Stereotactic Ablative Body Radiotherapy Research Articles

18F-FDG PET/CT biomarkers as predictors of long term outcomes and survival rates in patients with high risk malignant pulmonary masses/nodules treated with stereotactic ablative radiotherapy.

Stereotactic ablative body radiotherapy (SABR) is a standard treatment option for patients with malignant pulmonary masses (including primary and metastatic lesions) who are unfit for surgery or who are medically operable but refuse surgery. Flourine-18 flurodeoxyglucose positron emission tomography (18F-FDG PET) volumetric metabolic parameters, i.e., metabolic tumour volume (MTV) and total lesion glycolysis (TLG) play an important role in assessing the biological characteristics of some tumours and its role as potential prognostic factors has also been introduced. The aim of this retrospective study is to assess the value of baseline metabolic volumetric parameters as prognostic imaging biomarkers in patients with pulmonary masses/nodules treated with SABR. 70 patients were included in this retrospective study (39 male and 31 female, age range 47-91years, mean 76years). Standardized uptake value (SUVmax), SUVmean, MTV and TLG for all the patients were calculated on baseline 18F-FDG PET/CT. Patient outcome was divided into 3 categories free of disease, stable disease and disease progression. There was no significant statistical difference in the SUVmax and SUVmean in all the three categories. Mean SUVmax ranges from 7.13 to 8.08 with its highest value in the stable disease and lowest value in the progressive disease categories. Similarly, the average SUVmean was 4.9 in the free of disease category and 4.68 in the progressive disease category. MTV and TLG were low in the free of disease and the highest in progressive disease. MTV increased from 2.25 cm3 in free of disease category to 3.23 cm3 and 7.29 cm3 in stable disease and progressive disease, respectively. TLG has increased from 11.7 in the disease-free survival category to 18.77 and 40.39 in the stable and progressive disease, respectively. Patients with low MTV had longer overall survival (OS) than patients with high MTV (37months versus 27months, p value = 0. 0018). In addition, OS was longer in patients with low TLG (36months versus 24months, p value = 0.016). TLG and MTV are more useful than SUVmax and SUVmean for predicting outcome, OS and progression-free survival (PFS) in patients receiving SABR. The TLG and MTV measurement on 18F-FDG PET imaging may be routinely recommended in baseline 18F-FDG PET/CT prior to SABR.

Patient, tumour, and dosimetric factors influencing survival in non-small cell lung cancer patients treated with stereotactic ablative body radiotherapy.

We aimed to analyse clinical outcomes of peripheral, early-stage non-small cell lung cancer (NSCLC) patients treated with stereotactic ablative body radiotherapy (SABR), and evaluate potential patient, tumour, and dosimetric variables influencing survival. Data were collected retrospectively from patients treated between September 2012 and December 2016 and followed up until January 2021. Patient demographics, tumour characteristics, SABR dosimetric parameters, and survival data were collected from electronic patient medical records. Descriptive statistics were performed, and SPSS software was used for survival analysis. Eighty-nine patients were included of whom 49.5% were male and 50.5% female. Median age was 74 years. 98.8% of patients had T1-2 tumours and 89.9% underwent 55 Gy in 5 fractions. Median overall survival time was 58.7 months. On uni- and multi-variate analysis, neither patient nor tumour variables showed association with overall survival. However, planning target volume (PTV) and minimum dose to PTV correlated with overall survival. There was a signal for association between mean lung dose and overall survival on multivariate analysis. Our long-term results show SABR is an effective treatment for peripheral, early-stage NSCLC with excellent overall survival, comparable to other series. Our study found only the PTV and minimum dose to PTV had an impact on overall survival, which demonstrates the importance of generating optimal SABR plans. Our work identified lung SABR dosimetric parameters that correlate with survival, which illustrates the importance of producing optimal lung SABR plans.

Is an all-phase ITV (internal target volume) a gold standard in the target definition of hepatocellular carcinoma?

Stereotactic ablative body radiation (SABR) is a well-recognized treatment option for hepatocellular carcinoma (HCC). Due to the inherent motion of liver tumors, effective motion management is crucial for successful SABR. In the motion-encompassing motion management technique, all 10 respiratory phase image datasets are delineated and designated as the internal target volume (ITV). Some treatment centers use single or combination image sets to delineate the target volume. This study determines which specialty image set most closely matches an all-phase ITV contour on a synchronized contrast-enhanced 4DCT. Synchronized 4DCT contrast and delayed scans were acquired for 10 patients in the study. The maximum intensity projection (MiP), average intensity projection (AvgIP), and minimum intensity projection (MinIP) images were generated. The ITV delineation was done in all 10 phases (ITV_all_phase). The ITV_2phase combines the peak inhale and exhale phase, ITV_2M combines MiP and MinIP, and ITV_3M combines MiP, MinIP, and AvgIP. All ITVs were compared to ITV_all_phase with Dice similarity index (DSI) and volumes. Using ITV_all_phase as the reference, the DSI and the mean ITV volumes for the different ITVs were as follows: ITV_all_phase (1 and 116.69 cc), ITV_2phase (0.87 and 105.27 cc), MiP (0.76 and 98.24 cc), AvgIP (0.72 and 94.54 cc), ITV_MinIP (0.67 and 81.08 cc), ITV_2M (0.84 and 106.26 cc), and ITV_3M (0.86 and 112.51 cc). The study demonstrates that in the motion-encompassing technique of motion management, the target volume generated by delineating all phases of 4DCT provides the most accurate representation for patients with HCC. Specialty image sets and their combinations, while sometimes close, tend to result in less accurate targeting. Hence, the all-phase 4DCT method should be preferred to avoid geographical misses and ensure optimal treatment outcomes. However, our conclusion may be limited by the technique we employed.

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

Background and objectivesThe 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 MethodsIndividual 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. ResultsThe 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/β ratio of 3, respectively. Symptom persisted after treatment in nearly half of patients diagnosed with grade ≥2 brachial plexopathy (11/22, 50 %). ConclusionsThis 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.

Effect of Treatment Delivery Schedule for Patients With Early-Stage Non-Small Cell Lung Cancer Treated With Stereotactic Ablative Radiation Therapy: A Population-Based Analysis

PurposeThe optimal stereotactic ablative body radiotherapy (SABR) delivery schedule in stage I non-small cell lung cancer (NSCLC) remains unclear. This population-based study investigated grade ≥ 2 toxicity rates, local failure (LF), and overall survival (OS) in patients treated with 48 Gy in 4 fractions scheduled every other day (QOD) versus daily with weekends (QDW) and consecutive daily without weekends (QD). Materials and MethodsBetween January 2019 and June 2022, treatment records using 48 Gy in 4 fractions were extracted from a provincial cancer registry and grouped by delivery as QOD, QDW, or QD. Toxicity events were recorded using CTCAE v5.0. The Kaplan-Meier method was used to compute OS while LF was calculated using cumulative incidence methods with death as a competing risk. Cox regression analyses and Fine-Gray modelling was used to assess for variables associated with OS and LF, respectively. ResultsOf 404 patients meeting study criteria, 190, 111, and 103 received QOD, QDW, and QD SABR, respectively. More patients receiving QDW SABR were medically inoperable and more patients receiving QD SABR had tumors abutting the chest wall. Median follow-up was 29.5 months (interquartile range [IQR] 19.2-38.4). Overall toxicity was low, with crude rates of acute and late grade ≥ 2 toxicity not being statistically different among the groups. No grade 4 or 5 toxicities were recorded. LF rates at 24 months were not different at 7.5% (95% confidence interval [CI] 3.7-11.3), 9.5% (95% CI 3.9-15.1), and 11.0% (95% CI 4.9-17.2) for the QOD, QDW, and QD groups, respectively (p = 0.60). QDW and QD schedules were not associated with LR. Similarly, no significant differences in median OS were found among the QOD, QDW, and QD groups at 47.5 months (95% CI 39.26-55,74), 52.7 (95% CI 34.7-70.7), and 49.0 months (95% CI 31.6-66.4), respectively. QDW and QD schedules were not associated with OS. ConclusionsThis population-based study demonstrated no statistically significant differences in grade ≥ 2 toxicity rates, LF, and OS for stage I NSCLC patients treated with lung SABR using 48 Gy in 4 fractions delivered QOD, QDW, and QD. Patient convenience and optimization of resources may be considered when choosing a lung SABR treatment delivery schedule.

37 the Management of Stage I Non-Small Cell Lung Cancer (NSCLC) in Ontario: A Population-Based Study of Practice Patterns of Care and Stereotactic Ablative Body Radiotherapy Utilization from 2010-2019

37 the Management of Stage I Non-Small Cell Lung Cancer (NSCLC) in Ontario: A Population-Based Study of Practice Patterns of Care and Stereotactic Ablative Body Radiotherapy Utilization from 2010-2019

1657TiP The STAMPEDE2 stereotactic ablative body radiotherapy (SABR) trial: A phase III, randomised, open-label trial in patients with newly diagnosed oligometastatic prostate cancer (PC) starting androgen deprivation therapy (ADT)

1657TiP The STAMPEDE2 stereotactic ablative body radiotherapy (SABR) trial: A phase III, randomised, open-label trial in patients with newly diagnosed oligometastatic prostate cancer (PC) starting androgen deprivation therapy (ADT)

Salvage stereotactic ablative body radiotherapy after thermal ablation of primary kidney cancer.

To evaluate the effectiveness and safety of salvage stereotactic ablative body radiotherapy (SABR) for recurrent renal cell carcinoma (RCC) after thermal ablation (TA). This study was a multi-institutional retrospective analysis of patients with recurrent RCC following TA who received SABR between 2016 and 2020. The primary study outcome was freedom from local failure, evaluated radiographically based on Response Evaluation Criteria in Solid Tumours (RECIST) v1.1. Distant failure, cancer-specific survival (CSS), overall survival (OS), treatment-related toxicity and renal function changes following SABR were the secondary outcomes. The Kaplan-Meier method was used to estimate freedom from local and distant failure, CSS and OS. Seventeen patients with 18 biopsy-confirmed RCCs were included, with a median (interquartile range [IQR]) age at time of SABR of 75.2 (72.6-68.7) years, a median (IQR) tumour size of 3.5 (1.9-4.1) cm and follow-up (reverse Kaplan-Meier method) of 3.36 (95% confidence interval [CI] 1.6-4.1) years. Six of the 17 patients had a solitary kidney. Five patients had failed repeat TA prior to SABR. The median (IQR) time from TA procedure to SABR was 3.03 (1.5-5.1) years. No patient experienced local progression, with a local control rate of 100%. Four patients, two with baseline metastatic disease, experienced distant progression. The distant progression-free survival, CSS and OS at 3 years were 72.1% (95% CI 51.9%-100%), 92.3% (95% CI 78.9%-100%) and 82.1% (95% CI 62.1%-100%), respectively. The median (IQR) glomerular filtration rate before SABR was 58 (40-71) mL/min, and at last follow-up, it was 48 (33-57) mL/min. No patient experienced grade 3+ toxicity or went on to develop end-stage renal disease. The results showed that SABR appears to be an effective and safe salvage strategy in patients with recurrent RCC following TA.

Management of Unresectable Cholangiocarcinoma Using Modern Radiation Therapy Techniques

AbstractCholangiocarcinoma (CCA) is a malignancy of epithelial cells in the bile duct, categorized based on its anatomical location as intrahepatic, perihilar, or extrahepatic. It has a low prevalence of ∼1.6 cases per 100,000 people in the United States, but has a poor prognosis. All stages included, CCA has a 5-year survival rate of less than 10%. The preferred curative treatment for intrahepatic, perihilar, and extrahepatic CCA is surgical resection combined with systemic chemotherapy. However, resection is not always a viable option for many patients, as the disease is often discovered at the time of diagnosis to be either metastatic or locally advanced precluding surgical resection. In this setting, a variety of options can be used, one of which is radiation therapy (RT). The administration of RT has evolved tremendously over the past decades. Total doses given can be limited by a tumor's proximity to regional normal organs such as the liver, stomach, bile duct, and small and large bowel. When a CCA is unresectable, it is often in close proximity to radiosensitive organs. Delivering RT in this setting therefore requires precise delivery techniques. An emerging technique known broadly as stereotactic body radiation therapy (SBRT) or stereotactic ablative body radiation therapy gives a highly focused, often ablative, form of RT to a defined and specific target. Categorically, SBRT offers a quick and efficient management option, in some cases only one to three total treatments. This narrative reviews various applications of SBRT for cholangiocarcinoma including SBRT alone, SBRT with chemotherapy, SBRT with chemotherapy followed by a liver transplantation (orthotopic liver transplantation), and finally novel combinations of SBRT with immunotherapy.

A multi-centre retrospective study of long-term outcomes of spinal re-irradiation with SABR.

Stereotactic ablative body radiotherapy (SABR) is a highly conformal technique utilising a high dose per fraction commonly employed in the re-treatment of spinal metastases. This study sought to determine the safety and efficacy of re-irradiation with SABR to previously treated spinal metastases. This was a retrospective analysis of patients at three Australian centres who have undergone spinal SABR after previous spinal radiotherapy to the same or immediately adjacent vertebral level. Efficacy was determined in terms of rates of local control, while safety was characterised by rates of serious complications. Thirty-three spinal segments were evaluated from 32 patients. Median follow-up for all patients was 2.6 years, and median overall survival was 4.3 years. Eleven of 33 (33.3%) treated spinal segments had local progression, with a local control rate at 12 months of 71.4% (95% C.I. 55.2%-92.4%). Four patients (16.7%) went on to develop cauda equina or spinal cord compression. Thirteen out of 32 patients (40.6%) experienced acute toxicity, of which 12 were grade 2 or less. Five out of 30 spinal (16.7%) segments with follow-up imaging had a radiation-induced vertebral compression fracture. There was one case of radiation myelitis which occurred in a patient who had mediastinal radiotherapy with a treatment field which overlapped their prior spinal radiation. The patients in this study experienced long median survival, durable tumour control and high rates of freedom from long-term sequelae of treatment. These results support the use of SABR in patients who progress in the spine despite previous radiotherapy.

A randomised controlled trial of Standard Of Care versus RadioAblaTion in Early Stage HepatoCellular Carcinoma (SOCRATES HCC)

BackgroundTherapeutic options for early-stage hepatocellular carcinoma (HCC) in individual patients can be limited by tumor and location, liver dysfunction and comorbidities. Many patients with early-stage HCC do not receive curative-intent therapies. Stereotactic ablative body radiotherapy (SABR) has emerged as an effective, non-invasive HCC treatment option, however, randomized evidence for SABR in the first line setting is lacking.MethodsTrans-Tasman Radiation Oncology Group (TROG) 21.07 SOCRATES-HCC is a phase II, prospective, randomised trial comparing SABR to other current standard of care therapies for patients with a solitary HCC ≤ 8 cm, ineligible for surgical resection or transplantation. The study is divided into 2 cohorts. Cohort 1 will compromise 118 patients with tumors ≤ 3 cm eligible for thermal ablation randomly assigned (1:1 ratio) to thermal ablation or SABR. Cohort 2 will comprise 100 patients with tumors > 3 cm up to 8 cm in size, or tumors ≤ 3 cm ineligible for thermal ablation, randomly assigned (1:1 ratio) to SABR or best other standard of care therapy including transarterial therapies. The primary objective is to determine whether SABR results in superior freedom from local progression (FFLP) at 2 years compared to thermal ablation in cohort 1 and compared to best standard of care therapy in cohort 2. Secondary endpoints include progression free survival, overall survival, adverse events, patient reported outcomes and health economic analyses.DiscussionThe SOCRATES-HCC study will provide the first randomized, multicentre evaluation of the efficacy, safety and cost effectiveness of SABR versus other standard of care therapies in the first line treatment of unresectable, early-stage HCC. It is a broad, multicentre collaboration between hepatology, interventional radiology and radiation oncology groups around Australia, coordinated by TROG Cancer Research.Trial registrationanzctr.org.au, ACTRN12621001444875, registered 21 October 2021.

71 Stereotactic Ablative Radiotherapy Is a Safe and Feasible Treatment Option for Patients with Hepatocellular Carcinoma

Abstract Aim Stereotactic ablative body radiotherapy (SABR) is a highly focused radiation treatment that delivers an intense dose of radiation to a tumour whilst limiting exposure of surrounding tissues. SABR has been associated with improvement in survival and good rates of local control in non-surgical candidates with hepatocellular carcinoma (HCC). The aim of this study was to evaluate the outcomes of HCC patients treated with SABR after its introduction in a tertiary referral hepatobiliary centre. Method A total of 32 patients (median age 73 years {47 to 85}, 78% male) who received SABR for HCC liver lesions between July 2020 and August 2022 were retrospectively analysed. Patient, treatment, and follow-up details were obtained from online patient records and imaging. Results Overall Survival rate was 78% at a median follow-up of 12 months (range 4 to 30). Local control was achieved in 72%, while progression occurred in 31%. Median time to progression was 6 months (range 3 to 31). The rate of progression-free survival at 12 months was 62.5%. Only 31% reported toxicities. No patients in the study group experienced any Grade ³ 3 toxicities. Conclusions Our experience following the introduction of SABR for patients with HCC is that SABR is a viable, well-tolerated and effective treatment option in this patient group. Further research is warranted to examine the clinical benefits of combination treatment with SABR and other treatment modalities to maximise disease control in patients with both early and advanced HCC.

HDR brachytherapy versus robotic-based and linac-based stereotactic ablative body radiotherapy in the treatment of liver metastases – A dosimetric comparison study of three radioablative techniques

PurposeThe aim of our study was to compare dosimetric aspects of three radioablation modalities – direct high-dose-rate brachytherapy (HDR-BT) and virtually planned stereotactic body radiation therapy performed on CyberKnife (SBRTck) and Elekta Versa HD LINAC (SBRTe) applied in patients with liver metastases. Material and methodsWe selected 30 patients with liver metastases, who received liver interstitial HDR-BT and virtually prepared plans for SBRTck and SBRTe. In all the cases, the prescribed dose was a single fraction of 25 Gy. Treatment delivery time, doses delivered to PTV and organs at risk, as well as conformity indices, were calculated and compared. ResultsThe longest median treatment delivery time was observed in SBRTck in contrast to HDR-BT and SBRTe which were significantly shorter and comparable. HDR-BT plans achieved better coverage of PTV (except for D98%) in contrast to SBRT modalities. Between both SBRT modalities, SBRTck plans resulted in better dose coverage in Dmean, D50%, and D90% values compared to SBRTe without difference in D98%. The SBRTe was the most advantageous considering the PCI and R100%. SBRTck plans achieved the best HI, while R50% value was comparable between SBRTe and SBRTck. The lowest median doses delivered to uninvolved liver volume (V5Gy, V9.1Gy) were achieved with HDR-BT, while the difference between SBRT modalities was insignificant. SBRT plans were better regarding more favourable dose distribution in the duodenum and right kidney, while HDR-BT achieved lower doses in the stomach, heart, great vessels, ribs, skin and spinal cord. There were no significant differences in bowel and biliary tract dose distribution between all selected modalities. ConclusionsHDR-BT resulted in more favourable dose distribution within PTVs and lower doses in organs at risk, which suggests that this treatment modality could be regarded as an alternative to other local ablative therapies in carefully selected patients’ with liver malignancies. Future studies should further address the issue of comparing treatment modalities in different liver locations and clinical scenarios.

Remineralization of lytic spinal metastases after radiation therapy – A retrospective cohort study comparing conventional external beam radiation therapy with stereotactic ablative body radiation

IntroductionOsteolytic spinal metastases (SM) have a higher risk of fracture. In this study we aim to confirm the remineralization of lytic SM after radiation therapy. Secondary the influence of SBRT compared to cEBRT and tumor type will be analyzed. MethodsA retrospective cohort study was performed. Results87 patients, 100 SM were included. 29 received SBRT, 71 cEBRT. Most common primary tumors were breast (35 %), lung (26 %) and renal (11 %). Both cEBRT and SBRT resulted in a significant increase of bone mineral density (BMD) (83.76 HU ± 5.72 → 241.41 HU ± 22.58 (p < 0.001) and 82.45 ± 9.13 → 179.38 ± 47.83p = 0.026). There was a significant increase in absolute difference of BMD between the SM and reference vertebrae (p < 0.001). There was no significant difference between SBRT and cEBRT. There was no increase of BMD in renal lytic SM after radiation therapy (pre-treatment: 85.96 HU ± 19.07; 3 m 92.00 HU ± 21.86 (p = 0.882); 6 m 92.06 HU ± 23.94 (p = 0.902); 9 m 70.44 HU ± 7.45 (p = 0.213); 12 m 98.08 HU ± 11.24 (p = 0.740)). In all other primary tumors, a significant increase of BMD after radiation therapy was demonstrated (p < 0,05). ConclusionWe conclude that the BMD of lytic SM increases significantly after radiation therapy. Lytic SM of primary renal tumors are the exception; there is no significant remineralization of renal lytic SM after radiation therapy. There is no benefit of SBRT over cEBRT in this remineralization. These findings should be taken into account when deciding on surgery in the potentially unstable group defined by the spinal instability neoplastic score.

Durvalumab and stereotactic ablative body radiotherapy (SABR) in locally advanced (LA) and borderline resectable (BR) pancreatic cancer (PDAC): Long-term outcomes and correlative insights.

4174 Background: Immune checkpoint blockade (ICB) has limited activity in genomically unselected patients (pts) with PDAC. While anti-tumor activity with combination SABR/ICB has been shown, biomarkers of response are poorly defined. We conducted a phase 1/2 study of PD-L1 inhibitor Durvalumab (D) and SABR after induction chemotherapy in LA and BR PDAC (NCT03245541). We report long-term outcomes and correlative biospecimen analyses. Methods: A multi-institutional, single arm phase 1/2 trial was conducted at Cedars-Sinai and Memorial Sloan Kettering. Initial clinical data reported by Tuli et al, ASCO 2023. Pre-treatment tissue assessed for p40 and GATA3 to determine classical vs basal subtype by immunohistochemistry. Tissue interrogated by immunofluorescence for PD-L1 expression and infiltration of immune cell subsets. Multiparametric immunophenotyping of peripheral blood mononuclear cells (PBMCs) by flow cytometry conducted on baseline and on treatment samples. Wilcoxon rank sum test used to determine difference in biomarkers from each timepoint; p-value &lt;0.05 significant. Results: N= 36 enrolled from 08/2017-05/2022; N=31(86%) LA, N=5 (14%) BR. N= 9 (25%) underwent resection; all R0. At median follow up 36.5 months, 6- and 12-month PFS 69%, 36%. Median PFS 8.7m (95% CI 6.1-14), median OS 16m (95% CI 13-26). N=2 (6%) alive without disease progression. Correlative analyses summarized (table). Key findings; Classical/basal subtyping feasible on N=9 (8 classical, 1 basal). Median PD-L1 score not associated with survival. Peri-tumoral, but not intratumoral CD8+ cells associated with PFS &gt;6 months. Flow cytometry feasible for 70 samples from N=35. Frequency of pre-treatment non-naïve CD4+ FoxP3+ Treg associated with PFS &gt;12. CD103+ CD8+ T Cells significantly expanded on treatment only in patients with PFS&gt;12m (p=0.038) and were significantly enriched relative to PFS&lt;12m on treatment. Conclusions: A proportion of pts with LA PDAC achieve durable control with D and SABR after induction chemotherapy. Baseline peri-tumoral CD8+ cells and peripheral CD103+ CD8 T cells and CD4+ Treg in PBMCs at baseline and on treatment may predict for benefit. Further analyses ongoing and validation in larger cohorts is warranted. Clinical trial information: NCT03245541 . [Table: see text]

Monocyte/lymphocyte ratio to predict immunoradiotherapy response in patients with advanced pretreated sarcoma.

e23523 Background: Immuno-radiotherapy may improve outcomes for patients with advanced solid tumors, although optimized combination modalities remain unclear. Here, we report the sarcoma cohort analysis from the SABR-PDL1 trial that evaluated the PD-L1 inhibitor atezolizumab in combination with stereotactic body radiation therapy (SBRT) in patients with advanced cancer. Methods: Eligible patients received atezolizumab 1200 mg every 3 weeks until progression or unmanageable toxicity, together with ablative SBRT delivered concurrently with the 2nd cycle (recommended dose of 45 Gy in 3 fractions, adapted upon normal tissue tolerance constraint). SBRT was delivered to at least one tumor site, with at least one additional measurable lesion being kept from the radiation field. The primary efficacy endpoint was one-PFS rate from the start of atezolizumab. Sequential tumor biopsies were collected for deep multi-feature immune profiling and monocyte/lymphocyte ratio (sum of cells derived from the monocytic lineage including monocytes, macrophages and myeloid dendritic cells, divided by sum of lymphocytes) were computed both on tumor and blood. Results: 61 highly pretreated (median of 5 prior lines) patients with advanced sarcomas (leiomyosarcoma: 28% and other types; 32 men [53%]; median age, 47 years [range, 37-55 years]) were enrolled in two centers (France; Spain) from 03/2020 to 04/2021. All but one received atezolizumab and 56/61 (92%) received SBRT. The most frequently irradiated site was lung (n = 36/72 lesions; 50%). Treatment-related G3 (no G4-5) toxicity was observed in one (2%) patient. Median OS and PFS were respectively 12.2 [95%CI:7-18.4] and 2.5 months [95%CI:1.2-2.6], including five (8.2%) patients with PFS &gt; 1 year. Best overall responses consisted of PR (n = 3;5%) and SD (n = 36; 60%). Altogether, 182 (n = 86 paraffin; n = 96 freshly frozen) sequential tumor biopsies from 35 patients were successfully analyzed. None (0%) of the biopsies harbored tertiary-lymphoid structures. Tumor RNA sequencing analysis using independent immune deconvolution technics including CIBERSORTabs, EPIC and xCELL revealed an increased tumor infiltration of monocytic lineage-derived cells in patients who rapidly progressed. Differential gene expression analysis showed a significant upregulation of genes implicated in immunosuppression in unressponsive tumors. Unresponsive tumors were enriched with immune chemoattractants. We found higher monocyte/lymphocyte ratio in unresponsive patients compared to patients who had stable disease or tumor response both in the tumor and in the blood. Matched blood and tumor monocyte/lymphocyte ratios were significantly correlated in this population. Conclusions: This study provides new data on the feasibility, efficacy, and immune context of tumors that may help identifying patients with advanced sarcomas most likely to respond to immuno-radiotherapy. Clinical trial information: NCT02992912 .

Stereotactic body radiation therapy for primary renal cell carcinoma: A review on behalf of the CC-AFU

IntroductionThe incidence of localized renal cell carcinoma (RCC) is on the rise among individuals aged 70 and older. While the gold standard for treatment remains surgical resection, some elderly and frail patients with comorbidities are not eligible for this procedure. In selected cases, percutaneous thermal ablation, such as cryotherapy, microwave and radiofrequency, offers less invasive options. General anesthesia is sometimes necessary for such treatments, but most of the procedures can be conducted using mild or deep conscious sedation. This approach is preferably recommended for small cT1a tumors situated at a distance from the renal hilum and/or ureter. Active surveillance remains an alternative in the case of small low grade RCC although it may induce anxiety in certain patients. Recent research has highlighted the potentials of stereotactic ablative body radiotherapy (SABR) as a noninvasive, well-tolerated, and effective treatment for small renal tumors. This narrative review aims to explore recent advances in SABR for localized RCC, including appropriate patient selection, treatment modalities and administration, as well as efficacy and tolerance assessment. Material and methodsWe conducted a literature review using the terms [kidney cancer], [renal cell carcinoma], [stereotactic radiotherapy], [SBRT], and [SABR] in the Medline, PubMed, and Embase databases, focusing on prospective and relevant retrospective studies published in English. ResultsStudies report local control rates ranging from 70% to 100% with SABR, highlighting its efficacy in treating RCC. The decline in glomerular filtration rate (GFR) is approximately −5 to −17mL/min over the years following SABR. Common toxicities are rare, primarily CTCAE grade 1, include fatigue, nausea, chest or back pain, diarrhea, or gastritis. ConclusionStereotactic ablative body radiotherapy (SABR) may be considered as a viable option for patients with localized RCC who are not suitable candidates for surgery with a high local control rate and a favorable safety profile. This approach should be discussed in a multidisciplinary meeting and results from ongoing clinical trials are awaited. Level of evidence5.

Prospective phase II trial on ablative stereotactic body radiation therapy (SBRT) for medically inoperable thoracic nodes metastases

BackgroundOligometastases in mediastinal nodes are increasingly prevalent, posing challenges for treatment with stereotactic body radiotherapy (SBRT) due to proximity to organs at risk (OARs). We report the results of a single prospective observational phase II trial on ablative SBRT for medically inoperable thoracic nodes metastases (NCT02970955). Material and methodsSince 2017, patients with < 3 nodal metastases were evaluated by the tumor board and included if deemed inoperable. SBRT was delivered using risk adaptive approach based on number, site and size of metastatic nodes (50 Gy/5fractions, 60 Gy/8fractions, 70 Gy/10 fractions). Planning target volume (PTV) partial underdosage was allowed. The primary end point was local control (LC) at 12 months. Secondary end points were: acute and late toxicities, overall survival (OS), progression free survival (PFS), and time to next systemic therapy (TTNS). ResultsBetween 03/2017–11/2021, 32 patients (41 nodal metastases) were included. NSCLC (13pts), breast (5pts) and colorectal cancer (4pts) were the most represented primary tumour. In 66 % cases, partial PTV undercoverage was necessary. LC at 1 and 2 years was 93.5 % and 82.3 %, respectively. Treatment was well-tolerated with no acute or late toxicity ≥ G3. Median OS was 59.7 months. OS at 1 and 2 years was 96.9 % and 83.8 % respectively. Median PFS was 12.2 months. PFS at 1 and 2 years was 53.1 % and 31.3 %, respectively. ConclusionThis trial supported the feasibility and safety of ablative SBRT for thoracic nodes metastases thanks to risk adaptive approach allowing to delay of new systemic therapies. Larger studies are needed to confirm these observations.

Functional imaging guided stereotactic ablative body radiotherapy (SABR) with focal dose escalation and bladder trigone sparing for intermediate and high-risk prostate cancer: study protocol for phase II safo trial

BackgroundStereotactic ablative body radiotherapy (SABR) is an emerging treatment alternative for patients with localized low and intermediate risk prostate cancer patients. As already explored by some authors in the context of conventional moderate hypofractionated radiotherapy, focal boost of the index lesion defined by magnetic resonance imaging (MRI) is associated with an improved biochemical outcome. The objective of this phase II trial is to determine the effectiveness (in terms of biochemical, morphological and functional control), the safety and impact on quality of life, of prostate SABR with MRI guided focal dose intensification in males with intermediate and high-risk localized prostate cancer.MethodsPatients with intermediate and high-risk prostate cancer according to NCCN definition will be treated with SABR 36.25 Gy in 5 fractions to the whole prostate gland with MRI guided simultaneous integrated focal boost (SIB) to the index lesion (IL) up to 50 Gy in 5 fractions, using a protocol of bladder trigone and urethra sparing. Intra-fractional motion will be monitored with daily cone beam computed tomography (CBCT) and intra-fractional tracking with intraprostatic gold fiducials. Androgen deprivation therapy (ADT) will be allowed. The primary endpoint will be efficacy in terms of biochemical and local control assessed by Phoenix criteria and post-treatment MRI respectively. The secondary endpoints will encompass acute and late toxicity, quality of life (QoL) and progression-free survival. Finally, the subgroup of high-risk patients will be involved in a prospective study focused on immuno-phenotyping.DiscussionTo the best of our knowledge, this is the first trial to evaluate the impact of post-treatment MRI on local control among patients with intermediate and high-risk prostate cancer undergoing SABR and MRI guided focal intensification. The results of this trial will enhance our understanding of treatment focal intensification through the employment of the SABR technique within this specific patient subgroup, particularly among those with high-risk disease, and will help to clarify the significance of MRI in monitoring local responses. Hopefully will also help to design more personalized biomarker-based phase III trials in this specific context. Additionally, this trial is expected to be incorporated into a prospective radiomics study focused on localized prostate cancer treated with radiotherapy.Trial registrationClinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023.Trial SponsorIRAD/SEOR (Instituto de Investigación de Oncología Radioterápica / Sociedad Española de Oncología Radioterápica).Study settingClinicaltrials.gov identifier: NCT05919524; Registered 17 July 2023.Trial statusProtocol version number and date: v. 5/ 17 May-2023. Date of recruitment start: August 8, 2023. Date of recruitment completion: July 1, 2024.

Second Chance for Cure: Stereotactic Ablative Radiotherapy in Oligometastatic Disease.

Local ablative therapy, such as radiotherapy or surgery, plays a key role in treatment of patients with oligometastatic disease. Stereotactic ablative body radiotherapy (SABR) comes to the fore as a safe and effective treatment for patients with a limited number of metastases, even those located in hard-to-reach body sites. Many researchers have suggested that metastatsis-directed therapy could improve long-term progression-free survival (PFS) and overall survival (OS) in patients with oligometastases. This was a retrospective, single-arm, observational study conducted between July 2015 and February 2022. In our institute, 60 patients with controlled primary tumors and one to five metastases were treated with SABR. Prescribed radiation doses ranged from 12 to 60 Gy administered in one to seven fractions. We aimed to determine whether metastatic-directed therapy using SABR for all oligometastases affects OS and PFS and whether the primary tumor or metastatic site influences OS/PFS. The most common primary malignancy types were prostate (n = 14), colorectal (n = 10), lung (n = 7), and breast cancers (n = 6). The median follow-up was 30 months, ranging from 9 to 79. The 1-, 3-, and 5-year PFS and OS rates were 54.9%, 37.0%, and 37.0% and 98.3%, 84.4%, and 73.8%, respectively, and the median time to first progression was 15 (range, 2-32) months. Twenty-four (40%) patients had no recurrence. In our analysis, primary tumor site was not an independent prognostic factor. The metastatic site may influence on patient outcome in cases of localized bone and liver metastases. In our retrospective analysis, SABR was associated with favorable levels of PFS and OS in patients with oligometastases. The limitations of our study were lacking high-level evidence, and randomized studies to compare SABR and palliative standard of care are mandatory.