a single institution. Inclusion criteria were as follows: (1) SBRT treatment performed for primary early-stage non-small cell lung cancer (ES-NSCLC) or oligometastatic lung nodules, (2) availability of simulation four-dimensional computed tomography (4DCT) scan, (3) baseline spirometry data availability, (4) availability of baseline clinical data, and (5) written informed consent for the anonymized use of data. The gross tumor volume (GTV) was segmented on 4DCT reconstructed phases representing the moment of maximum inhalation and maximum exhalation (Phase 0 and Phase 50, respectively), and radiomic features were extracted from the lung parenchyma subtracting the lesion/s. An iterative algorithm was clustered based on correlation, while keeping only those most associated with baseline and post-treatment DL_CO. Three models were built to predict DL_CO abnormality: the clinical model—containing clinical information; the radiomic model—containing the radiomic score; the clinical-radiomic model—containing clinical information and the radiomic score. For the models just described, the following were constructed: Model 1 based on the features in Phase 0; Model 2 based on the features in Phase 50; Model 3 based on the difference between the two phases. The AUC was used to compare their performances. Results: A total of 98 patients met the inclusion criteria. The Charlson Comorbidity Index (CCI) scored as the clinical variable most associated with baseline DL_CO (p = 0.014), while the most associated features were mainly texture features and similar among the two phases. Clinical-radiomic models were the best at predicting both baseline and post-treatment abnormal DL_CO. In particular, the performances for the three clinical-radiomic models at predicting baseline abnormal DL_CO were AUC₁ = 0.72, AUC₂ = 0.72, and AUC₃ = 0.75, for Model 1, Model 2, and Model 3, respectively. Regarding the prediction of post-treatment abnormal DL_CO, the performances of the three clinical-radiomic models were AUC₁ = 0.91, AUC₂ = 0.91, and AUC₃ = 0.95, for Model 1, Model 2, and Model 3, respectively. Conclusions: This study demonstrates that radiomic features extracted from healthy lung parenchyma on a 4DCT scan are associated with baseline pulmonary function parameters, showing that radiomics can add a layer of information in surrogate models for lung function assessment. Preliminary results suggest the potential applicability of these models for predicting post-SBRT lung function, warranting validation in larger, prospective cohorts. Full article

Background/Objectives: Proton therapy delivers highly conformal doses to the target area without producing an exit dose, minimizing cumulative doses to healthy liver tissue. This study aims to evaluate current practices, challenges, and variations in the implementation of proton stereotactic body radiation therapy (SBRT) and hypofractionated therapy for liver malignancies, with the goal of providing a technical assessment to promote broader adoption and support future clinical trials. Methods and Materials: An extensive survey was conducted by NRG Oncology across North American proton treatment centers to assess the current practices of proton liver SBRT and hypofractionated therapy. The survey focused on key aspects, including patient selection, prescription and normal tissue constraints, simulation and motion management, treatment planning, quality assurance (QA), treatment delivery, and the use of image-guided radiation therapy (IGRT). Results: This survey captures the current practice patterns and status of proton SBRT and hypofractionated therapy in liver cancer treatment.  Proton therapy is increasingly preferred for treating inoperable liver malignancies due to its ability to minimize healthy tissue exposure. However, the precision required for proton therapy presents challenges, particularly in managing uncertainties and target motion during high-dose fractions and short treatment courses. Survey findings revealed significant variability in clinical practices across centers, highlighting differences in motion management, dose fractionation schedules, and QA protocols. Conclusion: Proton SBRT and hypofractionated therapy offer significant potential for treating liver malignancies. A comprehensive approach involving precise patient selection, treatment planning, and QA is essential for ensuring safety and effectiveness. This survey provides valuable insights into current practices and challenges, offering a foundation for technical recommendations to optimize the use of proton therapy and guide future clinical trials. Full article