Exploring the Evolving Landscape of Stereotactic Body Radiation Therapy in Hepatocellular Carcinoma.

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.

Effects of electron density force to 1.0 and fill to 1.0 on VMAT treatment plans for lung SBRT.

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.

A lung SBRT treatment planning technique to focus high dose on gross disease.

This study investigated a straightforward treatment planning technique for definitive stereotactic body radiation therapy (SBRT) for patients with early-stage lung cancer aimed at increasing dose to gross disease by strategically penalizing the normal tissue objective (NTO) in the EclipseTM treatment planning system. Twenty-five SBRT cases were replanned to 50 Gy in 5 fractions using static and dynamic NTO methods (50 plans total). The NTO had a start dose of 100% at the target border, end dose of 20%, fall-off rate of 0.4/mm, and a priority of 150. For the static NTO plans, a lower planning target volume (PTV) objective was placed at 52 Gy with a priority of 100. Maximum dose was not penalized. Optimization was performed without user interaction. In contrast, the planner incrementally increased the priority of the NTO on the dynamic NTO plans until 95% of the target volume was covered by the prescription dose. Further, the dynamic NTO plans used both PTV lower and upper objectives at 63-64 Gy with priorities of 50. Maximum dose was penalized to ensure that the hot spot was within ± 2% of the static NTO global maximum dose. Following optimization, all plans were normalized so that the prescription dose covered 95% of the PTV. Plans were scored based on RTOG 0813 criteria, and dose to the internal target volume (ITV) and PTV was evaluated. The Wilcoxon signed-rank test (threshold = 0.05) was used to evaluate differences between the static and dynamic NTO plans. All plans met RTOG 0813 planning guidelines. In comparison to the static NTO plans, the dynamic NTO plans exhibited statistically significant increases in PTV mean dose, ITV mean dose, and PTV-ITV mean dose. Notably, the dynamic NTO plans more effectively concentrated the high dose on gross disease at the center of the PTV. As compared to the static NTO plans, the mean dose was 4.6 Gy higher in the ITV while only 1.3 Gy higher in the PTV-ITV rind of the dynamic NTO plans. Global maximum doses were similar. There were some small yet statistically significant differences in dose conformity between plan types. Furthermore, the dynamic NTO plans demonstrated a significant reduction in total monitor units (MU). This study demonstrated an efficient optimization strategy for lung SBRT plans that concentrates the highest dose in the gross disease, which may improve local control.

Patients With Surgically Resectable Lung Cancer Who Opt for Radiation Have Worse Outcomes.

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.

Lung SBRT: Dose gradient optimization based on target size.

This study investigated optimization settings that steepen the dose gradient as a function of target size for lung stereotactic body radiation therapy (SBRT). Sixty-eight lung SBRT patients with planning target volumes (PTVs) ranging from 2-203 cc were categorized into small (<20 cc), medium (20-50 cc), and large (>50 cc) groups. VMAT plans were generated using the normal tissue objective (NTO) to penalize the dose gradient at progressively steeper NTO fall-off values (0.1, 0.2, 0.3, 0.4, 0.5 mm-1). Dose was calculated using the AcurosXB algorithm and was normalized so the prescription dose covered 95% of the PTV. Mann-Whitney, Kruskal-Wallis and ANOVA tests were used to assess for statistical differences in the Conformity Index at the 50% isodose level (CI50%), global maximum dose (Dmax), and monitor units (MU) across the various NTO settings. All plans adhered to institutional criteria and met the guidelines of the Radiation Therapy Oncology Group 0813. Steeper NTO fall-off values significantly increased Dmax and MUs across all groups (p < 0.05). CI50% significantly differed with fall-off values in small (0.3 mm-1) and medium (0.2 mm-1) targets, indicating steeper NTO fall-off values improve CI50% for small and medium targets (p < 0.05). Large targets showed no significant CI50% difference across these fall-off values. As target size increases, the importance of fall-off values in achieving an acceptable CI50% diminishes. Smaller targets benefit from steeper fall-off values despite increased Dmax and MUs. Consideration of fall-off value relative to target size is crucial to limit dose spillage outside the target.

Stereotactic body radiation therapy (SBRT) in patients with hepatocellular cancer-a narrative review and expert opinion.

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.

Adrenal Insufficiency following Stereotactic Ablative Radiotherapy (SAbR) of Adrenal Gland Metastases.

BACKGROUND: Adrenal metastases are often treated with stereotactic ablative radiation (SAbR). We aimed to assess the incidence, timing, and factors associated with the development of primary adrenal insufficiency (PAI) following SAbR. METHODS: A retrospective cohort study comprised 66 consecutive patients (73% men, median age 61 years) who underwent SAbR for adrenal metastasis. RESULTS: The series encompassed metastases from renal cell carcinoma (41%), lung tumors (38%), colorectal adenocarcinoma (9%), melanoma (5%), and others (7%). Median follow-up was 17 months from SAbR. Nine (14%) patients developed PAI at a median of 4.3 months (range, 0.7-20.2). The incidence of PAI was 44% in patients with prior adrenalectomy receiving unilateral SAbR, 44% with bilateral SAbR, 2% with unaffected contralateral gland, and 0% with bilateral metastases treated with unilateral SAbR. PAI was associated with prior adrenalectomy (odds ratio [OR] 32) and bilateral SAbR (OR 8.2), but not age, sex, metastasis size, or biological effective dose. Post-SAbR 6-month and 1-year local control rates were 82% and 75%, respectively. CONCLUSIONS: Patients undergoing SAbR for adrenal metastasis are at high risk of developing PAI. PAI is associated with bilateral SAbR and contralateral adrenalectomy. PAI is unlikely with a remaining unaffected adrenal gland or in the setting of bilateral adrenal metastases with unilateral SAbR.

Oligometastatic Urothelial Cancer and Stereotactic Body Radiotherapy: A Systematic Review and an Updated Insight of Current Evidence and Future Directions.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is the most commonly used metastasis-directed therapy (MDT) for oligometastatic urothelial carcinoma (omUC). Despite efforts in defining this disease entity, open questions remain concerning the role of MDT and the use of biomarkers, imaging, and its combination with systemic therapies. The aim of the present systematic review is to provide an updated overview of the current clinical evidence on SBRT for omUC in terms of survival and local control benefits. We also aim to provide updates on controversial areas and future directions in this emerging field. METHODS: With a systematic approach, following PRISMA recommendations, we searched two databases to identify and select articles published up until March 2024 reporting the use of SBRT for omUC with or without concomitant systemic therapies. Prospective randomized or non-randomized studies as well as retrospective studies were included. RESULTS: Eight studies were selected for data extraction and 293 omUC patients treated with SBRT were collectively analyzed. In metachronous omUC patients, SBRT delivered with ablative doses (BED10 ≥ 78 Gy) was associated with a 2-year overall survival (OS) rate of 50.7% (95% CI 35.1-64.4%). The use of sub-ablative SBRT doses (BED10 = 43.2 Gy) in combination with immunotherapy did not demonstrate significant clinical outcome improvement in two prospective studies. The overall tolerance was good, with only one study reporting toxicity of grade 3 in up to 18% of the patients treated with SBRT in combination with immunotherapy. CONCLUSIONS: SBRT is an effective and widely available MDT option in omUC, although this is based on a limited number of studies. Despite the attempt to use SBRT as an immune response trigger in combination with immunotherapy, no significant improvement in survival outcomes has been observed. The integration of new systemic agents with MDT will likely define a new scenario for the treatment of omUC. The review protocol was registered in PROSPERO, ID: CRD42024522381.

Brachial plexopathy following stereotactic body radiation therapy in apical lung malignancies: A dosimetric pooled analysis of individual patient data.

BACKGROUND AND OBJECTIVES: The aim of this study is to establish dosimetric constraints for the brachial plexus at risk of developing grade ≥ 2 brachial plexopathy in the context of stereotactic body radiation therapy (SBRT). PATIENTS AND METHODS: Individual patient data from 349 patients with 356 apical lung malignancies who underwent SBRT were extracted from 5 articles. The anatomical brachial plexus was delineated following the guidelines provided in the atlases developed by Hall, et al. and Kong, et al.. Patient characteristics, pertinent SBRT dosimetric parameters, and brachial plexopathy grades (according to CTCAE 4.0 or 5.0) were obtained. Normal tissue complication probability (NTCP) models were used to estimate the risk of developing grade ≥ 2 brachial plexopathy through maximum likelihood parameter fitting. RESULTS: The prescription dose/fractionation schedules for SBRT ranged from 27 to 60 Gy in 1 to 8 fractions. During a follow-up period spanning from 6 to 113 months, 22 patients (6.3 %) developed grade ≥2 brachial plexopathy (4.3 % grade 2, 2.0 % grade 3); the median time to symptoms onset after SBRT was 8 months (ranged, 3-54 months). NTCP models estimated a 10 % risk of grade ≥2 brachial plexopathy with an anatomic brachial plexus maximum dose (Dmax) of 20.7 Gy, 34.2 Gy, and 42.7 Gy in one, three, and five fractions, respectively. Similarly, the NTCP model estimates the risks of grade ≥2 brachial plexopathy as 10 % for BED Dmax at 192.3 Gy and EQD2 Dmax at 115.4 Gy with an α/ß ratio of 3, respectively. Symptom persisted after treatment in nearly half of patients diagnosed with grade ≥2 brachial plexopathy (11/22, 50 %). CONCLUSIONS: This study establishes dosimetric constraints ranging from 20.7 to 42.7 Gy across 1-5 fractions, aimed at mitigating the risk of developing grade ≥2 brachial plexopathy following SBRT. These findings provide valuable guidance for future ablative SBRT in apical lung malignancies.

Comparison between Trans-Arterial Chemoembolization Followed by Stereotactic Body Radiation Rherapy and Trans-Arterial Chemoembolization Alone in BCLC Stage B Hepatocellular Carcinoma: A Pilot Study.

OBJECTIVE: Both Stereotactic Body Radiation Therapy (SBRT) and Trans-arterial Chemoembolization (TACE) are now being widely used to treat advanced hepatocellular carcinoma (HCC) and can improve tumor local control rates. We aimed at evaluating the efficacy and toxicity of combining SBRT and TACE in comparison to TACE alone in unresectable HCC. METHODS: 42 unresectable Barcelona Clinic Liver Cancer (BCLC) stage B HCC Child Pugh (CP) A patients were randomized to receive either: TACE alone (Arm A) or TACE followed by SBRT (Arm B). Dose prescribed was 40Gy in 5consecutive daily fractions over 1 week . We compared the local control (LC), Progression free survival (PFS), overall survival (OS) and toxicity between the two arms. RESULTS: 22 patients were in arm A versus 20 patients in arm B with median follow up 20 months starting recruitment from April 2021 till January 2023. Both LC, PFS were significantly better in Arm B. Complete remission (CR) rate was 54.5% and 75% in Arm A and B, respectively. Median PFS was 16 months in Arm B compared to 11 months in Arm A (p =0.003). Median OS was not reached in both arms. Both arms had comparable toxicities. CONCLUSION: Adding SBRT to TACE in advanced HCC, is safe and feasible with better efficacy in terms of LC and PFS with comparable side effects, in comparison to TACE alone.

Stereotactic body radiotherapy using CyberKnife versus interstitial brachytherapy in accelerated partial breast irradiation on left-sided breast: A comparison of dosimetric characteristics and preliminary clinical results.

INTRODUCTION: We compared the dosimetric characteristics of the target and organs at risk (OARs) as well as the preliminary clinical outcomes between two accelerated partial breast irradiation (APBI) techniques. METHODS: Forty-four patients diagnosed with left-sided early breast cancer who underwent APBI using either interstitial brachytherapy (IB) or stereotactic body radiation therapy (SBRT) with CyberKnife (CK) were retrospectively reviewed. The dosimetric parameters of the target and OARs were compared. Preliminary clinical outcomes, including tumor control and acute toxicity, were analyzed. RESULTS: Treatment plans with CK demonstrated a better cardiac dose-sparing effect. Radiation doses to the heart at V150cGy for the CK and IB groups were 24.4 % and 60.4 %, respectively (p < 0.001), while the mean heart doses for the CK and IB groups were 107.4 cGy and 204 cGy, respectively (p < 0.001). The heart D1c.c. and the ipsilateral lung received a lower dose in the IB group, without any significant differences. The median follow-up time in the CK and IB groups was 28.6 and 61.3 months, respectively. No patients died from either breast cancer or cardiac events during follow-up. A locoregional recurrence event at the neck occurred in one patient within the IB group. CONCLUSIONS: APBI planned by CK was shown to have a better dose-sparing effect on the heart, as well as better conformity and homogeneity to the target. CK is a non-invasive treatment which showed minimal acute toxicity and promising tumor control.

Development and validation of a prognostic nomogram in patients aged ≥65 years with stage I-II non-small cell lung cancer treated with stereotactic body radiotherapy.

INTRODUCTION: This study aims to discern the efficacy and toxicity of stereotactic body radiotherapy (SBRT) in older adults with stage I-II non-small cell lung cancer (NSCLC) and establish a prognostic nomogram for these patients. MATERIALS AND METHODS: One hundred forty-two patients (aged ≥65 years) with clinically-confirmed stage I-II NSCLC treated with SBRT from 2009 to 2020 were enrolled in the study. Primary end points included overall survival (OS), progression free survival (PFS), cumulative incidences of local failure (LF), regional failure (RF), distant failure (DF), and toxicity. A nomogram for OS was developed and validated internally using one thousand bootstrap resamplings. RESULTS: The median times to LF, RF, and DF were 22.1 months, 26.9 months and 24.1 months, respectively. The 1-, 3-, and 5-year PFS rates from the start of SBRT were 79.4 %, 53.1 %, and 38.9 %, respectively. Performance status, pre-SBRT platelet to lymphocyte ratio (PLR), and planning tumor volume (PTV) were predictive of PFS. The 1-, 3-, and 5-year OS rates from the start of SBRT were 90.8 %, 67.9 % and 47.6 %, respectively. In multivariate analysis, good performance status, a low level of pre-SBRT PLR, and small tumor size were associated with better prognosis, all of which were included in the nomogram. The model showed optimal discrimination, with a C-index of 0.651 and good calibration. The most common adverse reactions were grade 1-2, such as anemia, cough, and fatigue. DISCUSSION: SBRT is a reasonable treatment modality for early-stage NSCLC in older adults. It achieved good survival outcomes and low toxicity. The proposed nomogram may be able to estimate individual outcomes for these patients.

Stereotactic body radiation therapy for colorectal cancer liver metastases.

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.

Stereotactic body radiation therapy in non-liver colorectal metastases: a scoping review.

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.

Secondary Cancer in Prostate Cancer Patients Treated With Advanced External Beam Radiation Therapy.

Purpose: Previous studies have shown that external beam radiation therapy is associated with an increased risk of second primary cancer (SPC) among prostate cancer (PCa) patients, but the relative risks associated with newer and advanced radiation modalities such as proton beam therapy (PBT) and stereotactic body radiation therapy (SBRT) are unclear. This study aimed to assess the relative probability of SPC among patients treated with these newer modalities compared to intensity-modulated radiation therapy (IMRT). Patients and Methods: Using the National Cancer Database (NCDB), N0M0 PCa cases diagnosed between 2004 and 2018 were identified. Second primary cancer probabilities were compared among those treated with curative-intent PBT, SBRT, and IMRT. Multivariable logistic regression and inverse probability of treatment weighting were used to generate adjusted odds ratios (aORs) and 95% confidence intervals (CIs). Results: In total, 133 898 patients were included, with a median age of 69 years and median follow-up of 6.4 years. As their first course of treatment, 3420 (2.6%) received PBT, 121 211 (90.5%) received IMRT, and 9267 (6.9%) received SBRT. Compared with IMRT, PBT and SBRT were associated with lower SPC risk (aORs and 95% CIs, PBT: 0.49 [0.40-0.60], SBRT: 0.57 (0.51-0.63), P < .001). Inverse probability of treatment weighting analyses corroborated these results. Conclusion: In this large national cohort, PBT and SBRT performed similarly and were associated with reduced SPC risk compared to IMRT when used as the first course of treatment.

Prognostic value of circulating tumor cells in oligorecurrent hormone-sensitive prostate cancer patients undergoing stereotactic body radiation therapy.

BACKGROUND: Stereotactic body radiation therapy (SBRT) is an effective metastasis-directed therapy for managing oligometastatic prostate cancer patients. However, it lacks reliable biomarkers for risk stratification. Circulating Tumor Cells (CTC) show promise as minimally invasive prognostic indicators. This study evaluates the prognostic value of CTC in oligorecurrent hormone-sensitive prostate cancer (orHSPC). METHODS: orHSPC patients with 1-3 nodal and/or bone metastases undergoing SBRT were enrolled (N = 35), with a median follow-up time of 42.1 months. CTC levels were measured at baseline (T0), 1 month (T1), and 3 months (T2) post-SBRT using a novel metabolism-based assay. These levels were correlated with clinical outcomes through Cox-regression and Kaplan-Meier analyses. RESULTS: Median CTC counts were 5 at T0, 8 at T1, and 5 at T2 with no significant variation over time. Multivariate analysis identified high (≥5/7.5 mL) T0 CTC counts (HR 2.9, 95% CI 1.3-6.5, p = 0.01, median DPFS 29.7 vs. 14.0 months) and having more than one metastasis (HR 3.9, 95% CI 1.8-8.6, p < 0.005, median DPFS 34.1 vs. 10.7 months) as independent predictors of distant progression-free survival (DPFS). CTC assessment successfully stratified patients with a single metastasis (HR 3.4, 95% CI 1.1-10.2, p = 0.03, median DPFS 42.1 vs. 16.7 months), but not those with more than one metastasis. Additionally, a combined score based on CTC levels and the number of metastases effectively stratified patients. CONCLUSION: The study demonstrates that hypermetabolic CTC could enhance risk stratification in orHSPC patients undergoing SBRT, particularly in patients with limited metastatic burden, potentially identifying patients with indolent disease who are suitable for tailored SBRT interventions.

DARES: A Phase II Trial of Durvalumab and Ablative Radiation in Extensive-Stage Small Cell Lung Cancer.

BACKGROUND: Immunotherapy in combination with chemotherapy is first-line treatment for patients with extensive-stage small-cell lung cancer (ES-SCLC). Growing evidence suggests that radiation, specifically stereotactic body radiation therapy (SBRT), may enhance the immunogenic response as well as cytoreduce tumor burden. The primary objective of the study is to determine the progression free survival for patients with newly diagnosed ES-SCLC treated with combination multisite SBRT and chemo-immunotherapy (carboplatin, etoposide, and durvalumab). METHODS: This is a multicenter, single arm, phase 2 study. Patients with treatment-naïve, ES-SCLC will be eligible for this study. Patients will receive durvalumab 1500mg IV q3w, carboplatin AUC 5 to 6 mg/mL q3w, and etoposide 80 to 100 mg/m2 on days 1 to 3 q3w for four cycles, followed by durvalumab 1500mg IV q4w until disease progression or unacceptable toxicity. Ablative radiation will be delivered 1 to 4 extracranial sites in 3 or 5 fractions, determined by location, during cycle 2. The primary endpoint is progression-free survival, measured from day 1 of chemoimmunotherapy. Secondary endpoints include grade ≥3 toxicity by CTCAE v5.0 within three months of RT, overall survival, response rate, time to second line systemic therapy, and time to new distant progression. CONCLUSIONS: Now that immunotherapy is an established part of ES-SCLC management, it is important to further optimize its use and effect. This study will investigate the progression-free survival of combined SBRT and chemo-immunotherapy in patients with ES-SCLC. In addition, the data from this study may further inform the immunogenic role of SBRT with chemo-immunotherapy, as well as identify clinical, biological, or radiomic prognostic features.

Stereotactic body radiotherapy is an alternative to radiofrequency ablation for single HCC ≤5.0 cm.

Background & Aims: Radiation therapy has been refined with increasing evidence of the benefits of stereotactic body radiation therapy (SBRT) in treating hepatocellular carcinoma (HCC). In this study, we aimed to evaluate whether SBRT could serve as an alternative to radiofrequency ablation (RFA) for small HCC with a single lesion ≤5.0 cm. Methods: Patients with a single HCC lesion ≤5.0 cm who received RFA or SBRT were included. Cumulative local/distant recurrence rate, progression-free survival, overall survival, adverse events and subsequent treatments after recurrence were analyzed. Results: A total of 288 patients receiving RFA (n = 166) or SBRT (n = 122) were enrolled. The baseline characteristics between the two groups were comparable. The cumulative local recurrence rate in the SBRT group was significantly lower than that in the RFA group (hazard ratio [HR] 0.30, 95% CI 0.16-0.57, p <0.001), especially for patients with tumours >2.0 cm (HR 0.20, 95% CI 0.08-0.50, p <0.001) or adjacent to major vessels (HR 0.29, 95% CI 0.13-0.66, p <0.001). Cumulative distant recurrence rate, progression-free survival and overall survival were not significantly different between the two groups (all p >0.050). Adverse events were mild and easily reversible. However, more patients in the SBRT group suffered from Child-Pugh score and total bilirubin increases. More treatment options after recurrence or progression might be available for patients in the RFA group compared to those in the SBRT group (p <0.001). Conclusions: Both RFA and SBRT were effective and safe for HCC with a single lesion ≤5.0 cm. SBRT could be an alternative treatment to RFA, especially for tumours >2.0 cm or adjacent to major vessels. Impact and implications: Stereotactic body radiation therapy (SBRT) may be used as an alternative treatment to thermal ablation for patients with BCLC stage A hepatocellular carcinoma (HCC) who are not candidates for surgical resection, including those with tumours >3 cm and those with 1 to 3 tumours. This study focused on HCC patients with a specific tumour burden, namely a single lesion ≤5.0 cm, demonstrating that SBRT could be an effective and safe alternative to radiofrequency ablation (RFA), especially for those with tumours >2.0 cm or adjacent to major vessels. The findings of this study provided robust empirical evidence supporting the utilization of SBRT in treating small HCC, while also establishing a solid foundation for future prospective clinical investigations.

A novel predictor for dosimetry data of lung and the radiation pneumonitis incidence prior to SBRT in lung cancer patients.

Normal tissue complication probability (NTCP) models for radiation pneumonitis (RP) in lung cancer patients with stereotactic body radiation therapy (SBRT), which based on dosimetric data from treatment planning, are limited to patients who have already received radiation therapy (RT). This study aims to identify a novel predictive factor for lung dose distribution and RP probability before devising actionable SBRT plans for lung cancer patients. A comprehensive correlation analysis was performed on the clinical and dose parameters of lung cancer patients who underwent SBRT. Linear regression models were utilized to analyze the dosimetric data of lungs. The performance of the regression models was evaluated using mean squared error (MSE) and the coefficient of determination (R2). Correlational analysis revealed that most clinical data exhibited weak correlations with dosimetric data. However, nearly all dosimetric variables showed "strong" or "very strong" correlations with each other, particularly concerning the mean dose of the ipsilateral lung (MI) and the other dosimetric parameters. Further study verified that the lung tumor ratio (LTR) was a significant predictor for MI, which could predict the incidence of RP. As a result, LTR can predict the probability of RP without the need to design an elaborate treatment plan. This study, as the first to offer a comprehensive correlation analysis of dose parameters, explored the specific relationships among them. Significantly, it identified LTR as a novel predictor for both dose parameters and the incidence of RP, without the need to design an elaborate treatment plan.